Authors:Vera Lucia Moura, MDKeturah R. Faurot, PA, MPHSusan A. Gaylord, PhDJ. Douglas Mann, MDMorgan Sill, MPHChanee Lynch, BAMichael Y. Lee, MD, MHA
Affiliations:From the Department of PhysicalMedicine and Rehabilitation (VLM,KRF, SAG, MS, CL, MYL), andDepartment of Neurology, University ofNorth Carolina at Chapel Hill (JDM).
Correspondence:All correspondence and requests forreprints should be addressed to:Vera Moura, MD, Department ofPhysical Medicine and Rehabilitation,Program for Integrative Medicine,CB #7200, UNC Hospitals,Chapel Hill, NC 27599-7200.
Disclosures:Financial disclosure statements havebeen obtained, and no conflicts ofinterest have been reported by theauthors or by any individuals in controlof the content of this article.
0894-9115/12/9103-0000/0American Journal of PhysicalMedicine & RehabilitationCopyright * 2012 by LippincottWilliams & Wilkins
Currently, 1.6 million people in the UnitedStates live with a limb loss; by 2050, this numberwill likely double.1 Most persons undergo amputa-tion for peripheral vascular insufficiency, trauma,or malignancy, with greater numbers of lower thanupper limb loss (5:1 ratio).1,2 Individuals with limbamputation face physical and psychosocial chal-lenges during their adjustment process, including (1)impairment in physical functioning, (2) pain, (3)prosthesis use, (4) change in employment status, (5)alteration in body image and self-concept, and (6)poor psychosocial adjustment.3 Individuals with am-putation must often cope with chronic pain, includ-ing residual (stump) and phantom limb pain (PLP).
Current literature is divided on the impact ofPLP. PLP appears to be constant in only 18%Y25%of persons with amputation. In reported studies,the prevalence of PLP depends on how it is defined:Bany[ PLP ranges from 51% to 80%, whereas painexperienced at least a few times per week is reportedin 28%Y37% (Table 1).4,6,8Y11,13Y15 The incidenceand natural history of PLP is even more uncertain;only small, relatively brief longitudinal studies haveso far been reported.5,7,12,15 Longitudinal studiessuggest that PLP decreases in time,5,7,12,15 makinghigh prevalence estimates in populations several yearspost amputation even more notable and making theinterpretation of therapy efficacy very difficult. Painin other body locations as a result of prosthesis useis found in up to 45% of the population.16,17 PLP, achallenging source of chronic pain in this popula-tion, is the focus of this report.
Efficacious therapies to reduce the sufferingof persons with amputation are still elusive. Theliterature describes a variety of pharmaceutical, sur-gical, and other conventional therapeutic approachesto pain management in persons with amputation,includingmore than 30 types of therapy for PLP.18Y20
These procedures include the following modalities:(1) sympathectomy,21 (2) stump manipulation,21 (3)stump ultrasound,22 (4) injection with local anes-thetics and analgesics,21 (5) transcutaneous nervestimulation with discrimination training,23 (6) nerveblocks,24 (7) cordotomy,25 (8) pharmacologic ther-apies,20,26,27 and (9) myoelectric prosthesis.28 Theoverall findings of this literature conclude that thesevarious therapies range from ineffective to slightlyeffective. With conventional treatments for PLPhaving had mixed and often limited success,22,29
providers and the public have begun to examine anduse nonconventional approaches. However, clinicalstudies of nonconventional approaches reportingsome success in treating PLP are few in number, and
generally describe small numbers of subjects. Pub-lished studies on nonconventional or complementaryand alternative medicine approaches to treatmentof PLP have included acupuncture, energy healing,and mind-body therapies (e.g., hypnosis, biofeedback[including visual mirror feedback], eye movementdesensitization and reprocessing, guided imagery,and relaxation techniques).30Y33
Mind-body therapy approaches to pain man-agement are a small but growing area of investi-gation and use. The National Institutes of Healthstates that mind-body therapies focus on the in-teractions among the brain, mind, body, and be-havior, with the intent to use the mind to affectphysical functioning and promote health.34
Mind-body therapies use and enhance themind’s ability to be aware of and self-regulate symp-toms. Techniques include biofeedback, hypnosis,yoga, tai chi, qi gong, meditation, guided imagery,progressive relaxation, and deep breathing exercises.According to the 2007 National Health InterviewSurvey, 19.2% of adults reported using mind-bodytherapies in the past 12 mos.2,3
Research in mind-body medicine reveals thatthese therapies can enhance the ability to amelio-rate symptoms such as pain, stress, anxiety, depres-sion, and fatigue, often found in patients with chronicconditions, as well as improve coping ability andquality-of-life. For example, mindfulness meditationhas been shown to improve stress and mood35; yogawith controlled breathing and visualization has beenshown to decrease sleep disturbance,18 and hypno-sis has been found to reduce postsurgical pain anddistress.19,20
The prevalence of PLP among persons withamputation and its impact in terms of suffering andreduced quality-of-life, combined with the limita-tions of efficacy in conventional approaches, jus-tifies a continued search for alternative treatments.In particular, because mind-body therapies haveshown promise for self-regulation and ameliorationof various chronic painful conditions, an explora-tion of research on their application to PLPVa con-dition that exemplifies the complex interaction ofbody and mindVseems especially warranted. The pur-pose of this focused literature review was to evaluateexisting intervention studies of mind-body techniquesfor reducing PLP in persons with amputation.
