Evaluation and Charaterisation of the Thermal Grill Apparatus for Spinal … · 2013-11-01 ·...

EVALUATION AND CHARACTERISATION OF THE

THERMAL GRILL APPARATUS FOR SPINAL CORD

INJURY PATIENTS

by

Diane Kostka

A thesis submitted in conformity with the requirements for the

degree of Master of Health Science in Clinical Engineering

Graduate Department of Institute of Biomaterials and Biomedical Engineering

University of Toronto

©Copyright by Diane Kostka 2011

Evaluation and Characterisation of the Thermal Grill apparatus for Spinal Cord Injury patients | 2011

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Evaluation and Characterisation of the Thermal Grill apparatus for

Spinal Cord Injury patients.

Diane Kostka

Master of Health Science in Clinical Engineering

Institute of Biomaterials and Biomedical Engineering

University of Toronto

2011

Abstract

Patients suffering from central neuropathic pain have thermal sensory deficits within the painful

area. Prior research proposed that the loss of thermal sensation in regions of central neuropathic

pain may reflect similar central nervous system interaction between warm and cold sensory

inputs that underlie the Thermal Grill Illusion (TGI) in which burning pain is felt while reduced

warm/cold sensations are reported.

This work presents a portable and reliable device that was used to systematically evaluate the

characteristics of the TGI in healthy individuals. The results suggest that the spatial distribution

of the warm and cool stimuli significantly affected the quality of perceived TGI. Additionally,

simultaneous tactile and thermal stimulation was shown to be significantly less painful than

thermal stimulation alone. A high correlation was also seen in the subject‘s TG intensity scores

and their cold pain threshold. These results are useful for future TGI studies for central

neuropathic pain.


iii

Acknowledgements

I am deeply grateful to Dr. Milos Popovic for giving me the confidence to explore my research

interests and the guidance to avoid getting lost in my exploration. Dr. Popovic was a fabulous

advisor: cheery, perceptive, and mindful of the things that truly matter.

I am very grateful to my co-supervisor Dr. Judith Hunter. With her enthusiasm, inspiration, and

great efforts to explain things clearly and simply, she helped peak my interest in the study of

pain. Dr. Jonathan Dostrovsky‘s guidance and attention to my work consistently led me along the

correct path, and he threw enough research questions my way to allow me to consider my

research from many angles. I would also like to thank Dr. Carnahan Heather for taking the time

to sit on my advisory committee and for providing a fresh perspective on my research.

I am indebted to my many student colleagues at REL for providing a stimulating and fun

environment in which to learn and grow. I am especially grateful to Helen Zhang and Noel Wu

for their research help, insightful advice and time.

I am truly grateful to my parents for their endless help, understanding and support through the

last two years. Finally, Gaurav Jain for his constant support, enthusiasm and feedback, and

without whom this document would not have been possible.


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Table of Contents

Glossary ........................................................................................................................................ ix

Chapter 1:Introduction .................................................................................................................1

1.1 Motivation ..............................................................................................................................1

1.2 Hypothesized cause of CNP ...................................................................................................3

1.3 Roadmap of the Thesis ...........................................................................................................3

Chapter 2: Background .................................................................................................................5

2.1 Central Neuropathic Pain .......................................................................................................5

2.2 Central Neuropathic Pain and Spinal Cord Injury .................................................................6

2.3 Psychophysical Testing ..........................................................................................................7

2.4 Thermal Grill Illusion – Etiology ...........................................................................................9

2.5 TGI and Central Neuropathic Pain ......................................................................................11

2.6 Research Problem .................................................................................................................13

2.6.1 Thermal Grill Devices ...................................................................................................13

2.6.2 Research Methodology ..................................................................................................14

Chapter 3: Research Objective ...................................................................................................17

3.1 Objective ..............................................................................................................................17

3.2 Hypotheses ...........................................................................................................................18

Chapter 4: Methodology..............................................................................................................19

4.1 Thermal Grill Apparatus .....................................................................................................19

4.1.1 Hardware Design ...........................................................................................................20

4.1.2 Software Design ............................................................................................................24


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4.2 Subjects ................................................................................................................................28

4.3 Experimental Procedure .......................................................................................................29

4.3.1 Pre-Testing ....................................................................................................................30

4.3.2 Participant Feedback .....................................................................................................30

4.3.3 Determination of Thermal Thresholds ..........................................................................31

4.3.3.1 Uniform thermal stimulus .......................................................................................31

4.3.3.2 Thermal grill stimulus .............................................................................................32

4.3.4 Evaluation of optimal grill configurations ....................................................................32

4.3.5 Evaluation of dynamic thermal grill .............................................................................33

4.4 Order of Presentation ...........................................................................................................34

Chapter 5: Results........................................................................................................................35

5.1 Subjects ................................................................................................................................35

5.2 Thermal Thresholds – Spatial Characteristics ......................................................................35

5.3 Pain Elicited by the TG ........................................................................................................36

5.4 Static vs. Dynamic thermal testing Intensity ratings ............................................................37

5.5 Grill Configurations and TG intensity rating .......................................................................38

5.6 Thermal Quality and Characteristics of the TGI ..................................................................41

5.7 Thermal Thresholds and the TGI .........................................................................................44

5.8 Variance in Response ...........................................................................................................44

Chapter 6: Discussion ..................................................................................................................46

6.1 TGI as a Painful Experience .................................................................................................46

6.2 TG perception during Static vs. Dynamic Grill testing ........................................................47

6.3 Spatial Characteristics of the TG .........................................................................................48

6.4 Temporal Characteristics of the TG .....................................................................................49

6.5 TGI and Thermal Thresholds ...............................................................................................50


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6.6 The Stability of the TGI .......................................................................................................51

6.7 Important methodological issues ..........................................................................................51

6.8 Using the TG as a Research Tool .........................................................................................52

6.9 Limitations of this Study ......................................................................................................53

Chapter 7: Conclusions ...............................................................................................................55

References .....................................................................................................................................56

Appendices ....................................................................................................................................62

A. Screenshots of the User Interface ..........................................................................................62

B. Experiment Procedure Forms ................................................................................................63

C. Thermal Grill User Manual ...................................................................................................64

D. Study Script ...........................................................................................................................76


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List of Figures

2.1 Mechanism of the Thermal Grill Illusion ................................................................................11

2.2 Thermal Grill Stimulation Patterns ..........................................................................................16

4.1 Isometric 3-D view of the Thermal Grill device .....................................................................21

4.2 Mechanical Drawing of the thermal grill device ....................................................................21

4.3 Disturbance rejection ratio of device ......................................................................................23

4.4 Body site tested using the TG device ......................................................................................29

4.5 Spatial configurations of the Peltier elements ........................................................................32

4.6 Static and Dynamic testing procedure ....................................................................................33

5.1 Thermal thresholds on the forearm ..........................................................................................36

5.2 Graphs of the continuous unpleasantness rating in response to the five thermal stimuli

applied in (a) dynamic and (b) static mode ...........................................................................38

5.3 Percentage of ‗Burning‘ descriptors used between uniform and TG configurations ...............39

5.4 Box plots indicating VAS ratings between different configurations ......................................40

5.5 Progression of the perceived thermal quality of the TGS ........................................................43

5.5 Scatter plot of CPT vs. maximum VAS score of the TGS.......................................................44

A.1 Screenshots of User Interface ................................................................................................62

B.1 Participant feedback form ......................................................................................................63


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List of Tables

2.1 Comparative chart showing previous thermal grill devices used in research ..........................13

4.1 Accuracy of ramp rates ............................................................................................................24

4.2 Order of presentation of stimuli ...............................................................................................34

5.1 Descriptors chosen to describe the three thermal grill stimuli .................................................41


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Glossary

List of Abbreviations

CDT Cold Detection Threshold

CNP Central Neuropathic Pain

CNS Central Nervous System

CPT Cold Pain Threshold

HPC Heat Pinch Cold cells

HPT Heat Pain Threshold

NRS Numerical Rating Scale

PT Pain Threshold

SCI Spinal Cord Injury

SD Standard Deviation

TG Thermal Grill

TGI Thermal Grill Illusion

TGS Thermal Grill Stimulus

VAS Visual Analog Scale

WDT Warm Detection Threshold


x

List of Parameters

k thermal conductivity ( Watt/(mK) )

F variance of the group means / mean of the within group variances

p probability of obtaining a test statistic at least as extreme as the one that was

observed

2

discrepancy between the expected and observed number of times each outcome

occurs

http://en.wikipedia.org/wiki/Probability

http://en.wikipedia.org/wiki/Test_statistic


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Chapter 1

Introduction

“…despite the severity of chronic pain, often you have almost nothing to show for it

physically. And that makes treating pain really subjective.”

- Melanie Thernstrom ―The Pain Chronicles‖, August 2010

1.1 Motivation

The capacity to experience pain has a protective role. By contrast persistent pain

syndromes, as is often seen in spinal cord injury (SCI) patients offers no biological

advantage and often produces drastic impairments in the daily routine and quality of life

of these individuals [1]. This pain is frequently more debilitating than major motor

impairments, such as the inability to stand, walk, sit and grasp. It often leads to

depression, which in severe cases results in suicide [2].

The chronic pain syndromes develop within months following the SCI. As the pain

occurs due to the injury to the central nervous system this type of pain is referred to as

central neuropathic pain (CNP). On average, close to 30% of individuals with SCI

develop CNP following the injury. Typical clinical manifestations of CNP are sensory

loss and spontaneous pain such as burning, spontaneous and stimulus-evoked pain [3].

The functional impact of CNP following SCI is profound and is demonstrated by a study

which reported that 37% of the individuals with SCI who suffer from CNP would trade

pain relief for any chance of regaining motor function [4].


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Currently, there is no treatment to prevent the development of neuropathic pain, nor to

adequately, predictably and specifically control established neuropathic pain. The aim of

treatment, thus far, is often just to help the patient cope by means of psychological or

occupational therapy, rather than eliminate the pain. Medications include opioids,

anticonvulsants, and adjuvants targeted at the CNS. However, the success of these

treatments is greatly limited by side effects, such as dizziness, sedation, coordination

problems, and dose dependence. Furthermore, opioids commonly result in only a 20-30%

reduction in pain intensity [5].

The development and validation of diagnostic clinical tools in the form of questionnaires

has undoubtedly been one of the most active and productive aspects of clinical research

on CNP in the last decade. However, these questionnaires fail to identify about 10 – 20%

of patients with clinically diagnosed neuropathic pain [6]. More importantly, these tools

provide little information about the causal lesion or disease and offer no framework for

the clinical management of pain and the assessment of the effects of various treatment

options [7, 8].

Etiology alone or the distribution and nature of the pain symptoms provide minimal

information on the mechanisms responsible for CNP [9]. Animal studies have identified a

number of nervous system abnormalities that produce symptoms similar to CNP in

humans. Unfortunately, it is difficult to translate the findings from animal studies into

simple tests that can be used in humans to identify the specific mechanism(s) that

produce each individual's CNP [10]. Hence, progress in management of CNP is

contingent on targeting underlying mechanism(s) of CNP in each individual, i.e.,

―mechanism-based‖ diagnosis and treatment.


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1.2 Hypothesised cause of CNP

Research into the mechanism of neuropathic pain showed a distinct loss of thermal

sensibility in regions of neuropathic pain but failed to explain the reason behind this.

Craig [11] using non-invasive methods of psychophysical analysis, proposed that the

thermal sensation in regions of central neuropathic pain (CNP) may reflect similar central

nervous system (CNS) interaction between warm and cold sensory inputs that underlie

Thermal Grill Illusion (TGI). The TGI is a perception of burning pain in response to a

thermal stimulus in which innocuous cool (20°C) and innocuous warm (40°C) stimuli are

presented simultaneously, in an interlaced pattern. Craig hypothesized that the burning

pain felt by central pain patients is caused by the loss of cool inputs, which consequently

releases (or disinhibits) integrated polymodal nociceptive activity in the lamina I

pathways [12]. He further used evidence from neuro-imaging and animal studies to

support this ―thermosensory disinhibition‖ hypothesis. Additionally, it was shown that

the mechanisms underlying the TGI were pharmacologically distinguishable from those

underlying noxious thermal pain [13]. Based on the validity of his hypothesis, Craig

proposed the use of the Thermal Grill (TG) as an investigative tool to study the

mechanisms of central neuropathic pain and theorized that any agent that could be used to

block the TGI can in turn be used for alleviating neuropathic pain and that the absence of

the TGI would act as a diagnostic for CNP [14].

However, hitherto there is no standardized TG device or testing protocol to study CNP.

Thus, the purpose of this thesis is to aid in the development of a standardized TG and to

investigate the effects of different spatial and temporal configurations of the TG on the

perception of the TGI.