METHODS
Data SourcesSystematic searches were conducted on PubMed
(MEDLINE), Institute of Scientific Information Web
2 Moura et al. Am. J. Phys. Med. Rehabil. & Vol. 91, No. 3, March 2012
of Knowledge, EMBASE, Cumulative Index to Nurs-ing and Allied Health, Cochrane libraries, and Alter-native Medicine Database electronic databases fromthe period of 1994 to 2010. Search terms includedthe following: amputee, amputation, psychologi-cal distress, phantom pain, depression, anxiety,stress management, mind-body medicine, medi-tation, guided imagery, imagery, hypnosis, bio-feedback, autogenic training, progressive musclerelaxation, yoga, breathing exercise, tai chi, andchi(qi) gong. A manual search of references fromretrieved articles was also conducted. Because ofthe paucity of intervention trials using mind-bodytechniques for amputation-related pain, both ran-domized-controlled clinical trials (RCTs) and studiesof lesser methodologic rigor were included, that is,simple clinical trials, case reports, and case series.Studies were excluded if they (1) lacked an inter-vention, (2) were not published in English, and (3)did not address PLP as the primary outcome amongpersons with limb amputation. Other than one dis-sertation, studies outside peer-reviewed journalswere not reviewed. Where overlapping reports werefound, only the most complete article was chosen.
Study SelectionOf 670 articles retrieved through search strat-
egies, 19 independent reports met the criteria andwere reviewed by two independent researchers. Ofthe 19 articles selected, 2 (including the dissertation)were randomized controlled clinical trials, 8 weresimple clinical trials, and 10 were case reports orseries. All studies addressed PLP. The studiesavailable for review reported results of interventionsin hypnosis, imagery, and biofeedback. No articlesthat met the review criteria were found for medi-tation, yoga, tai chi, or qigong as adjuvant therapiesfor pain and/or psychologic distress in amputees.
Data Extraction and Quality AssessmentInformation extracted from the studies in-
cluded descriptions of the following elements: (1)intervention technique, (2) sample size and com-position, (3) intervention duration, (4) follow-upperiod, and (5) detailed outcome assessments withstatistical analyses. The completeness of the de-scriptions of the above elements was used to judgethe quality of case reports and simple trials. RCTswere assessed with the quality criteria explicated byBalk et al.36
Non-RCTs and case studies are considered oflower methodologic quality because they do not ade-quately control for bias.37 Of the two RCTs reviewed,
TABLE
2Hypnosisforphantom
limbpainam
ongpersonswith
amputation
Case
Con
dition
Treatment
Results
P
Oakleyet
al.(20
02)30
case
review
PLPfor4yrs(AKA);
76-yr-oldwom
anEight
weekly25
-min
sessions
ofhypn
osis.
100%
pain
reliefa
ndcontinuedph
antom
sensations
n/a
Reviewof
11casesof
PLP
(duration,
0.5Y
25yrs)
(arm
,AKA,
BKA)
Hypno
sissessions
(3Y64)
ofvaryingleng
th.
Cases
includ
efive
ipsative-imageryY
andsixmovem
ent-im
ageryYbased
therapies.Five
includ
edrelaxation
training
;one,
cogn
itivetherapy;andon
e,mirrortherapy.
Reduction
inpain
frequencyor
intensity;
improvem
entin
physical
orpsycho
logicfunction
n/a
Bam
ford
(200
6)40;
uncontrolledtrial(n=25
)PL
P(m
eandu
ration
,7yrs)
(arm
,leg);10
wom
enand
15men
aged
27Y78yrs
Sixweeklysessions
+ho
mepractice
threetimes
daily
usinghypn
otic
analgesia,visualization
andmovem
entof
imaginarylim
b,psycho
logic
hypn
osis,and
self-hypn
osis
Sign
ificant
redu
ctionin
medianpain
after
intervention
,maintained6mos
later
(NRS,
8of
10to
3of
10);resultsno
tsensitive
toside
(right
vs.left)or
causeof
ampu
tation
(traum
avs.o
ther)(W
ilcoxon
)
G0.00
1
Rickard
(200
4)38
RCTn=20
PLPwith/witho
utstum
ppain
(arm
,AKA,
BKA;
0.5Y
63yrsago);
men
andwom
enaged
31Y70yrs
Threeindividu
alhypn
osissessions
vs.
waitlistedcontrol
Reduction
inpain
before
toafterintervention
.ByMPQ
-SP:
intervention
grou
p,mean(SD)
from
58.8
(26.02
)to
10.1
(6.28);con
trol,
from
49.5
(25.27
)to
46.4
(14.67
)(ANOVA
)
G0.00
1
AKA,
above-thekn
ee(transfemoral)ampu
tation
;ANOVA
,analysisofvariance;B
KA,
below-the-knee(transtibial)ampu
tation
;MPQ
-SP,
McG
illPain
Questionn
aire
Pain
IntensityScale;NRS,
numericrating
scale;
PLP,
phantom
limbpain;n
/a,n
otapplicable;R
CT,
rand
omized
controlledtrial.
4 Moura et al. Am. J. Phys. Med. Rehabil. & Vol. 91, No. 3, March 2012
neither met criteria for a high-quality clinical trial.Rickard’s38 study came closest to meeting criteria fora high-quality trial, but concealment of random al-location was unclear, and data regarding the com-parability of the groups at baseline was missing.38
In addition to these flaws, in the second RCT con-ducted by Chan et al.,19 the randomization methodwas inadequate, and it was unclear whether theassessments and analyses were blinded.19 Theauthors of this study also failed to report control ofother potentially confounding factors such as med-ication usage and other treatments being used by thepatients. Sample sizes of these studies were small(18Y20 subjects), and the studies were heteroge-neous in terms of both mind-body techniques andoutcomes. A third RCT was excluded because its pri-mary outcome was phantom limb sensation andawareness rather than PLP.39
Data SynthesisBecause of the small number of studies and
the heterogeneity of the mind-body techniques usedin the reports meeting our selection criteria, noquantitative synthesis of the findings was attempted.The following represents a summary of availablestudies examining mind-body techniques. To assistthe reader, the mind-body techniques are de-scribed briefly before the study reports. Tables 2Y5also present study elements for ease of comparisonacross studies.
RESULTS
HypnosisThe American Society of Clinical Hypnosis de-
fines hypnosis as Ba state of inner absorption, con-centration and focused attention.[52 Hypnosis isa form of information processing in which periph-eral awareness and critical analytic cognition aresuspended, readily leading to apparently involun-tary changes in perception, memory, and moodthat have profound behavioral and biologic con-sequences.53 Hypnosis has been used for more thana century as a therapeutic approach for a variety ofphysical and mental health conditions and is fre-quently cited in the literature as an effective mind-body intervention for pain.54 Numerous studiessuggest that hypnosis is effective as a primary oradjunctive treatment of acute pain related to med-ical and surgical procedures such as bone marrowaspiration, burn wound dressing changes, laborpain, and for chronic pain under conditions suchas fibromyalgia and headache.55 A review of con-trolled trials of hypnotic analgesia indicates that
hypnosis reduces pain better than no treatment atall for conditions such as headache, cancer-relatedpain, fibromyalgia, osteoarthritis, low back pain, anddisability-related pain.56 In 1996, the National In-stitutes of Health assembled a Technology Assess-ment Panel on the integration of behavioral andrelaxation approaches into the treatment of chronicpain and insomnia, which reported that relaxationand hypnosis are effective in reducing chronic pain.57
We identified a case report and review of casereports, one RCT, and one non-RCT in the use ofhypnosis as an adjuvant therapy for PLP. Reportsof cases indicate substantial improvement in PLPwith hypnosis training Table 2).30,38,40 In the smallclinical trial, patients 6 mos postamputation withPLP were randomized to either three individualsessions of hypnosis for PLP or the waitlisted con-trol group. Repeated-measures analysis of varianceshowed statistically significant time-by-group effects(P G 0.001) in the McGill Pain Questionnaire PainIntensity Rating and the Daily Pain Rating Scale. Inaddition, in the treatment group, prehypnotic paindecreased during the course of the three hypnosissessions.