1.3 Roadmap of the Thesis

This document consists of seven chapters. Chapter 1 provides an overview of the

motivation and hypothesis behind the study. Chapter 2 contains relevant background


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information for the study: aetiology of central neuropathic pain and the thermal grill

illusions as well as prior art. Chapter 3 describes the main objective of this research

study. Chapter 4 provides a detailed description of the study‘s methodology. It details the

apparatus design, involved design decisions, subjects and experimental design. Chapter 5

summarizes the experimental results and Chapter 6 discusses these results. Finally,

Chapter 7 concludes this study while highlighting the key findings.


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Chapter 2

Background

2.1 Central Neuropathic Pain

According to the International Association for the Study of Pain, central neuropathic pain

(CNP) is defined as ―pain caused by a lesion or disease of the central somatosensory

nervous system‖ [15]. This includes all pain due to any lesion along the neuraxis

including: the dorsal horn, the ascending pathways throughout the spinal cord and brain

stem, the thalamus, the subcortical white matter, and the cerebral cortex.

The CNP symptoms can be divided into two broad categories based upon their

dependency on peripheral stimuli: 1) spontaneous pain - which occurs independently of

peripheral stimuli, may be persistent, and may be described as numbing, burning, cutting,

piercing or electric-like pain [16] and; 2) peripherally evoked pain - which occurs in

response to either normally non-noxious or noxious stimuli. Hyperalgesia, a stimulus-

dependent (evoked) pain, is an exaggerated response to a painful stimulus; allodynia, is

defined as pain evoked by a stimulus that is normally not considered painful [16]. An

example of hyperalgesia is when a small pinprick results in a sharp, stabbing pain. An

example of allodynia is when something as innocuous as the light touch of clothing is

painful and unbearable.

Identifying and diagnosing the specifics of someone's neuropathic pain requires a

thorough examination, including a history, physical and neurological evaluations [17]. A

history allows the physician to begin to pinpoint which parts of the body are affected

and what parts of the nervous system may be involved. In a neurological exam, the

investigator observes the response to various types of stimuli such as: light touch, cold,


6

heat, pressure and pin pricks. The response to stimulation of various body locations is

mapped out to determine the nature of the neurological deficits.

Currently neuropathic pain is treated mainly with medications. Anticonvulsants (seizure

medicines), antidepressants and anti-arrhythmics are categories of drugs commonly used

to combat neuropathic pain [18]. A completely different class of drugs, namely opioids

(or narcotics), are sometimes prescribed for CNP. Because of side effects as well as

perceived possible addiction issues, their use is still somewhat controversial. Patients

also often go through an intensive psychotherapy program to address issues of

despondency, depression and despair that may arise secondary to the long-lasting impact

of CNP [18].

2.2 Central Neuropathic Pain and Spinal Cord Injury

Among various medical diagnostic groups, the greatest prevalence of CNP is in those

with SCI [5]. Siddall et. al.[3] classified the types of pain seen after SCI. Within the

neuropathic group he classified the clinical presentation into three categories based on

location of the symptoms as follows; 1) above-level pain, which occurs at regions cranial

to the injury site; 2) at-level pain, which occurs in regions near the SCI, where pain is

often characterized as stabbing or is stimulus-independent; and 3) below-level pain,

which is localized to regions distal to the injury site and is often classified as a stimulus

independent, continuous burning pain [5]. CNP is either at-level or below-level

neuropathic pain. Classification of these pains can be further refined according to the

structure or pathology.

Historically, CNP has been classified only descriptively by the above mentioned

symptoms and CNS injury site/pathology, without a clear understanding of the specific

mechanisms underlying each person's pain [19]. However, animal studies have revealed

that multiple molecular and cellular nervous system mechanisms underlie each pain

symptom and many different mechanisms can produce the same pain symptom. A


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criticism of animal models however, is the lack of a direct measure of pain; the tests

available are based solely on the observation of behavioural changes and adverse

reactions to a given stimulus [20]. Thus, animal studies alone cannot establish the precise

relationship between painful symptoms and mechanisms, and in this respect human

studies are needed. In order to validate and test these hypotheses and bridge the gap

between our knowledge of neurophysiological mechanisms and the clinical diagnosis and

treatment of neuropathic pain, researchers are looking to better understand the

somatosensory phenotype of patients [22].

Various authors have recently proposed that the careful analysis of the psychophysical

measures of somatosensory function in individuals with CNP can help identify subgroups

of patients based on somatosensory patterns and correlate the specific individual patterns

with the likely underlying mechanisms of CNP [21, 22, 23].

2.3 Psychophysical Testing

The first step towards mechanism-based treatment is hence, to characterize the

somatosensory profile of patients as precisely as possible. Psychophysical methods

specifically quantitative sensory testing (QST), non-invasively evaluate somatosensory

function.

QST measures the relationship between the characteristics of a physical stimulus

(modality, location, intensity and timing) and an individual‘s perception of that stimulus

[24]. QST was developed to overcome some of the limitations of qualitative traditional

bedside examinations, by allowing a more precise assessment of the magnitude of

sensory deficits and a quantification of thermal allodynia and hyperalgesia [65]. QST

systems are separable into devices that generate specific physical stimuli and those that

deliver electrical impulses at specific frequencies [25]. Devices that generate highly

controllable, ramping thermal stimuli utilize the ‗Peltier principle‘, in which the intensity

and direction of current flow controls the surface temperature of a test electrode

(thermode). The thermode contacts the skin and a subject is asked to report the sensation


8

of temperature change or heat/cold pain. A technical challenge for QST is to deliver a

sensory stimulus and determine accurate and reproducible sensory thresholds in a

reasonable amount of time [24]. Tests for pain sensation have the additional challenge of

minimizing the number and duration of stimuli that are unpleasant to the patient.

Rolke et al. (2006) established a standardized protocol and age- and gender-matched

absolute and relative QST reference values from healthy subjects, across different body

parts. Recently, Backonja et al. (2009) using thermal QST tools, proposed a new

standardized protocol for the psychophysical testing of patients with NP. This protocol,

although an important first step towards the individualized characterization of

somatosensory profiles, is limited to the testing of sensory thresholds to a single type of

stimulus (for example warm, cold, or touch). Threshold testing of patients with SCI

revealed that CNP was only present in areas with impaired or absent heat pain sensibility

[26, 27], and was confined to areas of maximal thermal deficit [28]. Although Rolke‘s

protocol identified that the loss of thermosensation was a significant correlate of CNP, it

did not adequately characterize the relationship between the observed thermosensory

deficits and CNP.

Craig [14] used the Thermal Grill Illusion (TGI) as a psychophysical method to

understand the interaction between innocuous cold and warm cutaneous sensory inputs.

The TGI is an illusion of heat pain, that is often burning in nature, when a person‘s skin is

in contact with interlaced innocuous cool (20°C) and innocuous warm (40°C) stimuli

[29]. Craig proposed that the loss of thermal sensation in regions of CNP may reflect

similar CNS interaction between warm and cold sensory inputs that underlie the TGI..

The following section shall provide an in depth look at the hypothesized mechanism of

the TGI.


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2.4 Thermal Grill Illusion

As described by Defrin [26], several hypotheses have been developed in an attempt to

explain the neural mechanisms that define different pain qualities. An early theory,

namely the ―pattern theory of pain‖, states that pain is signalled via non-specific channels

concerned with the conduction of both nociceptive and non-nociceptive events, and is

dependent on the degree of excitation of these channels [30, 31]. However, the

identification of specific receptor organs for detecting noxious stimuli in 1968 [32], led

scientists to discard this theory. A contradictory view, which was introduced by Muller,

and is better known as the ―labelled-line code‖, maintains that pain is processed via

dedicated pathways and that the excitation of a specific sensory receptor elicits the same

amount of pain regardless of the stimulus energy [33]. However, this view was

contradicted by the observation that neither damage nor stimulation of somatosensory

cortices affects pain, and that clinical stimulation of somatosensory thalamus can

alleviate chronic pain. A third view, proposed by Wall and McMahon (1986), states that

the perception of pain is due to the central integration of sensory information, including

information derived from the response of nociceptors. Work carried out by Defrin et al.

(2002), further supported this latter theory by showing that the quality of thermal pain is

determined by integration of information conveyed simultaneously by both dedicated

pain pathways and a non-nociceptive thermal pathway. In this perspective, an imbalance

or lesion in the thermosensory systems may contribute to CNP after SCI. Craig further

proposed that pain could be considered a ‗homeostatic emotion‘ and an aspect of

interoception or the physiological condition of the body [35].

The ascending neural activity that represents all physiological conditions of the body is

conveyed by the lamina-I spinothalamocortical pathway. Lamina-I, the most superficial

layer of the spinal dorsal horn, is the only neural region that receives monosynaptic input

from small-diameter (Aδ and C) primary afferent fibres [35], which innervate essentially

all tissues of the body. The Aδ- and C-type primary afferent fibers that are relayed by

lamina-I, transmit homeostatic information — specifically ‗pain and temperature‘

sensations — from all tissues.


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There are two classes of neurons that signal sharp pain and burning pain, that selectively

receive inputs from Aδ-nociceptors and polymodal C-nociceptors (HPC), respectively. In

addition, there are two types of thermoreceptive lamina-I cell that respond selectively to

cooling or warming [36, 37].

Research indicates that the summated activation of lamina 1 HPC cells (noxious heat,

pinch and cold) causes a conscious perception of pain in humans and signal burning pain

at low temperatures (<15 ºC). The lamina-I (COOL) cells that are sensitive to cooling

respond predominantly to Aδ-fibre input and have ongoing discharge at normal skin

temperature that is inhibited by warming. They display a linearly increasing response at

temperatures below a neutral skin temperature (~34ºC) and reach a plateau at cold

temperatures in the noxious range (<15 ºC) [38].

Craig (2002) proposed that the illusion of thermal grill-induced burning pain, could be

explained by the relative activity between the spinothalamic thermal and nociceptive

channels (refer to Figure 2.1). The burning sensation caused by polymodal C-nociceptor

activation of HPC cells, is normally masked centrally by the cold sensitive Aδ-fibre

activation of COOL cells. When the activity of cooling receptors is reduced due to the

presence of interlaced warm stimuli in receptive field (as is the case in the TG stimulus),

the HPC activity that is evoked by cooling is disinhibited centrally and causes a burning

sensation at these temperatures that is normally felt only at noxious cold temperatures

[39]. The effect of the thermal grill stimulus is a relative balance of HPC and COOL cell

activity that is similar to the relative activation seen in response to a noxious cold

stimulus of ~10ºC; the equivalence of which has been verified psychophysically [12, 40].


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Figure 2.1 Mechanism of the Thermal Grill Illusion. The burning pain sensation caused by

polymodal C-nociceptors (HPC), which are sensitive to noxious heat as well as to noxious cold, is

normally masked centrally by the activity of A -fibre thermoreceptors that are responsible for

cooling. When the activity of cooling receptors is reduced due to the presence of interlaced warm

stimuli, the HPC is disinhibited centrally and causes a burning sensation or the TGI (Figure

adapted from [14]).

2.5 TGI and Central Neuropathic Pain

Craig and Bushnell (1994) were the first to investigate the TGI in the context of the study

of pain, particularly CNP [14]. Craig speculated that the unmasking mechanism

underlying the TGI mirrors the patho-physiology of some neuropathic pain patients. A

majority of patients suffering from neuropathic pain due to SCI have dysfunctional

thermal sensibilities in which a dramatic loss of warm/cool temperature sensation is seen

in regions of ongoing pain [12]. Craig observed that this characteristic closely mimicked

the TGI, in which reduced warm/cool sensations are reported.

Based on electro-physiological recordings of spinal dorsal horn neurons in animals and

neuro-imaging (fMRI) studies in humans, Craig proposed the "thermosensory

disinhibition" hypothesis to explain the TGI and the burning pain. Namely, Craig


12

suggested that: 1) the paradoxical burning induced by the TG was due to the reduction of

the inhibition normally exerted by cold afferents on the nociceptive pathways in the

central nervous system; 2) in certain individuals, CNP may similarly reflect imbalanced

integration of pain and temperature; and 3) the TGI can be used to evaluate the

presence/absence of the central nervous system mechanism for cold-inhibition of pain.

A preliminary study of subjects with CNP, as a consequence of multiple sclerosis, further

supported Craig‘s hypothesis [41]. The patient in this study reported less pain in response

to the TGS than to the cool component (20 °C) itself. Furthermore, a study carried out on

a patient with complex regional pain syndrome-I (CRPS I) reported that the patient

experienced an intolerable burning sensation on her affected hand when it was placed on

the TG [42]. A study carried out by Kern et al. (2008) provided evidence that the central

mechanism underlying the TGI is pharmacologically distinguishable from the neural

mechanisms underlying both innocuous thermal sensations and noxious thermal

sensations. Kern found that the administration of morphine (known to suppress the

activity of lamina-I nociceptive neurons) produced correlated reductions in the pain

intensity reported in response to the TGS. If the hypothesis that the fundamental

dysfunction in CNP is the same mechanism that underlies the TGI holds true, then

any agent that blocks the TGI could be efficacious for alleviating CNP, and the

absence of the TGI effect would be diagnostic for CNP .