In the only uncontrolled trial, a multifacetedintervention was used, including hypnotic analge-sia, visualization and movement of an imaginarylimb, psychologic hypnosis, and self-hypnosis.40 Inaddition to improvements in immediate presessionto postsession pain via Visual Analogue Scale, me-dian pain scores by nonparametric paired-sampletesting fell significantly. In his review of case re-ports, Oakley et al.30 proposed two types of hypnoticapproach to PLP using imageryVipsative/imageryand movement/imagery. The first one uses imagesto modify a patient’s representation of and to im-prove their pain; the second one uses suggestionsto make the patient move the phantom limb and tobe able to control the pain. In general, the studiesreduced pain frequency or intensity. Oakley et al.30
found no evidence that either form of hypnosis wassuperior to the other. As a whole, these case reportsand studies are suggestive of support for the use ofhypnosis as an effective intervention for PLP (andresidual stump pain) in the short term. Additionalwell-controlled randomized studies are needed be-fore conclusions can be made. It is particularly un-clear whether the positive effects of hypnosis onpain control are persistent.
Guided ImageryImagery is described as a thought process that
invokes and uses the senses: vision, audition, smelland taste, senses of movement, position, and touch.
It is considered a communication mechanism be-tween perception, emotion, and bodily change andis defined as using one’s imagination to createmental images that involve all senses to assist thebody in healing, maintaining health, or reducingstress and promoting relaxation.58Y60 A recent na-tional survey found that guided imagery was theninth most commonly used complementary andalternative medicine therapy (2.2%) by adults 18 yrsor older in the United States in 2007.61 InteractiveGuided Imagery is a unique form of guided im-agery created in a therapeutic setting as a resultof (1) patient/therapist interaction, (2) interactionbetween the patient and his or her images, and (3)interaction among the patient’s images.62 Duringan Interactive Guided Imagery session, initially,the patient was guided to a state of relaxation andencouraged to describe the spontaneous imagerythat happens at that particular moment. The ther-apist elicits the patient’s imagery and responds inan appropriate way. The Interactive Guided Im-agery session continues in an interactive and per-sonalized manner. It mobilizes the latent, innatehealing abilities of the patient to promote pain con-trol and accelerate rehabilitation, recovery, andhealth enrichment.62 The Interactive Guided Im-agery approach is eclectic, holistic, humanistic, andnondogmatic, incorporating skills from many re-lated disciplines including hypnosis, Jungian psy-chology, psychosynthesis, self-actualization, andego-state psychology.62
Imagery is thought to be helpful in a numberof conditions, including chronic pain, psychologicdistress, sleep disturbance, cancer, and cardiovas-cular disease.31,63,64 Our review identified fourstudies on imagery for persons with amputationexperiencing PLP: one case series and three un-controlled trials (Table 3).33,65Y67 These studiesused a variety of models of mental imagery in thetreatment of PLP in persons with amputation.Zuckweiler64 and Zuckweiler and Kaas67 used anovel imaging technique to increase the experienceof movement of the phantom limb. All patients inthe case series were free of pain at 6 mos after theconclusion of treatment. In the uncontrolled trial,PLP frequency diminished after treatment and at6 mos. In a second trial focused on central nervoussystem mechanisms, MacIver et al.33 used sensa-tion and movement imagery in combination withpsychotherapy and relaxation techniques. In addi-tion to demonstrating improvements in pain in-tensity, the investigators reported reductions incortical reorganization, a central nervous systemmechanism thought to cause PLP.33,68Y70 Instead
TABLE
3Mentalimagery
trainingforphantom
limbpainam
ongpersonswith
amputation
Case
Con
dition
Treatment
Results
P
McAvinu
eand
Rob
ertson
(201
1)65
case
series
(n=4)
PLP(AKA,
BKA1.7
to19
yrspreviously)on
40-yr-oldman,4
5-yr-old
man,
66-yr-oldman,and
25-yr-oldwom
an
Four
weeklysessions
ofmovem
entim
agerytraining
follo
wed
by6wks
training
onincreasing
the
awarenessof
theph
antom
andin
movem
ent
ofthestum
pandim
agined
movem
entof
the
phantom;d
aily
practice
andpain
diaries
Allp
articipantsim
proved
inim
ageryaftertraining
,althou
ghtwomorethan
theothers.T
hrou
ghinterrup
tedtimeseries
analysis,o
neof
the
four
participants
notedan
improvem
entin
PLP.