Craig further proposed the use of the TG as an investigative tool to examine the

mechanisms of pain. The TG has potential for further studying and understanding the

interactions between the thermal and nociceptive pathways. In particular, the TGI

imitates symptoms of CNP in healthy volunteers. Kern et al. (2008) similarly discussed

the potential of using the TG as a tool to uncover the physiological mechanisms and

impacts of analgesics on CNP.

Despite its potential value for studying pain mechanisms in humans, there are only few

studies that evaluated the psychophysical properties of the TGI or its application as an

investigative tool for patients with CNP [12, 43, 44, 45]. Furthermore, based on the above

evidence, it can be concluded that a standardised TG device is needed to advance


13

research in this area. The lack of research on the TGI may be attributed to the fact that

there is no commercially available or standardized TG device or standardized research

methodology [14].

2.6 Research Problem

2.6.1 Thermal Grill Devices

Existing TGs were created purely on an ad hoc basis for research purposes on healthy

subjects and vary in terms of design, size of thermal actuators, rates of temperature

change, range of temperatures and materials that couples skin and the thermal actuator, as

depicted in Table 2.1 [19, 43, 44, 45, 46, 47]. The existing diversity makes it difficult to

compare data obtained from different researchers and can negatively affect the results and

conclusions drawn from the studies.

Researcher Number of

Actuators

Actuator size Surface

Material

Sensation

produced

Manufacturer

Green [43] 4 x 4 0.64 cm2

Copper plate Non-painful heat

at mild temp

Pierce Laboratory

Bouhassira

[45]

1 x 6 (bars) 1.2 x 16 cm

(3 per bar)

Copper plate Painful sensation Seicer (France)

Defrin [26] 1 x 6 (pair

of)

3 x 3 cm Aluminum

plate

Painful sensation TSA 2001 –

Medoc

Fruhstorfer

[46]

1 x 6 35 x 8 x 0.8mm Bronze plate Non-painful heat In-house design

Leung [44] 1 x 10 0.75 x 10 cm Copper tubes Painful sensation In-house design

Alston [47] 2 cylinders 7.5 x 12 cm

0.5 mm (diam)

Brass

cylinders

Non-painful heat In-house design

Craig [19] 1 x 15

(bars)

20 x 14 cm Silver plate Painful sensation In-house design

Table 2.1 Comparative chart showing some of the previous thermal grill devices used in research.

A high degree of variation is seen in both the grill layout and actuator size.


14

2.6.2 Research Methodology

Leung et al. (2005) tested various combinations of innocuous temperatures (18/42°C,

20/40°C, 22/38°C, 24/36°C) in order to evaluate the potential of using the TG as a

research tool. They found that the subjects reported the most painful sensation for the

20/40°C and 18/42°C combinations. Bouhassira et al. (2005) showed that the frequency

and intensity of the painful sensation produced by the TG was directly related to the

magnitude of the difference in temperatures between the warm and cool bars. The

combination of increasingly colder temperature to a given warm temperature was shown

to induce similar effects as combining increasingly warmer temperature to a given cold

temperature. These results suggested that pain can be the result of a simple addition of

non-noxious warm and cold signals. Studies conducted by Li et al. (2009) using a 6x1

array TG, demonstrated that the occurrence of the TGI did not display a significant

dependence on gender. Research conducted by Dranga et al. (2008) in our laboratory,

investigated the effect of stimulus duration on the perception of the TGI. Dranga found

that at the 5 sec time point, the continuous pain ratings in response to the TGS were

significantly higher than those in response to the warm and cool stimuli alone [49]. Also,

at the 60 sec mark, the pain reported in response to the TGS was significantly higher than

that reported in response to the uniform stimuli.

To date, research on the TGI with relation to CNP has shown little consistency in terms

of methodology. Prior psychophysical testing of the TGI was limited to the distal upper

extremity, i.e., the palm and/or forearm. However, CNP can occur in any area of the

body, thus necessitating that the TG be adaptable for applications to any surface of the

body [21].

Li et al. (2009) using a thermal stimulation apparatus composed of six hollow brass bars

perfused with warm or cold water, tested twenty-one different stimuli applied to a group

of 19 healthy subjects on the glabrous skin of the palm and fingers. By using various

combinations of warm and cold bars and by alternating the number of bars in contact

with the skin, they showed that neither the distance between adjacent warm (40±1° C)


15

and cold (20±1° C) bars, nor the number of the stimulation bars (2 – 6) notably affected

the occurrence of the TGI.

Previous studies have also shown a huge variation in the method of application of the TG

stimulus. The original animal studies conducted by Craig (1994) used a dynamic

protocol; the temperature of the grill was varied to a set-point temperature while the

participant made contact with the grill. However, subsequent studies in humans have each

used different skin contact times and methods of application of TG such as: a) 3sec

(dynamic – The subject places his/her hand on the TG, at which point the grill was held at

an adaptation temperature for a period of 5min before being warmed/cooled at a rate of

±2.0º/s to a target temperature. After the target temperatures were reached in all

actuators, the desired temperatures were held for 3sec. The subject‘s skin was in

continuous contact with the thermal actuators) [43], b) 10sec (static – The subject‘s skin

contacted the actuators after they had been heated or cooled to the target temperature.

The fingers remained in contact with the grill for the entire duration of the 10sec long

experiment) [44] and c) 30 sec (static - The subject‘s skin contacted the actuators after

they had been heated or cooled to the target temperature, and stayed in contact with the

grill for the entire duration of the 30sec) [45]. Green and Pope (2003) reported that the

TGI is optimally perceived when thermal ramping and stimulation occur as the actuators

rest against the skin for the entire stimulation period (dynamic condition), i.e. no

simultaneous tactile contact, and TGI is infact greatly reduced by simultaneous cutaneous

tactile inputs i.e. contact suppression occurring when the subject places their hand on the

grill simultaneously as they first experience the TG stimulus (static condition).

Additionally, both Leung and Bouhassira (2005) noted that while using static testing

conditions, the quality and intensity of the sensation could change during the TG stimulus

and infact decreased with time.

As the TGI illusion can be simply produced by the simultaneous application of warm and

cool stimuli, a number of different patterns of these warm and cool stimuli can be

imagined, that can invoke the TGI. Figure 2.2 demonstrates this fact with the case of the

3x2 array TG used in this thesis.


16

Figure 2.2 Thermal Grill stimulation patterns. Six possible temperature configurations that

can be produced using a 3x2 TG array.

No research has been carried out to date, that examined the effect of different temperature

patterns on the TGI. Preliminary research carried out in our laboratory has shown that the

spatial distribution of warm and cool stimuli can significantly affect the perceived

intensity of the TGI [50].


17

Chapter 3

Research Objective

3.1 Objective

The goal of this thesis was to design the user interface and data acquisition system of a

prototype thermal grill device and to use it to further describe the TGI amongst healthy

subjects, while investigating the physiological factors which underlie this phenomenon.

In light of this goal, the following paragraphs outline the research objectives.

An important feature of the TG device was the ability to control the individual stimulus

elements and hence produce various thermal stimulus patterns. An aim of this thesis was

to explore this feature and help determine the best thermal element pattern and spacing

that could be used to elicit the TGI.

To evaluate the ramping functionality of the TG, a pilot study was designed to study the

effect of static vs. dynamic grill testing (i.e. w/o and w/ ramping) on the TGI.

This thesis also aimed to compare an individual‘s thermal thresholds using one vs. six

thermal actuators and hence investigate the relation between thermal thresholds and

stimulation area. A further objective was to design a pilot study to explore the relation

between the measured thermal thresholds and a subject‘s TG intensity ratings, using the

same stimulation area.

An objective of this thesis was to minimize any subject bias towards reporting the TGI as

painful, hence the study had to be designed such that subjects were, at no point instructed

that the sensation they would experience would be ‗painful‘. Rather subjects were simply

told to expect a unique sensation to the TG configurations and to rate the level of


18

unpleasantness. This is in contrast with prior research [11, 12, 27, 43, 62] that asked

subjects to specifically report and rate their sensations of pain.

3.2 Hypotheses

This thesis investigated the following three research hypotheses:

(1) The Thermal Grill (TG) device can be used to generate a painful sensation in

healthy individuals. This hypothesis originates from the prior findings that the

simultaneous application of warm and cool stimuli can produce a burning

sensation, known as the TGI [39, 43, 44, 48].

(2) The Thermal Grill Illusion (TGI) can be evoked in each able-bodied

individual. This hypothesis is based on Craig‘s thermosensory disinhibition

theory [12] that states the central mechanism underlying the TGI is the same

as that underlying CNP and hence the TGI should be present in all able-

bodied individuals. According to that theory, the absence of the TGI would

hence act as a disgnostic for CNP.

(3) The intensity of the TGI is dependent on the distribution pattern of the warm

and cool actuators in the TG stimulus. This hypothesis is based on preliminary

research carried out demonstrating that the spatial distribution of warm and

cool stimuli can significantly affect the perceived intensity of the TGI [50].


19

Chapter 4

Methodology

This section will begin with a detailed overview of the Rehabilitation Engineering

Laboratory TG prototype, followed by a description of the experimentation protocol to be

used in order to meet each of the project objectives.

4.1 Thermal Grill Apparatus

To address the need for a standardized thermal grill, a custom designed prototype was

created by an external contractor (Oven Industries; Mechanicsburg, Philadelphia) in

affiliation with the Rehabilitation Engineering Laboratory (REL), to further study the

effects of the TGI. Oven Industries was primarily in charge of the mechanical design and

construction of the device, as well as the preliminary design of the control system for the

grill.

The major contributions made in the thesis towards the design of the TG device are

highlighted below:

(1) Creation of the requirements for the hardware design of the TG and the

subsequent testing of the device prototype to ensure that requirements were

met.

(2) Design of the user interface to facilitate easy use for users with little to no

technical background.

(3) Partial design of the control system to ensure reliable temperature control,

data acquisition, and recording of the subject‘s response.


20

4.1.1 Hardware Design

Requirements: The grill must contain a minimum of 6 individual square contact-

thermodes arranged in a 3x2 matrix to allow for testing of different temperature

patterns/configurations. Each element must be individually controlled to allow for a range

of stimuli between 0 to 50°C and must be capable of achieving a ramp rate of at least

1°C/s. Contact thermodes which will be in touch with the skin, should be composed of a

material that allows for maximal heat transfer and should not exceed 60mm x 60mm. The

spacing between the thermodes should be such so as to allow for no temperature leakage.

Each thermal element must be monitored by a thermistor for continuous temperature

feedback of the thermode-skin interface (resolution 0.6°C).

Methodology: Research shows that thermal detection thresholds and thermal pain

thresholds vary inversely with the amplitude and the duration of the stimulus, hence

making it important to maintain a constant thermode size in any comparative studies of

thermal thresholds [36]. Additionally, the ramp rate achievable by the peltier element is

dependent on the power rating and therefore the size of the element. Hence, a trade off

had to be made between the size and achievable ramp rates in order to meet the desired

specifications.

Recent studies conducted by Pavlakovic et al. also revealed that the choice of the material

that couples the skin and the thermal actuator, and hence the heat transfer capacity of the

coupling material, can highly influence a person‘s thermal sensory detection and thermal

pain detection thresholds [51]. Materials with high thermal conductivities (such as

aluminum: kAl = 250, copper: kCu = 401, and silver: kAg = 429) tend to transfer heat/cold

throughout their surface more evenly and more rapidly [52]. Table 2.1 displays the

coupling materials used for TG devices to date.

Auditory noise produced by the thermal stimulation device has also been shown to

significantly raise the heat pain and cold pain thresholds of the subject [53]. Hence, a

water circulating cooling unit, as opposed to a fan cooled unit, was chosen for the device

to minimize auditory noise.


21

Implementation: The TG device consists of a matrix of six thermal actuators or

thermoelectric modules (TEM), each measuring 50mm x 50mm (Figure 4.1). The

direction of current flow between the two surfaces of the TEM dictates its action as a heat

generator or a heat sink. Each TEM is individually capped by an aluminum tile

measuring 50.8mm x 50.8mm x 5mm.

Figure 4.1 Isometric 3-D view of the Thermal Grill Device used in this study (a) top view and

(b) bottom view

The thermal tiles are arranged in a 3x2 grid, thermally isolated from each other with an

inter-tile gap of 1.02mm, allowing for a 61cm2 flat testing platform (Figure 4.2). The tiles

are placed atop of a water-circulating heat sink to ensure rapid temperature shifts, thus

allowing an operating surface temperature between 0 to 50°C.

Figure 4.2 Mechanical drawing of the Thermal Grill device developed by Oven Industries in

collaboration with REL.A1, A2, B1, B2, C1 and C2 represent the array tiles.


22

Each array tile is individually monitored by a class ―T‖, 15 kΩ thermistor (TS-67, Oven

Industries, USA) embedded in the aluminum cap, 1.9cm below the surface of the grill, for

continuous temperature feedback of the tile-skin interface (resolution ±0.5°C). This

temperature measurement is then used by a closed-loop proportional-derivative-integral

(PID) controller to regulate tile temperature in real-time [54]. The tiles have dedicated

controllers enabling the experimenter to define a programmable temperature profile for

ramping or a steady-state temperature for each tile individually.

The box housing the array tiles has connectors allowing for easy connect/disconnect from

the cooling unit and control modules.

Evaluation: The device was evaluated in terms of its: a) accuracy of thermistor readings;

b) disturbance rejection to touch, i.e., heat perturbation; and c) accuracy of ramp rates.

To assess the accuracy of the thermistor readings, the individual tiles were set to a range

of temperatures from 0 - 50°C and the thermistor readings of the individual tiles were

compared to those obtained using an external thermocouple monitoring device (Omega

HH21A monitor with Thermocouple MQSS series exposed probe - 0.25mm diameter,

Omega Technologies, Stanford, USA). The temperature was measured on the surface of

the tile both at the centre of the tile and on the perimeter. The accuracy of the TG‘s

thermistor readings at both locations (tile centre and perimeter) were found to be within

the range of ±0.2°C; well within the specified limits.

The disturbance rejection of the system is a measure of how well the system overcomes

perturbation caused by skin contact with the thermal tiles. A tile temperature of 0°C

would ensure the maximum temperature differential between the tile surface and the

user‘s skin (32-36°C), and is thus used to measure the worst case disturbance rejection

behaviour of the system. Figure 4.3 demonstrates that at a set-point temperature of 0°C,

contact of the subject‘s forearm with the tile surface causes a 0.4°C spike in temperature

for a period of 10 sec before returning to steady state temperature. This falls well within


23

the requirements for the TG to control temperature within ±1° C (i.e., (40±1° C) and

(20±1° C)).

Figure 4.3 Disturbance rejection of the device at 0°C. At a set-point temperature of 0C, tactile

contact with the tile surface causes a 0.4C spike in temperature for a period of 10 sec. Red arrow

indicates the time when the contact with the tile occured.

The accuracy of ramp rate was verified by measuring the time taken by the tiles to reach

and stabilise at the set temperature using a given ramp rate. The device was found to

function well under ramp rates of 0.5 to 4°C/s. At higher ramp rates (approximately 5 -

15°C/s), an overshoot in reaching the desired temperature was seen as the PID controller

had to increase the current flow to the peltiers. For the purpose of this thesis, only ramp

rates of 0.5 and 1.0°C/s were used. Table 4.1 demonstrates the measured accuracy of

these ramp rates.


24

Start Temp

(C)

End Temp (°C)

Temp diff (°C)

Ramp Rate (°C/s)

Time to reach set point w/o forearm (s)

Time to reach set point w/ forearm (s)

20 32 12 1 12.2 12.4

32 20 -12 1 12.3 12.3

32 40 8 1 7.9 8.0

40 32 -8 1 7.8 8.3

40 20 -20 1 20.0 20.5

20 40 20 1 20.4 20.7

20 32 12 0.5 23.6 24.0

32 20 -12 0.5 24.3 24.5

32 40 8 0.5 15.9 15.9

40 32 -8 0.5 16.3 16.2

40 20 -20 0.5 39.4 40.0

20 40 20 0.5 40.5 40.3

Table 4.1 Accuracy of ramp rates. Time taken to reach set temperature using a given ramp rate

measured using an external stop watch. All readings are averaged values, obtained from three

trials done (w/o) with no physical contact with the grill; and (w) with hand placed on the grill

4.1.2 Software Design

Requirements: The user interface had to be designed for clinicians and researchers with

minimal technical background, and must allow for reliable temperature control, data

acquisition, and recording of the subject‘s response.

The primary response measure was a computerized Visual Analog Scale (VAS) [55]

rating of unpleasantness. The representation of the VAS was a graphic that consisted of a

slider on a horizontal line with the anchors labelled by work descriptors (see section 4.3.2

below).The subject used a mouse to move an onscreen indicator along the line to the

point that they felt represents their current perceived stimulus-induced unpleasantness

level. Software was developed to record and display the VAS response as a function of

time. Any left-right movement of the mouse was translated into a corresponding value on

the VAS. The software controller automatically recorded data input by the test subject as

well as the tile temperatures sampled at every 0.1 seconds and stored it in an excel file.


25

Additionally checks were required to be placed within the software to ensure the safety of

the subject being tested and to prevent any overshoot in temperature beyond threshold

limits.

A further requirement of the interface design was that the subject should have no prior

knowledge of the grill configuration that he/she is being tested with, in order to remove

any form of bias from the feedback.

Methodology: The user interface was designed by taking the following facets of user

interaction into account [56]:

Functionality Design – The functionality as far as relevant to the user, including

actions and objects required by the system to accomplish the goals of the project and

satisfy the potential needs of the users.

Dialog Design – Structure of the interface without any reference to presentational

aspects i.e. the navigational structure and dynamic behaviour of the interface. Dialog

design aspects such as suitability of design for the specified task, self-descriptiveness,

conformity with user expectations, etc.

Presentation Design – The actual representation of the user interface including details

such as layout, colors, sizes, and typefaces.

To increase usability, the functionality and hence design requirements of the system

needed to be well defined in order to support the TG experiment methodology tasks in

the most optimal manner. Checks had to be put in, to ensure patient safety where

appropriate. Besides defining the major components of the user interface in terms of

functionality, the dynamics of the user interface (i.e. user interaction with the system)

needed to be specified as well. For example, clicking on the screen to indicate a pain

threshold had to stop the temperature ramping of the thermode and bring the thermode

back to adaptation temperature.

The design had to take into consideration all aspects of the user‘s interaction with the

system including the amount of mental strain that the design has on the user. Pre-set


26

configurations and choices pertaining to the task at hand were included in the interface to

reduce the amount of mental load on the user [56].

Implementation: The user interface and data acquisition system of the device were

designed using LabView software (National Instruments ™, v 9.0 (2009), Texas, USA).

The display was split so that the subject was only allowed to see his VAS rating while the

research coordinator had display of the temperature control, data acquisition, real time

temperature and the subject‘s feedback. Additionally the grill configurations were tested

in a randomised order. This ensured that the user had no prior knowledge of the grill

configuration being chosen by the research coordinator for testing.

The user interface was divided into three modes of testing: Static, Dynamic and

Threshold Testing, that mimicked the modes of testing commonly used by clinicians and

researchers for TGI studies.

The Method of Limits methodology [57] was used for sensory threshold testing. The

temperature of the TG tiles was simultaneously increased/decreased at a constant,

researcher defined, ramp rate. The subject was instructed to terminate the ramp by

clicking down at any point of the screen, at the moment the requested sensation was

perceived. This simple push-button response by the subject was also recorded by the

computer and completed each cycle of the examination.

For TG testing, i.e. static and dynamic grill modes, pre-set grill configurations were

delivered, upon the researcher‘s choice. Both the ramp rate and the trial duration were

also defined by the researcher. There were two modes of application, termed ―static‖ and

―dynamic‖. For the current study ―static mode‖ was defined as follows: the thermal

actuators were set to a predetermined temperature configuration before stimulus

application. While the actuator was in contact with the subject, temperatures remained

constant. In contrast, the ―dynamic mode‖ was defined as follows: the thermal actuators

set to the reference adaptation temperature (30°C), and then applied to the subject.

Temperature change from adaption temperature to target temperature was initiated after


27

contact with the skin. Temperatures then remained constant after the target temperature

was achieved.

A LED indicator was turned on to indicate when the subject should place his/her forearm

on the TG when testing in the dynamic or threshold testing mode.

The TG thermodes could be selectively powered on/off thus providing the option to use

the grill in different configurations, for example as a 2 x 3 array or a 2 x 2 array.

A computerised VAS scale displayed on the subject‘s screen, allowed for real-time

capture of the subject‘s response to the TG stimulus. The subject‘s response was also

simultaneously displayed on the researcher coordinator‘s screen. Time stamped data was

automatically stored in a user defined excel file every 0.1 seconds. The user interface

(UI) was programmed to have the VAS scale automatically zeroed at the start of the

experiment. This helped eliminate the initial spike in VAS recording that may arise if the

mouse was not properly zeroed (i.e., far left of the screen).

Continuous graphical and numerical feedback of the thermodes temperatures was

displayed to the research coordinator in real time to allow proper monitoring of the

device (refer to Appendix A).

An adaptation temperature of 30°C was pre-programmed into the grill. Before each trial,

the grill automatically defaulted to this adaptation temperature for a period of 10 sec, thus

ensuring that the subject‘s skin was kept at the same temperature before each thermal

stimulus.

Evaluation: The device was evaluated in terms of: a) the time lag between user response

and data acquisition; and b) the response time to subject feedback.

The lag in the data acquisition system was defined as the delay from the point at which

the user clicks the mouse to the capturing of data (tile temperature values) by the data

acquisition system. Since the mouse used was a USB connected device, this lag was the

summation of the Windows USB polling lag (8ms) and the Data Acquisition system


28

sampling rate (100msec) [58]. This lag could be considered negligible for the purpose of

this study as it was significantly below the average user response time (2.0 ± 0.5 sec)

[48].

To ensure that the grill temperature did not exceed the subject‘s pain threshold during

testing, the response time of the software to subject’s feedback during thermal testing was

monitored by an external timer. This was measured as the time between the subject

clicking down on the mouse to indicate a threshold and the instant temperature ramping

stopped and the tiles returned to adaptation temperature. This interval was calculated to

be ±0.1 s and the maximal temperature increase/decrease after the threshold indication,

was measured to be 0.2°C. Please refer to Appendix C, Thermal Grill User Manual, for a

detailed overview of the device operation and user interface.

4.2 Subjects

Eighteen participants were recruited through advertisements posted throughout the St.

George campus of the University of Toronto. Candidates were screened by telephone to

assess eligibility. Individuals were included if they were male, between 20-40 years of

age, generally healthy, and fluent English-speakers. Participants were asked to refrain

from consuming caffeinated products for 3 hours before testing. Exclusion criteria

included individuals suffering from or having previously suffered from any of the

following diseases or symptoms:

Systemic or neurological disease

Psychiatric disorders

History of diabetes or any other disease that can affect the peripheral nerve

function

History of chronic pain

Any skin disease, hypersensitivity or contact allergies

Experiencing any pain prior to the experiment.


29

4.3 Experimental Procedure

To maintain consistency between subjects and between multiple experimental runs,

testing was performed in a quiet room with the temperature maintained at 23 ± 1°C.

Further, to limit inter-subject variability in data, only the forearm of the non-dominant

side of the subject was used for testing, as demonstrated in Figure 4.4. Dominance was

determined by the Edinburgh Laterality Quotient score [67] a measurement scale used to

assess the dominance of a person's right or left hand in everyday activities. The choice of

non-dominant side for testing was dictated by the fact that this allowed the subjects to use

their dominant hand to indicate their response to testing. The participants were instructed

to place their anterior forearm in contact with the TG.

Figure 4.4 Body site tested using the TG device. The non-dominant anterior forearm, was used

for testing.

During all experiments, the participant was asked to apply only enough pressure to ensure

full contact with the TG tiles. Before each stimulus, the tile was set back to the adaptation

temperature (30°C).

Participation entailed a single testing session, which lasted approximately two hours with

twenty 30sec test conditions as follows: a warm stimulus (all tiles set to 40°C - Figure

4.5.a); a cool stimulus (all tiles set to 20°C –Figure 4.5.b); and the thermal grill

configurations (patterns of tiles set to interlaced temperatures of 40 and 20°C– Figures

4.5.c, 4.5.d and 4.5.e). The order of presentation of the test conditions was randomly

assigned based on a computer generated sequence.


30

The duration of stimulation was chosen based on pilot experiments conducted by

Bouhassira et al. (2005) which indicated that for forearm stimulation a duration of upto

20 – 30 seconds (depending on the combinations of temperatures), was necessary for

stabilization of the sensation.

The choice of temperatures was based on the results from past studies, which indicated

that the combination of 20 and 40°C effectively elicited a painful TGI amongst most of

the participants [12, 44, 45, 59]. Additionally, these temperatures are outside the range of

nociceptor activation and were thus appropriate for TG testing.