n/a
Zuckweiler(200
5)64
uncontrolledtrial
(n=14
)
PLP(leg,h
and,
finger1Y21
yrs
previously);71
%male,
aged
30Y80yrs
5to
15im
agerysessions
usingZIPS
over
4Y20
wks;
ZIPS
encourages
precisebo
dyim
ageandim
proved
mind-bo
dysensorymessaging
.
Sign
ificant
redu
ctionin
PLPfrequencyat
end
ofintervention
andat
6mos
(7-point
scale,W2 )
G0.00
1
MacIver
etal.(20
08)33
uncontrolledtrial
(n=13
)
PLPfor3Y51
yrs(arm
);11
men,3
wom
enSixtraining
sessions:g
uidedbo
dyscan
forrelaxation
follo
wed
bysensoryandmotor
imagerytraining
;participants
wereencouraged
topractice
daily
witha40
-min
CDanddo
a10
-min
exercise
tousewitho
utaCD.
Sign
ificant
decrease
inpain
intensity(NRS,
7.5
of10
to4.0of
10)andexacerbation
s(6.0
to3.0);
training
resulted
inredu
cedmotor
andsensory
cortical
reorganization
(inapp
ropriate
activation
ofcontralateralhand
/arm
cortical
area)by
fMRI
G0.00
1
Beaum
ontet
al.(20
11)66
uncontrolledtrial
(n=6)
PLPfor0.6Y
28yrs(arm
,AKA,
BKA);
allm
en,aged32Y65yrs
Participants
chose10
of48
movem
ents
from
avideoto
practice
withtheph
antom.T
raining
(30mins,twiceweekly)
over
4wks
added
twomovem
ents
perweekto
theinitial4.
Atho
me,participants
practiced30
minswith
avideoforan
addition
al4wks.
Imageryability
improved
inallb
uton
e.Fo
urparticipants
notedat
least30
%redu
ctionin
pain
aftertheintervention
,but
only
oneno
ted
persistenceof
theim
provem
entat
6mos
(witho
utpractice).Psycho
logichealth
appeared
tobe
afactor
indegree
ofim
provem
ent.
n/a
AKA,
above-thekn
ee(transfemoral)am
putation
;BKA,
below-the-knee(transtibial)am
putation
;fMRI,function
almagneticresonanceim
aging;
NRS,
numeric
rating
scale;PL
P,ph
antom
limbpain;n
/a,n
otapplicable;Z
IPS,
Zuckweiler’sIm
ageIm
printing
.
6 Moura et al. Am. J. Phys. Med. Rehabil. & Vol. 91, No. 3, March 2012
of cortical reorganization, Beaumont et al.66 mea-sured psychologic variables in investigating mech-anisms of reduction in PLP. The locus of control,social support, and general psychologic distresswerenegatively correlated with reductions in pain.66
Finally, in a study of visual mirror feedback, theinvestigators used mental imagery as a control con-dition.19 In the mental imagery condition, partici-pants in the study were instructed to imaginemovingtheir phantom rather than viewing the unaffectedlimb in a mirror. Visual stimulation with the mir-ror was superior in reducing PLP.19
BiofeedbackBiofeedback is a self-regulatory technique that
has been used for decades to help individuals learncontrol of autonomic physiologic processes, suchas heart rate, muscle tension, blood pressure, andvasoconstriction.71 The hypothesis is that the painexperience is maintained or exacerbated by auto-nomic nervous system deregulation.71 Biofeedbacksignals, which can be visual or auditory analogs ofthe physiologic changes, focus self-regulatory ef-forts. Biofeedback methods used to treat phantompain are many and include (1) electromyography, (2)muscle tension biofeedback, (3) thermal (periph-eral skin temperature) biofeedback, (4) visual mirrorfeedback, and (5) auditory biofeedback.71
Studies have shown that people experiencingPLP, especially those complaining of burning pain,present lower skin temperature at the stump distalend than at a corresponding point on the intactlimb.72Y74 Thermal biofeedback therapy, as pro-
mulgated by Sherman et al.,74 teaches PLP patientsto increase skin temperature at the stump distalend.74 In addition, patients with PLP presenting withspontaneous muscular hyperactivity in the stump,including involuntary spontaneous jerking, seemto benefit from electromyography biofeedback.75,76
Physiologically, when one autonomic nervous sys-tem function is regulated, such as skin temperature,it positively impacts other functions. For exam-ple, cold limbs indicate arteriolar vasoconstrictioncaused by increased sympathetic activation; in con-trast, warm limbs are a sign of arteriolar vasodila-tion as a result of decreased sympathetic drive andincreased parasympathetic activation. Sympatheticactivation, a common feature of anxiety and hyper-vigilance, is seen in a variety of chronic healthconditions, including chronic pain.71 Thermal bio-feedback, combined with simple relaxation tech-niques, trains PLP patients to both increase thetemperature of the stump and to relax.71 In time,repeated use of thermal biofeedback provides pa-tients with an increased ability to deal with stressand reduce pain.71