4.3.1 Pre-Testing

Prior to the experiment, each participant was asked to read, understand, and sign a

consent form. Participants were informed that the purpose of the study was ―to evaluate

the range of responses to the TGI amongst a group of healthy individuals‖. Participants

were not informed about the quality of the sensation that they would experience ensuring

no pre-disposition to reporting a painful sensation. The research coordinator then

explained the procedure of the experiment and the different testing conditions that would

be used. Please refer to Appendix D for the detailed study script.

4.3.2 Participant Feedback

A computer-driven visual analog scale (VAS) (see section 4.1.2) was used to

continuously sample the participant‘s current perceived unpleasantness of the TG thermal

stimulus. Participants were requested to move a linear, mouse-driven scale, displayed on

the monitor, to register their unpleasantness rating; with the leftmost point being

described as ‗not unpleasant‘ (VAS value of 0) and the rightmost point described as

‗most unpleasant‘ (VAS value of 10). To ensure the validity of the VAS across


31

individuals, subjects were asked to relate the anchor points to ‗the least unpleasant

sensation imaginable‘ and ‗the most unpleasant imaginable‘.

During stimulus application, the participants were asked to verbally report on the primary

sensation felt at 10sec and 30 sec intervals (Figure 4.6) from the instant that the stimulus

was initiated.

At the end of a trial for each test condition, participants were asked to pick a word(s) out

of a list of descriptors (refer to Appendix B) that best described the overall sensation

evoked by the grill.

4.3.3 Determination of Thermal Thresholds

4.3.3.1 Uniform thermal stimulus

Thermal threshold testing was conducted on the subject‘s forearm in the following order:

cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold

(CPT), and heat pain threshold (HPT). The method of limits protocol described by

Yarnitsky et al (1995) was used to determine thermal thresholds.

Two sizes of stimulus applications were used; one tile, or all six tiles. In this procedure,

the temperature of one or all six TG tiles were first maintained at adaptation temperature

(30°C) and were then decreased/increased at a rate of 1°C/s for cold and heat pain

thresholds (CPT and HPT) respectively, and by 0.5°C/s for cold and warm detection

threshold (CDT and WDT). The participant was asked to signal the reach of a threshold

by clicking on a computer mouse, at which point the temperature on the tiles stopped

ramping, reversed the direction of temperature change, and returned to the pre-configured

adaptation temperature.

Three trials were run to measure each of the thresholds, with a minimum inter-trial

interval of 30sec between the determination of detection thresholds and 60sec between

the determination of pain thresholds (PTs).


32

4.3.3.1 Thermal grill stimulus

The threshold testing protocol when all six tiles were active in grill mode (i.e. interlaced

warm and cool configurations) required the participant to click on three separate buttons

on the screen to indicate their CDT, WDT and PTs. Three consecutive trials were run for

each of the three grill stimulus configurations. The results from the consecutive runs for

each configuration were averaged together to determine the thresholds for that

configuration.

4.3.4 Evaluation of optimal grill configurations

In order to identify the optimal stimulation pattern of the TG, individual tiles were set to

warm or cool temperatures in various patterns.

Figure 4.5 Spatial configurations of the peltier elements to be tested. Red indicates the peltier

is set to a warm temperature and Blue indicates that the peltier is set to a cool temp.

In static grill condition, the TG was set to one of the five configurations in Figure 4.5 in a

randomised order. Once the tile temperatures had reached steady state, the participant

was asked to place his forearm on the TG for 30sec. The configurations included both

thermal grill patterns as well as uniform stimuli. Based on prior research conducted in the

laboratory [48], three TG patterns, as illustrated in Figures 4.5(c), 4.5(d) and 4.5(e), were


33

chosen to be tested in order to determine the best thermal element pattern that can be used

to elicit the TGI.

Each of the above thermal configurations was run twice. During the first run, the

participant was asked to provide his verbal feedback on the thermal grill sensation.

During the second run, the participant was asked to use the online VAS to continuously

rate the intensity of unpleasantness he was experiencing in response to the stimulus. This

breakup of the experimentation methodology in two separate runs allowed the participant

to devote his complete attention to the continuous VAS rating by eliminating the

simultaneous need for verbal descriptors. At the end of each VAS run, the participant was

asked to pick his overall sensation from a list of descriptors. Figure 4.6 represents the

order of presentation of stimuli during static and dynamic testing trials.

Figure 4.6 Static and Dynamic testing procedure. Each TG configuration was tested twice. In

the first run the subject responded using a questionnaire and the online VAS. In the second run,

the subject verbally described his sensation at the 10 and 30sec mark.

4.3.5 Evaluation of dynamic thermal grill

In the dynamic grill condition, the participant was asked to place his forearm on the grill

and the grill was maintained at an adaptation temperature of 30°C for a duration of 60sec,


34

after which the tiles began ramping (1C/sec) until they reached the set-point

temperature. This temperature was held for a duration of 30sec with the participant‘s

forearm being in contact with the grill throughout the process. The thermal configurations

chosen for thermal testing were the same as shown in Figure 4.5, and were administered

in a randomised order.

There were two runs for each thermal configuration. During the first run, the participants

used the online VAS to dynamically rate the level of unpleasantness felt during the 30sec

testing period (Figure 4.6). In the second run, participants were asked to provide verbal

descriptors of the primary sensation of the stimulus.

4.3.6 Order of Presentation

Table 4.2 depicts the order of execution of the study. The order in which the five thermal

grill patterns were tested was randomized. A minimum 1 minute rest period was given

between each TG stimulus for static and dynamic testing.

Table 4.2 Order of presentation of stimuli. Patterns 1,2,3,4,5 represent the grill configurations

shown in Figure 4.5 that were used for testing. The order of the configurations will be randomly

assigned based on a computer generated randomised sequence.

Threshold

Testing

(Single

Tile)

Threshold

Testing

(Six Tiles)

Static Grill

Testing

Dynamic Grill

Testing

C

D

T

W

D

T

C

P

T

H

P

T

PT + DT VAS Descrip. VAS Descrip.

Pattern 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5


35

Chapter 5

Results

5.1 Subjects

Eighteen young men (mean age of participants was 25 years (SD = 2)) participated in the

study. The majority of participants were right-handed (n = 16).

5.2 Thermal Thresholds – Spatial Characteristics

The CDT, WDT, CPT and HPT were measured on the forearm on the subjects with one

thermode and with all six thermodes, to study the spatial properties of temperature

thresholds. The temperature of the tiles was ramped up/down from a baseline temperature

of 30C until the subject indicated a threshold was reached. Both pain thresholds and

detection thresholds measured with a single thermode were significantly higher than

those measured with six adjacent thermodes (One-way ANOVA; p ≤ 0.05, in all four

cases i.e. CPT (p = 0.05), CDT (p < 0.001), HPT (p = 0.011) and WDT (p < 0.001). The

decrease in thresholds with the increase in stimulation area indicates the presence of

spatial summation of thermal stimuli. Figure 5.1 presents the group pain thresholds and

detection thresholds measured with both one and all six thermodes.


36

Figure 5.1 Thermal thresholds of the forearm. Box-plots of the Cold Detection threshold

(CDT), Cold Pain threshold (CPT), Warm Detection threshold (WDT), and Heat Pain threshold

(HPT) are depicted for both one (_1) and six (_6) tiles. The bottom, middle, and top lines of the

box represent the 25th, 50

th, and 75

th percentile value, respectively. The whiskers represent the

minimum and maximum values.

5.3 Pain Elicited by the TG

The thermal grill Pain Threshold was measured in subjects as the temperature differential

of the thermodes in each of the TG configurations (starting from a baseline temperature)

that induced the sensation of pain (using a ramp rate of 1C/s). Only 4 subjects (22.2%)

reported pain thresholds to the TGS before the TG boundary temperatures i.e. 20C for

the cool stimuli and 40C for the warm stimuli, were reached. The average temperature

differential of the TGS required to elicit pain in these four subjects was found to be

11.94C (SD = 1.05).

In 5 out of the remaining 16 subjects who did not indicate pain to the 20/40 TGS, the

thermal grill Pain Threshold was measured by allowing the temperature of the tiles to

exceed the 20C and 40C boundary temperatures. In this case tiles were ramped from a

baseline temperature upto a cool stimulus temperature of 0C and a warm stimulus

TEM

PER

ATU

RE


37

temperature of 50C, or until a subject indicated their pain threshold had been reached.

The average temperature differential of the TGS required to elicit pain in the five subjects

was found to be 29.26C (SD = 3.98).

The inter-configuration difference in thermal grill pain thresholds as measured above was

not found to be significant. The thermal grill pain thresholds were further examined in

relation to the subject‘s thermal pain thresholds (i.e. the HPT and CPT). A significant

correlation (Spearman‘s correlation: = 1.00, p < 0.001) was found between the subjects

thermal grill pain thresholds (averaged between the three thermal configurations tested

for each subject) and the differential between their thermal pain thresholds (HPT – CPT)

i.e. subjects with a low HPT and low CPT were found to have a lower threshold to the

TG stimulus, and vice versa.

5.4 Static vs. Dynamic thermal testing Intensity Ratings

The maximum pain intensity ratings recorded using the visual analog scale were analysed

by performing a Paired t-test (within-subject factor: stimulus type). The effect of static

TG condition was found to be significant when measured at the 5sec mark (Figure 5.2).

The maximum reported pain ratings were significantly higher in the dynamic testing

condition than in the static testing condition at the time point (Config_1: F= 17.0, p =

.003, Config_2: F = 17.0, p = .001, Config_3: F = 17.0, p = .005, Config_4: F = 17.0, p<

.001, Config_5: F = 17.0, p = .031). However, at 30sec, the difference between the

unpleasantness ratings for static and dynamic grill condition were not found to be

significant (p > 0.05). Figure 5.2 compares average pain intensity ratings recorded using

the VAS under conditions of static versus dynamic grill contact. The time variation of the

VAS ratings was also examined in relation to the TG configurations.


38

Figure 5.2 Graphs of the continuous unpleasantness ratings in response to the five thermal

stimuli applied in (a) dynamic and (b) static mode. Using an on-line VAS (0-10), a rating was

obtained every 100ms.The line graphs depict the continuous rating of pain over 30 s, averaged

across the 18 participants. By the 5s mark, the unpleasantness intensity ratings in response to the

dynamic stimulus were significantly higher than the static condition in all five configurations (p<

0.05). At 30 s, the difference between the unpleasantness ratings for static and dynamic grill

condition were not found to be significant (p> 0.05).

The frequency of ―painful‖ or ―burning‖ reports for the dynamic TGS was significantly

more than those for the static stimuli (p < 0.001). Additionally, when comparing the static

and dynamic testing conditions, the percentage of participants reporting nociceptive

sensations to the grill configurations was found to decrease to a greater extent for the

uniform thermal configurations than the TG configurations (p < 0.05), as shown in Figure

5.3.

5.5 Grill Configurations and TG intensity rating

Of the 18 subjects, 15 reported pain and/or unpleasantness (when asked to orally describe

the sensation) in response to the TGS (83.3%). Subjects were significantly more likely to

report pain in response to the thermal grill configurations than the uniform warm and cool

stimuli (Wilcoxon test; Z = -2.828, p = 0.005 for warm vs. TGS and Z = -2.00, p = 0.046

for cool vs. TGS) as demonstrated in Figure 5.3. However, no statistically significant

difference was seen in the average or maximum unpleasantness intensity VAS ratings


39

reported by subjects between different grill configurations (One-way ANOVA; F =

0.380, p = 0.822 for dynamic condition and F = 0.909, p = 0.463 for static condition) and

between the TGS and uniform stimuli (warm vs. TGS; F = 1.576, p = 0.218 and cool vs.

TGS; F = 0.001, p = 0.980). Figure 5.4 graphs the average and maximum VAS scores for

each configuration in static and dynamic conditions.

Figure 5.3 Percentage of „burning‟ descriptors used between uniform and TG

configurations. Subjects were significantly more likely to report burning sensation or pain in

response to the thermal grill configurations than the uniform warm and cool stimuli in both static

and dynamic testing conditions.

STATIC

0

10

20

30

40

50

All Warm All Cool TGS

Percen

tag

e o

f p

arti

cip

an

ts

rep

orti

ng

th

e s

en

sati

on

as

'Bu

rn

ing

'

DYNAMIC

0

10

20

30

40

50

All Warm All Cool TGS

Percen

tag

e o

f p

arti

cip

an

ts

rep

orti

ng

th

e s

en

sati

on

as

'Bu

rn

ing

'


40

Figure 5.4 Box plots indicating VAS ratings between different configurations.No significant

difference was seen in (a) average VAS ratings and (b) maximum VAS ratings obtained across

subjects over 60s stimulus duration.