Two studies on traditional biofeedback treat-ment of PLP, a case report and an uncontrolledclinical trial, met our selection criteria (includingpublications after 1994) (Table 4).77,78 In the casereport, pain was completely resolved through acombination of electromyography and thermal bio-feedback.77 Despite earlier reports on the effec-tiveness of thermal biofeedback in some forms ofPLP, the uncontrolled trial did not show signifi-cant reductions in the primary outcome variable(McGill Pain Questionnaire Pain Intensity), but
TABLE 4 Biofeedback for phantom limb pain among persons with amputation
Case Condition Treatment Results P
Belleggia andBirbaumer (2001)77
case report (n = 1)
PLP (arm 3 yrspreviously);69-yr-old man
Six weekly EMG and thermalbiofeedback/relaxationsessions (1 hr), thensix weekly thermalbiofeedback sessions
Elimination of pain (VAS)at end of treatment,maintained at 3- and12-mo follow-ups, withdecreased differencesin EMG and temperaturebetween the stumpand the contralateral arm
n/a
Harden et al. (2005)78
uncontrolled trial(n = 9)
PLP (arm, leg); fivemen, four womenwith mean ageof 57.6 yrs
Six weeks of thermalautogenic biofeedbacksessions; follow-upat 12 mos
Only sensory MPQ-SPsignificantly differentbefore and after treatment;daily painintensity (VAS)reduced by mean of 39%
0.05
EMG, electromyography; MPQ-SP, McGill Pain Questionnaire Pain Intensity Scale; PLP, phantom limb pain; n/a, not appli-cable; VAS, Visual Analogue Scale.
McGill Pain Questionnaire sensory pain was signifi-cantly reduced.78
Visual Mirror Feedback and AssociatedTechniques
In the last 15 yrs, a novel approach to thetreatment of PLPVvisual mirror feedback (VMF)Vhas gained the attention of researchers in the fieldof rehabilitation medicine, with a proliferation ofclinical trials to study its effect on PLP in personswith amputation as well as its mechanism of ac-tion. Studies involving VMF are not limited to PLP;they also include complex regional pain syndrometherapy and stroke rehabilitation.63,79,80 In addition,new refined devices that use the same principles ofthe original cardboard visual mirror feedback box(virtual reality technology and left/right reversingprisms) have been developed.45,46,49,51
VMF is a technique introduced by Ramachandranand Altschuler81 in 1992 to treat pain of central ori-gin such as PLP. The VMF procedure requires the useof a rectangular box made of wood or cardboard. Amirror is placed vertically in the middle of the box,dividing it into two compartments, with the top andfront of the box removed. A patient places his/heraffected limb in one side of the box and the intactlimb in the other side. By looking at the intact limband its reflection on the mirror, patients observethat the intact limb visually takes the place of thephantom limb, creating an illusion that the phan-tom has been revived.41
In 1993, during his first experiment with VMF,Ramachandran and Altschuler81 observed that whilefacing a mirror box with open eyes and followingthe commanded movement of the intact limb, hispatient was able to see and feel the phantom limbmoving. During the course of the intervention, hispatient also had amarked reduction in pain intensity.The results of this experiment marked the beginningof a series of studies that contributed to advances inneurosciences’ Bnew view of brain functions[ andits Bstrong inter-sensory interaction as well as plas-ticity of the brain modules[ (p. 1693). Seven articleson VMF as an intervention for phantom pain metourselection criteria, along with three articlesusing virtual reality technology (Table 5).19,42Y51
The first set of investigations was carried out byRamachandran and Rogers-Ramachandran42 in1996 and reported again in 2009.81 Ramachandrandescribed a goal: to Bresurrect the phantom visuallyand study the inter-sensory effects of visual inputon phantom sensations[ (p. 377).42 Ten patientswith upper limb amputation, phantom limb sensa-
tion, and pain were treated with VMF followingan individualized protocol. The length of treatmentvaried from six single sessions of 5 mins to 15 minsa day for a few weeks. During and after the inter-vention, participants reported a reduction in pain,ability to move the frozen limb in the cases that thissensation was present, disappearance of the phan-tom arm in one of the patients, relief from spasmin the phantom arm, and touch perception in thephantom limb when the intact limb was touched.These experiments Bsuggest that there is an amountof latent plasticity even in adult human brain,[whereby Bprecisely organized new pathways, bridg-ing the two hemispheres, can emerge in less thanthree weeks.[(p. 386).42 As a result of his experi-ments, Ramachandran recommended imaging stud-ies such as functional magnetic resonance imagingand positron emission tomography scan to elucidatenew pathways of sensory interactions.