The time variation of the VAS ratings was also examined in relation to the TG

configurations. At the 5sec time point, the continuous unpleasantness ratings in response

to the TGS were significantly higher than those recorded at the thirty second time point

(Config_3: 2=18.669, p < 0.001; Config_4: 2=20.086, p < 0.001; Config_5:

2=26.525, p < 0.001).


41

5.6 Thermal Quality and Characteristics of the TGI

In 49.07% of the TG runs, subjects characterised the sensation as being ―burning‖ or

―painful‖ in nature. The use of these nociceptive descriptors (such as ‗burning‘ or

‗painful‘) were significantly more in the case of TGS than for uniform stimuli (Binomial

test: Z = 0.50, p = .002). Subjects who reported pain and/or unpleasantness to one or

more of the TGS were termed ―responders‖. Conversely, approximately 17% of this

study‘s sample reported feeling neither pain nor unpleasantness in response to the TGS (n

= 3) and were termed as ―non-responders‖ for the purposes of this study. Table 5.1 shows

the variation in response between responders and non-responders for various grill

configurations. This data is extracted from the questionnaires that subjects were required

to fill in after each 30sec VAS trial.

Table 5.1 Descriptors chosen to describe the three thermal grill stimuli. Descriptors were

chosen from a list provided to subjects as well the subject‘s own interpretation of the sensation.

The frequency reported in brackets indicates the percentage of participants that used a particular

descriptor. ―TGS responders‖ refers to participants that reported pain and/or unpleasantness in

response to the application of atleast one of the TGS. Participants were free to use as few or as

many words as they thought appropriate.

Condition All participants –

Descriptors (%)

TGS responders only –

Descriptors (%)

Static Warm (88.9) Neutral (11.1) Warm (93.3) Neutral (6.7)

Dynamic Warm (77.8) Burning (5.6) Warm(93.3) Burning (6.7)

Static Cold (77.8) Burning (10.1) Cold (73.3) Burning (13.3)

Dynamic Cold (66.7) Burning (22.2) Cold (100.0) Burning (20.0)

Static Mixed (40.0) Burning (11.1) Mixed (31.3) Burning (13.3)

Dynamic Mixed (35.0) Burning (27.9) Mixed (25.0) Burning (25.0)






42

When asked to identify the main underlying quality felt, subjects correctly identified the

thermal quality of the cool stimulus (config_2) in 78% of runs for static conditions and

67% of the runs for dynamic condition (describing it as ―cool‖ or ―cold‖). 90% of

participants correctly identified the thermal quality of the warm stimulus (config_1)in

static grill condition while 78% of participants described the stimulus correctly in

dynamic condition (describing it as ―warm‖ or ―hot‖).

60.2% of the TG runs were correctly identified as being mixed (i.e. warm and cool) in

nature. However, when subjects were asked to identify a single predominant thermal

quality, the TGS were more frequently described according to the warm component, i.e.,

as either ―warm‖ or ―hot‖ (count of ―warm‖ or ―hot‖ vs. ―cool‖ or ―cold‖: Binomial tests;

p = 0.02).

The use of painful descriptors for the different TG configurations was analysed.

Configurations involving a greater percentage of cool (i.e., cool columns surrounding a

warm column) was found to be significantly more painful and unpleasant than equal area

configurations having a larger region of warm stimuli (i.e. warm columns surrounding a

cool column) (χ2 = 3.846, p = 0.04). Figure 5.5 graphs the subject reported descriptors on

a thermal scale progressing from extremely cold to extremely hot sensations.


43

Figure 5.5 Progression of the perceived thermal quality of the TGS for (a) Static Condition

and (b) Dynamic Condition. Participants were asked to describe the predominant thermal

quality of the TGS at 10, and 30s. The temporal progression of the thermal quality of the

stimulus was coded as fixed combinations (e.g., when the participant initially indicated mixed

sensations that progressed to a predominantly hot sensation, this was coded as ―mix hot‖).

Combinations where the participants indicated pain and/or unpleasantness are located at the

extreme ends of the graphs. Cold sensations are located on the left-hand of the graph. This is

followed by combinations of cold and mixed sensations; mixed sensations; hot and mixed

sensations; finally, combinations indicating predominantly hot sensations are found on the right-

hand side of the graph.


44

5.7 Thermal Thresholds and the TGI

A Spearman‘s correlation was calculated for the four different thresholds and the

unpleasantness intensity ratings (NRS) elicited by the TG. The only threshold that was

consistently significantly correlated with these ratings was the CPT (ρ =0.550, p = 0.052

for static condition; and ρ =0.535, p = 0.049 for dynamic condition) as demonstrated in

Figure 5.6.

Figure 5.6 Scatter plot of CPT vs. maximum VAS score of the TGS. The CPT was found to be

significantly correlated to the TGS VAS score (averaged across the three TGS conditions) in both

static and dynamic grill conditions.

5.8 Variance in Response

Although the TGI was successfully elicited in a majority of subjects, the response to the

TGS between individuals was varied: pain intensity ratings ranged from zero (i.e., ―no

pain‖) to scores of ten out of 10 points (10 = ―worst pain imaginable‖). Subject reported

descriptors to the stimuli further reflect this variability. Non-responders perceived the

TGS to be ―warm‖ or ―hot‖. While a few non-responders described the TG stimulus to be

―neutral‖ and ―not unpleasant or pleasant‖, just two participants characterized the TGS as

―pleasant‖ and ―comforting‖. However, in the case of these two participants, only a single

configuration was characterised as being pleasant, while the other two TG configurations

were characterized as unpleasant. Responders described their experience with the TGS as

0

2

4

6

8

10

0 10 20 30

max

VA

S sc

ore

CPT (C)

STATIC

0

2

4

6

8

10

0 10 20 30

max

VA

S sc

ore

CPT (C)

DYNAMIC


45

―uncomfortable‖, ―unpleasant‖, ―painful‖ and a sensation they ―didn‘t like/disliked‖. One

responder reacted strongly to the TGS and could only maintain contact with the grill for a

maximum of 5 sec before withdrawing his hand.


46

Chapter 6

Discussion

The present results indicate that the simultaneous application of adjacent cutaneous warm

and cold stimuli, at stimulus temperatures below the heat and cold pain thresholds, is

capable of producing a paradoxical sensation with a burning quality in a large majority of

subjects (83.3% of subjects reported pain and/or unpleasantness to one/more of the TGS).

6.1 TGI as a Painful Experience

In this study, the burning sensation attributed to the TGS was coupled with reports of

pain and unpleasantness. The nature of the TGI has not been clearly defined and has been

a topic of debate [11, 39, 44, 45, 46]. Although a majority of the authors reported that the

TG sensation could be painful, its relationships with normal thermal sensitivities (under

the same spatial conditions) had not been specifically investigated. In this respect, the

present results (refer to Figure 5.3 and Table 5.1) clearly demonstrate, in a large number

of naïve subjects, that the paradoxical sensation induced by a thermal grill can be

described as painful and/or unpleasant and hence confirms the hypothesis that the TG

device can be used to elicit a painful sensation in healthy individuals.

This study investigated the characteristics of the TGI by employing warm (40 ± 1C) and

cold (20 ± 1C) stimuli of various configurations. Craig reported that the uniform 20°C

and 40°C stimuli were rarely rated as non-painful by their 11 participants [10]. None of

the 13 individuals that participated in Leung et al.‘s (2005) study commented on feeling

pain in response to the presentation of thermodes set to 18°C, 20°C, 24°C, 36°C, 40°C, or

42°C. In this study‘s protocol, participants were required to report on feelings of

unpleasantness in response to the thermal grill stimuli and were not given any indication


47

if the stimuli were to be painful or not. Compared to the warm and cool temperatures

alone, pain in response to the TGS was elicited more frequently and was often described

to be burning in nature as demonstrated in Figure 5.3.

6.2 TG perception during Static vs. Dynamic Grill testing

This study was the first to compare the effects of dynamic and static grill conditions of

the TGS within the same group of subjects. Results show that the paradoxical sensations

can be perceived during synchronized dynamic cooling/warming of the forearm to

innocuous temperatures, but this response was not apparent in the static testing

conditions. Thermal receptors are most active during a change of temperature [63, 64]. In

the case of static testing, a sudden temperature change is seen as the forearm is placed in

contact with the preconfigured TGS. In contrast, testing with the dynamic grill requires

that the forearm is resting on the grill (which is at skin temperature) before temperature

change begins. Intuitively one would expect to see a larger initial VAS response in the

static condition, since the temperature change is immediate and should cause the thermal

receptors to fire rapidly at the time of initial stimulation. However, the initial VAS

response was markedly higher in the static dynamic condition. Interestingly, this was

observed in response to both the uniform and the TG stimuli and was short lasting (given

the time frame). By the 30sec point there was no significant difference seen in the effect

of static vs. dynamic condition on the VAS ratings. This difference in the initial response

may thus reflect the effect placing the forearm on the thermode including; the effect of

tactile contact of the thermode with the skin surface, or factors related to the motor act of

placing the hand on the grill.

Tactile stimulation in the case of static grill testing activates the rapidly adapting

mechanoreceptors including Meissner corpuscle, Pacinian corpuscle, and hair follicle

receptors. Since they are rapidly adapting or phasic, the action potentials generated

quickly decrease and eventually cease. In the dynamic grill testing condition, tactile

receptors fire minimally due to adaptation to the stimulus [60]. Green (2009) reported


48

that temperature perception on the hand is attenuated and its quality is changed when

thermal stimulation is accompanied by simultaneous tactile stimulation. The

spatiotemporal properties of the tactile stimulus dictate the level of contact suppression,

and suppression did not occur in significant amounts when a thermode was lightly drawn

across the surface of the skin as opposed to being touched to its surface [61]. His results

strongly implied that contact suppression results primarily from stimulation of low-

threshold mechanoreceptors that are more sensitive to vertical impact than to skin

deformation and that touch contributes in fundamental ways to normal temperature

perception.

However, subjects voluntarily placed their forearm on the grill in the static condition

only. Voluntary movement could cause descending inhibitory inputs which could cause

suppression of nociceptive transmission in the dorsal horn or higher centres [38].

Additionally, placing the hand requires attention which may affect the initial perception

of the thermode, or ability to focus on movement of the mouse, and thus the ability to

respond accurately in the initial few seconds of stimulation. These possibilities were not

evaluated in this study, and require further study.

6.3 Spatial Characteristics of the Thermal Grill

Different temperature configurations of the TG were used in this study. Figure 5.2

demonstrates that no statistically significant difference was seen in the unpleasantness

VAS intensity ratings reported for each of the configurations during stimulus application.

However, in post-stimulation questioning, the TG configuration with a greater cool

stimulation area was described to be significantly more painful than configurations with a

larger warm stimulation area, as reported in Figure 5.3.

Throughout the experiment, participants were simply told to indicate the level of

unpleasantness of the TG stimulus. This protocol was designed to minimize any

suggestions that the grill may be painful and so were not asked to rate pain during the

stimulus application. Instead, participants were given a questionnaire with a list of


49

descriptors to choose from and were additionally asked to describe the sensation in their

own words. A TG stimulus may have been perceived as qualitatively unique to uniform

warm/cool stimulus but equally as unpleasant. This may account for the higher

percentage of ‗burning‘ or ‗painful‘ descriptors used for the TGS when subjects were

asked to describe the sensation in their own words, even though the VAS ratings for the

TGS and uniform stimuli were similar.

Overall, it can be shown that although there was no significant variance in the

unpleasantness ratings between the different TG configurations, a significant difference

was seen in the descriptors used for these configurations. Specifically, TGS

configurations with a larger cool stimulation area were described to be more painful. This

contradicts previous finding that show that a cool bar interposed in a field of warm was

much more effective at evoking the TGI [50]. In all, these results confirm the hypothesis

that the perceived intensity of the TGI is dependent on the distribution pattern of the

warm and cool bars in the thermal grill stimulus.

6.4 Temporal Characteristics of the Thermal Grill

Descriptor analysis showed that the perceptions varied with time in no observable

pattern. Similarly, Alston [48] reported that participants experienced a fluctuation

between detecting both warm and cool, and feeling ―heat‖.