Three additional case reports were consistentwith Ramachandran’s initial findings. The resultsof the uncontrolled clinical trial of VMF were lessimpressive, demonstrating a 36% reduction in PLP.In the one small randomized trial, those who wereassigned to VMF achieved complete PLP resolutionas compared with 17% in the sham-mirror ther-apy and 33% in the Bmental visualization[ group.The virtual reality studies used an avatar createdby sensors either on the intact limb or the residuallimb. Improvements in pain control were similarto those reported using VMF therapy, althoughimprovement tended to decrease with time sincetreatment.45,49,51
DISCUSSIONAlthough more research is needed on specific
mind-body therapies to supply definitive evidenceof their usefulness for PLP, the weight of existingfindings indicates that a mind-body approach toPLP pain management is promising and that specificmethods may offer either temporary or long-termrelief, alone or in combination with conventionaltherapies. In particular, because conventional treat-ments are not always successful22,29,78 and may pro-duce unwanted adverse effects, it is important toconsider how mind-body therapies may enhancecare of PLP patients.
Relevance of Mind-Body Therapies toMechanisms of Action of PLP
To better understand the possible roles thatmind-body therapies may play in PLP management,it may be helpful to review the mechanisms of PLP.
Although answers regarding the causes of PLP haveremained elusive, much progress has been maderecently. It is now understood that multiple factorsinvolving both the central and peripheral nervoussystem contribute to PLP.82 Central factors involveboth the spinal cord and the brain. They includecentral sensitization in the spinal cord, character-ized by increased excitability, and expansion of re-ceptive fields into adjacent sensory areas.83 Inaddition, changes in input into the neural matrix-anetwork of neurons in several brain regions in-cluding the thalamus, somatosensory cortex, retic-ular formation, and limbic system together form ananatomical representation of self.84 Perhaps mostsignificantly, changes in the functional structuralarchitecture of the primary somatosensory cortexresult in phantom sensations arising from adjacentareas.81 For example, pursing of the lips resultedin activation of primary motor and sensory cor-tices corresponding to the phantom by functionalmagnetic resonance imaging,33 and greater corticalreorganization was associated with increased PLP.82
Peripheral nervous system changes includenociceptive input from the residual limb, as whena neuroma forms in the stump and peripheralneuropathy may contribute to worsening of pain.85
Paradoxically, stimulation of the stump throughdiscrimination training or myoelectric prosthesistends to reduce PLP.28 In addition, emotional fac-tors, including anger and stress, are known to ex-acerbate pain sensations in PLP, with both central(e.g., increased sympathetic nervous system activ-ity) and peripheral (e.g., muscle tensing and regionalsympathetic stimulation) factors being involved.78,86
Cognitive factors such as coping ability are also as-sociated with pain modification in PLP.83 It has alsobeen hypothesized that pain memories and proprio-ceptive memory may play a role in the character anddegree of PLP.33,87,88
In her first review, Flor83 stated that Bso far, fewmechanism-based treatments for PLP have beenproposed[ (p. 182). However, recent research in-dicates the potential for usefulness of several spe-cific mind-body therapies based on the relevanceof their mechanisms of action to those of PLP.For example, one of the most successful and well-studied therapies, Mirror Visual Feedback, appearsto target cortical reorganization,81 including changesin the somatosensory cortex and the neural matrix.Other therapies that use guided mental imagery,including therapeutic uses of hypnosis, may alsotarget reduction of cortical reorganization. For ex-ample, MacIver et al.33 found that motor imagerystimulated the contralateral cortex and reduced cor-
tical reorganization. Anderson et al.89 found thatmotor imagery was associated with activation ofthe thalamic sensory nuclei. Biofeedback mecha-nisms use the mind-body’s ability to self-regulate andrestore autonomic nervous system deregulation,71
as in the use of electromyography and thermalbiofeedback to decrease muscle tension and in-crease temperature of the stump, resulting in painmodification.77,78,90