Craig (2002) and Green (2009) also reported that the ability to detect the thermal quality

of ―cold‖ diminished during the simultaneous presentation of both warm and cool

temperatures (i.e., TGS). Leung et al (2005) comparing the perception elicited by the

TGS after 3sec of stimulation to that produced by a uniform stimulus, found that

participants matched the TGI to painfully hot stimuli that surpassed the temperature of

the warm component. He found that following 10sec of stimulation, the sensation evoked

by the TGS still resembled hot (and not cold) stimuli; however, the temperatures of these

stimuli were not significantly higher than the warm component of the TGS. These authors

suggested that the diminished noxious nature of the TGS may reflect adaptation of the


50

central process underlying the TGI. Bouhassira et al. (2005) reported that their

participants described mixed sensations in response to the TGS over the 30sec of

application. The current data supports the observation that the perceived thermal quality

of the TG evoked response fluctuates during stimulus application. Further study is needed

to evaluate whether this reflects participant‘s attending to aspects of the stimulus or the

effect of neuronal responses at lower levels of the nervous system.

6.5 TGI and thermal thresholds

The intensity of the painful response to the TGS was significantly correlated to the CPT

(Section 5.7). This finding suggests that the CPT and TGI share a common physiological

mechanism. Prior researchers hypothesized that cold thermoreceptive channels

(ascending lamina-I Cold) modulate the effect of nociceptive (lamina-I HPC) pathways

[12]. Both the CPT and TGI would be affected by this integration.

Preceding research has shown various lines of evidence suggesting a relationship

between cold pain, cold thermoreception, and the TGI. Following the administration of

morphine, there is a significant correlation between the reductions in the CPT and the

lower pain intensity felt in response to the TGS [43].Craig and Bushnell (1994) theorized

that the disinhibition of pain seen in the TGI was linked to the cold allodynia experienced

during myelinated nerve blocks. Additionally, in post SCI patients experiencing central

neuropathic pain, the painful areas were found to co-localize with areas of maximal

thermo-sensory deficits [27, 62]. Collectively, these results suggest a modulatory role for

innocuous thermo-receptive input in the perception of pain.


51

6.6 The between-subject variability of the TGI

Despite between-subjects variation in pain and detection thresholds, the thermal grill pain

threshold was found to be significantly correlated to the temperature differential between

the heat and cold thermal threshold (i.e. HPT - CPT).

The results from this study also indicate that the perception and intensity of the TGI is a

highly variable phenomenon between individuals. Three participants (representing 16.6%

of the sample) did not report either pain or unpleasantness from the TGS. Previous

researchers identified within their samples a similar proportion of non-responders [26, 27,

28, 43, 62]. This shows that the TGI can be evoked in a majority of able-bodied subjects

using the temperature combination of 20C and 40C, within the limitations of our study.

Of the four thermal thresholds, CPT is the most variable between subjects [22, 57].

Therefore, the relation between the subject‘s CPT and perception of the thermal grill

illusion may hold some insight into explaining the consistent proportion of non-

responders across the different studies. Further research needs to be carried out in order

to examine the role (played by) cold pain thresholds on the perception of the TGI.

6.7 Important methodological issues

A crucial methodological difference between the present experiment, and previous

research [11, 12, 27, 43, 62] lies in the instructions to participants.

In the present experiment the subjects were instructed to describe the evoked perception

for warm, cold, and simultaneous warm and cold stimulation by choosing descriptors

from a list (cold, cool, warm, hot, neutral, burning cold, other, burning heat), and

spontaneously describe the perception verbally. Additionally at no point in the pre- or

intra-experimental sessions, were subjects told that the sensation could be painful.

Subjects were simply told to expect a unique sensation to the TG configurations and to

rate the level of unpleasantness on a scale of 1 – 10. However, the participants still


52

volunteered comments indicative of the perception of ―pain‖ and ―stinging‖, which are

characteristic of the thermal grill illusion. In contrast, in the experiment by Craig and

Bushnell (1994) participants were given a list of 15 words from the McGill Pain

Questionnaire [66], and a common definition of pain as ‗any uncomfortable sensation,

such as pricking, stinging, or burning, even if the stimulus is tolerable‘. The replicability

of the painful grill illusion in subjects without prior bias shows that the perception of the

thermal grill illusion is a very robust phenomenon.

Whereas previous research measures thermal thresholds using a single thermode, this

study used the same stimulation area to measure both the thermal thresholds and thermal

grill intensity ratings [63, 65]. This allowed us to better understand the relation between

the thermal grill illusion and thermal thresholds.

Using the same component temperatures for the TGS across all individuals meant that,

for some trials, the cold temperature or the warm temperature fell either below or above

pain thresholds, respectively. To offset this possibility, some researchers have defined the

cool and warm temperature with respect to the CPT and HPT, respectively (e.g., CPT +2

°C/HPT -2 °C) [28, 43, 45, 61]. The use of fixed temperatures was based on prior

research [12, 44, 45] indicating that the 20 °C and 40 °C combination produced the TGI

in a high number of individuals.

6.8 Using the TG as a Research Tool

It was proposed that the TGS can be used to mimic the burning pain experienced by

neuropathic pain patients, as well as to evaluate the sensory effects of analgesic agents

[11, 45]. The device developed for this study allows for full control over stimulus

variables, i.e. thermode temperatures, spatial configuration of warm and cool thermodes,

number of thermodes used and temperature ramp rates. Additionally, the safety checks

are in place to ensure that the temperatures reached by the grill do not present a physical

harm to the participant, hence making it ideal for prolonged testing paradigms. Most


53

importantly, the grill is mobile and can hence be used for testing in any region of the

body where neuropathic pain may occur.

In this study, we were able to successfully elicit the TGI in a majority of the able-bodied

subjects. To use the TG effectively as a clinical research tool, further research must be

carried out to understand of the mechanisms that cause the TGI and hence reproduce it

consistently in a large sample of healthy individuals.

6.9 Limitations of this Study

In the present experiments, the thermal grill illusion was elicited through six thermodes

arranged in a 3 x 2 array with a total surface area of 61cm2. However, throughout the

history of research on the TGI various stimulation areas have been used to produce the

stimulations. The large actuator size used in this experiment may account for the

difference in pain ratings seen from prior research.

This study was not specifically designed to analyze the effect of tactile stimulation on the

TGI; but rather was designed to study the effect of the TG ramping functionality on the

TGI. Hence, the lack of control over the various variables involved in understanding the

difference between static and dynamic grill testing, presents a limitation in interpreting

the results.

The VAS is a well-studied method for measuring both acute and chronic pain, and its

usefulness has been validated by several investigators. Since pain is a very subjective

sensation, subjects often claimed it difficult to judge and mark their level on

unpleasantness on the linear length of the VAS scale. This may account for the

discrepancy seen between the verbal descriptors used by subjects and their corresponding

VAS ratings.


54

The room temperature, humidity level and ambient noise were controlled to the best of

our abilities. However, normal day to day variations do occur which have been shown to

have an impact on a person‘s perception of thermal stimuli [51, 53].


55

Chapter 7

Conclusion

There has been considerable interest in the use of the Thermal Grill Illusion (TGI) for the

study of central neuropathic pain. To this end, the present study developed a portable and

reliable device that could successfully elicit the TGI in a majority of the able bodied

subjects. The present study was also the first to compare the effects of dynamic and static

contact of the TG within the same group of subjects. Results show that static testing

conditions resulted in significantly suppressed initial responses to thermal stimulation.

The source of this difference requires further investigation. A high correlation was also

seen in the subject‘s TG intensity scores and their cold pain threshold. However, the

spatial arrangement of the warm and cool stimuli was shown to have a significant effect

on the quality perception of the stimulus but not on the intensity ratings of those same

stimuli.

Future studies should attempt to manipulate the TGS to further illicit the TGI in all

healthy subjects in an attempt to further elucidate the mechanisms of the paradoxical pain

response elicited by this mixed stimulus.


56

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Appendix A

Figure A.1. Screenshots of User Interface (a) Static Testing screen (b) Dynamic Testing screen

Waveform display

Set Dynamic Testing parameters

Temperature feedback

Temperature feedback

Preset Grill

Preset Patterns


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Appendix B

Figure B.1. Participant feedback form


64

Appendix C

THERMAL GRILL USER MANUAL

The Thermal Grill is a computerized device designed to enable the determination of a

psychophysical measure called the thermal grill illusion (TGI); an illusion of pain that

occurs in individuals when interlaced comfortable warm (40°C) and cool (20°C) bars are

applied to the skin.

1.1 Principle of operation:

The TG consists of 6 peltier elements, called Thermodes, arranged in a 3x2 matrix which

act as the contact surface with the subject‘s skin. The device is capable of heating or

cooling the skin, as needed.

An adaptation temperature of 30°C is pre-programmed into the grill to be used prior to

each thermal experiment.

For threshold measurement, a quantified measurable thermal stimulus is induced by the

device. A simple push-button response by the patient, recorded by the computer,

completes each cycle of the examination.

For thermal grill testing, preset grill configuration are included, which upon the user‘s

choice induce a thermal stimulus by the device. A mouse driven visual analog scale,

recorded by the computer, allows for patient feedback.


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1.1 Overview of Testing Methods

Threshold Testing

Detection of sensory thresholds depends on subjective data input. The Method of Limits

methodology is used by the device for sensory threshold testing. Testing consists of

stimuli of continuously changing intensity, which is halted by the subject at the moment

the requested sensation is perceived.

Static Testing

In Static Mode, the thermal tiles are set to a predetermined temperature configuration and

the thermodes will be held at that temperature till the experiment end.

Dynamic Testing

In Dynamic Mode, the tiles will be ramped up/down to a user defined temperature

configuration and be held at that temperature for the duration of the experiment at which

point the tiles will be ramped back to a reference adaptation temperature. Both the ramp

rate and the experiment duration are defined by the user.

1.2 Installation and Setup

1. Make sure that the TG controller modules are turned off.

2. Connect the ULinx Serial Connector to the USB port on the computer.

3. Check the water level within the cooling unit and ensure that no bubbles are

present within the tubing.

4. Plug the cooling unit into the power outlet and check to ensure that water is

circulating within the unit.

5. Connect the controller modules to a power outlet.


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6. Turn on all three of the controller modules (switch is located at the back of each

controller box)

1.3 Operation

The user interface is designed such that at all times, the experimenter and the subject

have different displays. This allows the experimenter to collect feedback data from the

subject without biasing the results. In the following pages, unless specified, the user

interface displays will refer to those seen by the experimenter. In majority of the test

cases, the subject is shown a blank screen alone.

The TG Main Screen that is illustrated below is displayed each time you enter the

Labview program.

1. Navigate to folder labeled ―Thermal Grill Code‖ located on the desktop and open

Grill-Final Version.vi to start the Labview program.

2. A Front Panel Labview screen displaying the TG User Interface pops up. To

access the back panel or System Block Diagram press Ctrl+e. This shortcut

allows you to easily switch between the front panel and block diagram screens.

3. Click on the arrow on the top right hand corner of the Labview menu (as indicated

below) to start Labview.

4. Click the Start Program button to activate the Thermal Grill program.


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5. The green light besides COMM PORT should light up to indicate that there is no

communication failure between the TG and the computer.

WARNING:

If the light is does not turn on, stop the program by clicking on the red stop sign in

the Labview menu (as indicated below). Unplug the USB series connector and

replug it. Repeat step 6. This would automatically restore the connection with the

Labview Program.

6. Peltier Status indicates which tiles are being actively controlled by the grill. To

deactivate a tile, press down on its corresponding switch on the screen.


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1.4 Running an Experiment

Static Testing Mode

Click on the Static Testing button on the main screen of the user interface to enter

this mode. The following screen will become visible to the experimenter.

Actual

Temperature

indicates the current temperature of each of the grill tiles as recorded

via the tile‘s embedded thermistor. Real time graphical feedback of

the tile temperature is also displayed on the screen

Set Temperature indicates the set point temperature of each tile as defined by the

experimenter.

Preset Patterns easy access grill set point patterns that the experimenter can define

by clicking down on their corresponding switches. The experimenter

is also given the option to enter in his own Customized Pattern for

the grill.


69

In static mode testing is done via two methods (a) Descriptive Response (b) Visual

Analog Scale

In Descriptive Response mode of feedback, the subject is asked to indicate their overall

sensation at the 10sec and 30sec. A stop watch has been built into the user interface

display for this purpose.

1. Select the Preset Pattern or a Customized Pattern for the grill by click down on

its corresponding switch. Once you do so the values of Set Temperature should

change to indicate your selection and the tiles will start ramping to reach this

defined temperature. The tile temperatures can be read numerically form the

Actual Temperature box or graphically on the screen display.

2. Once the tiles have reached their preset temperature configuration, ask the subject

to place his/her hand on the grill.

3. Click down on the Start button in the stop watch window to begin the counting.

The Elapsed Time indicates the number of seconds that have elapsed since the

stop watch was started. To stop the stopwatch, click down on the Start button

again.

4. To restart the stop watch simply click down on the Start button to reset and restart

the timer.