Need for High-Quality Studiesof Mind-Body Therapies
A surprising finding in this literature reviewwas the paucity of research studies available inthe English language on mind-body therapies forphantom pain in persons with amputation. Onlystudies of hypnosis, imagery, and biofeedback, in-cluding visual mirror feedback, were found. Al-though the available findings are promising for therole of mind-body therapies, the articles reviewedhere have shortcomings that limit our ability togeneralize the findings, including small numbersof participants, uncontrolled experimental designs,and lack of study replication. There is a need forRCTs with well-defined and clearly reported treat-ment protocols to evaluate the efficacy of the vari-ous approaches that have been suggested, whetherthose approaches be hypnosis, imagery, or bio-feedback. Moreover, in this review, not all therapieswere used in a consistent and standard manner,which also affected the generalizability acrossstudies of the mind-body therapies. There is also aneed for standardized measures of the PLP to betaken preintervention and postintervention, alongwith other measures of psychologic and social ad-justment. With these caveats in mind, there is anoverall need for replication and validation of prom-ising findings in hypnosis, guided imagery, and bio-feedback. In addition, extended follow-up to measurechanges in quality and intensity of pain over time,as well as in-depth interviews of study participantsfor qualitative analysis of their experience, areadvisable.
One exception, in terms of volume of stud-ies, is those on VMF. The growing exploration andpromising findings for VMF lend support for its usein rehabilitation centers, either alone or in combi-nation with other mind-body therapies. Moreover,the value of VMF cannot be separated from thecontext in which it was developed and has con-tributed to the expansion of the new understandingof brain functions and advances in neuroscience.Because early experiments in the late 1970s on the
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effects of amputation on somatosensory maps inadult mammals, the resurgence of interest in theclinical phenomena of phantom limbs and the de-velopment of the VMF device and therapy in theearly 1990s, many advances have been made in neu-roscience with evident benefit for many people withchronic neurologic disorders including PLP in per-sons with amputation.
Additional research investigating the useful-ness of other mind-body therapies for PLP shouldalso be explored. Specifically, mindfulness medita-tion, a cognitive and behavioral technique involv-ing the intentional self-regulation of attention topresent-moment experience91 has already shown tosignificantly lower stressVwell known to exacer-bate pain phenomenaVas well as ameliorate de-pression and anxiety, also associated with increasedpain.92 Moreover, mindfulness has been shown toreduce pain in specific conditions and to enhancecoping ability.92Y94 To our knowledge, there are nostudies of mindfulness for persons with amputa-tion, including those experiencing PLP. Additionalresearch using existing therapies not found in thisreview include possible sympathetic blocks usinghypnotic analgesia. Hypnotic analgesia may operateat the spinal cord level and may be compared withregional anesthesia.95
Overall, one major advantage of mind-bodytherapies as part of a comprehensive pain manage-ment program is the ability to enhance capacity forself-regulation and self-efficacy, which can increasequality-of-life. Offering techniques known to ex-pand these capabilities for those with disabilities iscritically important to the well-being of this popu-lation and their reintegration into society.
The understanding of the phenomena of phan-tom pain and sensations is now being articulated inthe science of rehabilitation, and the important roleplayed by mind-body therapies in the treatment ofthis condition is only now beginning to be appreci-ated. More and better research on mind-body thera-pies for PLP, including studies of mechanisms ofaction, will extend the frontiers of research in theneurosciences on interactions of brain, body, andbehavior and enhance health care and quality-of-lifefor this deserving population.
ACKNOWLEDGMENTS
We thank Dr. Kyu Hoon Lee for his invaluablecontributions to the literature review.
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