In Visual Analog Scale mode of feedback, the subject is requested to move a linear,

mouse-driven scale, displayed on the monitor, to register their unpleasantness rating. Any

left-right movement of the mouse is translated into a corresponding value on the VAS.


its corresponding switch. Once you do so the values of Set Temperature should

change to indicate your selection and the tiles will start ramping to reach this

defined temperature. The tile temperatures can be read numerically form the

Actual Temperature box or graphically on the screen display.

2. Click on the Patient Feedback – VAS button. The following screen will pop up

allowing the experimenter to specify the file name to which the subject feedback


70

data will be stored. Enter the necessary file name in the box labeled Patient

Feedback – Static and click on the button to enter testing mode.

3. The following screen will be seen by the experimenter which displays

numerically and graphically the current tile temperature as well as the

Pain/Unpleasantness rating as indicated by the subject.

4. The stop watch inbuilt on the screen allows the experimenter to time the

experiment duration.


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5. Simultaneously the following screen will be visible to the subject. The subject can

provide feedback by simply click on the screen to move the pointer along the

scale. All feedback will be automatically recorded and stored in the excel file

defined by the experimenter in Step 2.

6. At the end of the experiment duration, the experimenter must simple click on

Return to Static Testing to continue with the experimental protocol.


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Dynamic Testing

Click on the Dynamic Testing button on the interface main screen to enter this mode. The

following screen will appear on the experimenter‘s screen

Experiment

Duration

indicates the length of time that the tiles will be held at the

experimenter defined grill configuration before ramping back to the

adaptation temperature

Ramp Rates indicates the rate at which the tiles will ramp from the adaptation

temperature of 30°C to the experimenter defined set point

temperatures. All ramp rates are in °C/s.

Preset Patterns easy access grill set point patterns that the experimenter can define

by clicking down on their corresponding switches. The experimenter

is also given the option to enter in his own Customized Pattern for

the grill.

In dynamic mode, testing is done via two methods (a) Descriptive Response (b) Visual

Analog Scale


73

In Descriptive Response mode of feedback, the subject is asked to indicate their overall

sensation at the 10sec and 30sec. A stop watch has been built into the user interface

display for this purpose.


its corresponding switch. Select the Experiment Duration and Ramp Rates to

create a ramping profile for the grill.

2. Click the Testing button to begin the testing protocol. The following screen will

pop up allowing the experimenter to specify the file name to which the subject

feedback data will be stored. Enter the necessary file name in the box labeled

Patient Feedback – Dynamic and click on the button to enter testing mode.

3. The following screen will be seen by the experimenter which displays

numerically and graphically the current tile temperature. The stop watch inbuilt

on the screen allows the experimenter to time the experiment duration. The tiles

will follow the ramping profile as determined in step 1.

4. At the end of the experiment duration, the experimenter must simple click on

Return to Dynamic Testing to continue with the experimental protocol.


74

In Visual Analog Scale mode of feedback, the experimenter will follow the same steps as

described above. Although in this case the subject will provide feedback via the VAS

scale as done in Static Testing VAS mode.

Threshold Testing

Click on the Dynamic Testing button on the interface main screen to enter this mode. The

following screen will appear on the experimenter‘s screen.

In threshold mode, testing is done via two methods (a) Uniform Threshold Testing (b)

Thermal Grill Threshold Testing

In Uniform Threshold Testing mode, the tiles will be simultaneously ramped up/down to

the upper/lower temperature limit of the grill. A simple mouse click by the subject will to

indicate threshold limit, will stop ramping and the corresponding temperature will be

recorded by the computer.


its corresponding switch.

Select the Experiment Duration and Ramp Rates to create a ramping profile for

the grill.




Threshold Testing – Uniform and click on the button to enter testing mode.


75

3. Ask the user to click down on the screen when the threshold limit is reached to

stop ramping and return to the Dynamic Testing mode screen.

4. All feedback will be automatically recorded and stored in the excel file defined in

Step 2.

In Thermal Grill Threshold Testing mode, the tiles will be ramped up/down to an

experimenter defined TG configuration pattern. The subject is threshold feedback by

clicking on the appropriate buttons on the screen. Ramping stops once the subject clicks

to indicate that their pain threshold has been reached.


its corresponding switch. Select the Experiment Duration and Ramp Rates to

create a ramping profile for the grill.




Threshold Testing – Uniform and click on the button to enter testing mode.

3. The following screen will be visible to the subject to indicate their detection and

pain thresholds. All feedback will be automatically recorded and stored in the

excel file defined in Step 2.

4. When the subject‘s pain threshold limit is reached, ramping stops and the display

returns to the Dynamic Testing mode.


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Appendix D

STUDY SCRIPT

Before study:

- Ensure that TG are clean

- Turn on TG computer and software

- Ensure that the TG is working properly

- Set up and aim video camera on the grill

- Print out:

o Participant information/screening questionnaire

o Consent Form

o 2 Randomization Sheets

o 10 Qualitative Response

- Find out order for stimulus presentation

o Randomized grill configuration – static testing

o Randomized grill configuration – dynamic testing

During study:

Consent

Before we begin, I wanted to briefly go through the study. What we are interested in

recording is the perceptual response to the simultaneous application of pleasant

warm and cool stimuli across a body area. The body area being tested is the forearm.

Testing will be done using the thermal grill (point towards it). The temperatures across

the different elements will be set to one of three conditions: all warm, all cool, or a

mixture of warm and cool. The grill will be applied for a predetermined period of time.

You will be asked to describe the sensation this grill produces.


77

All data collected from you will remain confidential. This is done by using a number to

refer to your file. Any identifying information will be stored separately in a locked

cabinet. Also, only myself and my supervisors will have access to the information

obtained.

Your participation is completely voluntary, and you are free to withdraw from the study

at any point.

This consent form describes the information I just gave you. It also provides you with a

contact in case you have any questions regarding your rights as a research

participant. Please read through it thoroughly and, if you wish to participate, sign at

the bottom of the second page.

Sign form

Okay! Before we start, please go through this form and ensure that the information on it

is accurate (pass over Screening Questionnaire).

Just to make sure, you are not currently experiencing pain?

Okay, we are ready to begin the study.

TG Threshold Testing [Remember: ALWAYS test non-dominant side]

In the following tests, we will explore, using various procedures, how you perceive

temperature changes. In addition, we will examine, from what point on different test

stimuli are felt as being painful.

The test instructions will be read to you aloud. If you have not understood the test

instructions, please always feel free to immediately ask for clarification.


78

The grill is connected to this computer, so I can control the temperature to either warm or

cool your skin. Clicking on the mouse enables you to immediately stop the ongoing test

stimulus at any time.

For every test I will explain to you when to click down on the mouse.

So first of all, I will be conducting a trial run to familiarize you with the testing protocols.

CDT

Set ramp rate to 0.5°C/s

First we will test your ability to perceive cold sensations. Please click on the screen

immediately once you perceive a change in temperature to cool/cooler for the first time.

Once you click down please immediately remove your hand from the grill.

Subsequently, the tile will warm up again, until it reaches the baseline temperature. This

procedure will start in a few seconds.

WDT


Now we will test your ability to perceive warm sensations. Please click on the screen

immediately once you perceive a change in temperature to warm/warmer for the first

time. Once you click down please immediately remove your hand from the grill.

Subsequently, the tile will cool down again, until it reaches the baseline temperature. This


CPT



79

Now we will test as to when you perceive the cooling of the thermode as painful. Your

skin will be slowly cooled. At some point in time you will feel a second sensation on top

of the usual ―cold‖ sensation. The impression of ―cold‖ will change its quality towards an

additional impression of a ―burning‖, ―stinging‖, ―drilling‖ or ―aching‖ sensation.

Please click on the screen immediately once you perceive such a change. Please DO

NOT wait to click down on the mouse until the sensation has become unbearably

painful. Once you click down please immediately remove your hand from the grill.

Subsequently, the tile will warm up again, until it reaches the baseline temperature. This


HPT


Now we will test as to when you perceive the warming of the thermode as painful. Your

skin will be slowly warmed. At some point in time you will feel a second sensation on

top of the usual ―warm‖ or ―hot‖ sensation. The impression of ―warmth‖ or ―heat‖ will

change its quality towards an additional impression of a ―burning‖, ―stinging‖,

―drilling‖ or ―aching‖ sensation.

Please click on the screen immediately once you perceive such a change. Please DO

NOT wait to click down on the mouse until the sensation has become unbearably

painful. Once you click down please immediately remove your hand from the grill.

Subsequently, the tile will cool down again, until it reaches the baseline temperature. This


Testing within the control and test site

So now we will first do threshold testing with only one tile and then do the same for the

condition where all six tiles are changing temperature.


80

During the first condition, I want you to make sure that your forearm is in full contact

with the right-most tile in the lower row.

CDT - Set ramp rate to 0.5°C/s

Just as we have done in the practice round, you will first perceive a cooling of the skin.

Please click on the screen immediately as soon as you first feel a change of temperature

to ―cool or cooler‖. This procedure will be performed a total of 3 times.

WDT - Set ramp rate to 0.5°C/s

Please click on the screen immediately as soon as you first perceive a warming of the

skin. Again this procedure will be performed a total of 3 times.

CPT - Set ramp rate to 1.0°C/s

Please click on the screen immediately as soon as the ―cold‖ sensation changes its

quality to an additional sensation of ―burning‖, ―stinging‖, ―drilling‖ or ―aching‖. This

procedure will be performed a total of 3 times.

HPT - Set ramp rate to 1.0°C/s

Please click on the screen immediately as soon as the ―warm‖ or ―hot‖ sensation

changes its quality to an additional sensation of ―burning‖, ―stinging‖, ―drilling‖ or

―aching‖. This procedure will be performed a total of 3 times.

Now we will do threshold testing with all six tiles on. Please ensure that you forearm is

placed on the middle of the grill such that it makes contact with all six tiles.

CDT - Set ramp rate to 0.5°C/s

WDT - Set ramp rate to 0.5°C/s


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CPT - Set ramp rate to 1.0°C/s

HPT - Set ramp rate to 1.0°C/s

PT - Set ramp rate to 1.0°C/s

We are now going to test the device in thermal grill mode with a mixture of warm and

cool tiles in three different configurations. For each configuration I will ask you to

indicate your pain threshold and well as when you first detect either a cool or warm

sensation.

The screen will now have three buttons: ―cool‖, ―warm‖ and ―unpleasant‖.

Please click on the button labeled ―cool‖ immediately IF you detect a change of

temperature to ―cool or cooler‖.

Please click on the button labeled ―warm‖ immediately IF you detect a change of

temperature to ―warm or warmer‖.

Please note that you may feel both or only one of these sensations during the trial. Click

down only on the button you deem appropriate.

Please click on the button labelled ―unpleasant‖ immediately as soon as the sensation

changes its quality to an additional sensation of ―burning‖, ―stinging‖, ―drilling‖ or

―aching‖ pain. This procedure will be performed a total of 3 times for each

configuration.

Static Testing

Next we are testing a mixture of different scenarios: all warm, all cool, and three

configurations which have a mix of warm and cool tiles; first each of these conditions

will be administered in a static mode.


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For each of the testing conditions, I will set the grill to one of five configurations and will

then ask you to place your hand on the grill. Please do not make contact with the TG

until I tell you so.

Part 1

I want you to describe the primary sensation you feel after 10 and 30 seconds of placing

your forearm on the grill. I will give you a cue to indicate both these time points. Run

trial.

Part 2

As you can see, on the screen there is a scale ranging from “not unpleasant”, to “most

unpleasant”. The tick can be controlled using the mouse. The pointer should reflect the

level of unpleasantness you are feeling at the moment.

So, during certain trials, I will need you to place your hand on the grill for 30 seconds.

During this time, I want you to move the mouse along the scale indicating the degree of

unpleasantness you are feeling at that moment. This is meant to be interactive.

If the sensation increases during testing, you can move the mouse up the scale. If the

sensation decreases, you can move the mouse back down. Importantly, if you are not

feeling any unpleasantness, make sure the mouse is on the leftmost point of the scale.

Please focus on the stimulus during the trials.

Make sure to watch the screen to see what is being recorded.

Part 3

After these trials, I will ask you to complete a short, form to describe the overall

sensation felt from a list of six descriptors. If you think there is a better word that

describes your sensation, choose ‗Other‘, and write it out. Go ahead and read through the

selection.

Give them time to go through the list of descriptors. Run trial.


83

Dynamic Testing

Now we will run the same procedure as before but in dynamic mode. In this mode you

will keep you hand placed on the grill. Once you do so, the grill will be held at a neutral

temperature for 10 seconds and then be ramped up/down to one of five grill

configurations. I will indicate the 40 second mark at which point you will immediately

remove your hand from the grill.

Feedback will be down in the same manner as before.


Run trial.

Ask for feedback at 20 sec and 40 sec mark.

End

That‘s it! Thank you for participating. Do you have any questions, or comments?

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