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Current Concepts of Current Concepts of Pain Management in Pain Management in

Rheumatological Rheumatological DisordersDisordersDr. Chit SoeDr. Chit Soe

Associate Professor, Department Associate Professor, Department of Medicineof Medicine

Member of British Society of Member of British Society of RheumatologyRheumatology

MBBS, MMed.Sc, MBBS, MMed.Sc, MRCP(UK).,Dr.Med.ScMRCP(UK).,Dr.Med.Sc

University of Medicine IIUniversity of Medicine II

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IntroductionIntroduction Pain is the chief symptom of the rheumatic Pain is the chief symptom of the rheumatic

diseases and main cause of disability diseases and main cause of disability The word pain is used for two separate but The word pain is used for two separate but

often related phenomena often related phenomena unpleasant sensory experience unpleasant sensory experience an emotional anguish an emotional anguish

(IASP) has defined pain as (IASP) has defined pain as ""an an unpleasant sensory and emotional unpleasant sensory and emotional experience associated with actual or experience associated with actual or potential tissue damage or described potential tissue damage or described in terms of such damagein terms of such damage".".

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I. Inflammatory arthritisI. Inflammatory arthritis: : SeropositiveSeropositive:: RA, Rheumatic arthritis, SLE, RA, Rheumatic arthritis, SLE,

Scleroderma, DermatomyositisScleroderma, DermatomyositisSeronegativeSeronegative:: Psoriasis, Reiter’s $, Reactive arthritis, Psoriasis, Reiter’s $, Reactive arthritis,

Gout.Gout.II. Osteoarthritis, SpondylosisII. Osteoarthritis, SpondylosisIII. Back painIII. Back pain:: InflammatoryInflammatory – Ankylosing – Ankylosing

spondylitis.spondylitis. Mechanical Mechanical – PID– PIDIV. Soft tissue disorderIV. Soft tissue disorder:: Regional pain disorder, Regional pain disorder,

tendinitis, bursitis, fibromyalgia, collagen diseasestendinitis, bursitis, fibromyalgia, collagen diseases

Apart from that, Rheumatologists are dealing with Apart from that, Rheumatologists are dealing with vasculitis like Wegener’s granulomatosis, vasculitis like Wegener’s granulomatosis, Polymyalgia rheumatica, and Osteoporosis.Polymyalgia rheumatica, and Osteoporosis.

WHO Classification of Rheumatological Diseases.

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Pathophysiology & Pathophysiology & Mechanism:Mechanism:

Two kinds of painTwo kinds of pain MechanismMechanism Two fiber systemTwo fiber system Pain sensitive structuresPain sensitive structures Why painWhy pain

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Diagnosis of PainDiagnosis of Pain

Pain is there whenever a Pain is there whenever a patient complains so .patient complains so .

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Two kinds of painTwo kinds of pain

Fast pain (1st pain) -bright, Fast pain (1st pain) -bright, sharp, localized sensationsharp, localized sensation

Slow pain (2nd pain)-dull, Slow pain (2nd pain)-dull, intense, diffuse unpleasant intense, diffuse unpleasant feelingfeeling

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MechanismsMechanisms

Chemical irritation (bradykinin, Chemical irritation (bradykinin, prostaglandins, histamine)prostaglandins, histamine)

Ischaemia (? Rise in H+ Ischaemia (? Rise in H+ concentration)concentration)

Tension or distension (Mechanical)Tension or distension (Mechanical) Direct effect on peripheral nerves Direct effect on peripheral nerves

(pressure, cut)(pressure, cut)The sense organs for pain are the naked The sense organs for pain are the naked

nerve endings found in almost every nerve endings found in almost every tissue of the body. tissue of the body.

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Fig. Sensory ReceptorsFig. Sensory Receptors

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Small myelinated A delta fibers (2.5 Small myelinated A delta fibers (2.5 um in diameter), conduction rate 12-um in diameter), conduction rate 12-30m/s, conduct fast pain.30m/s, conduct fast pain.

Unmyelinated C fibers (0.4-1.2 um), Unmyelinated C fibers (0.4-1.2 um), conduction rate 0.5-2m/s, conduct conduction rate 0.5-2m/s, conduct slow pain.slow pain.

Both fiber groups end in the dorsal Both fiber groups end in the dorsal horn.horn.

A delta fibers terminate on neurons in A delta fibers terminate on neurons in laminas I and V.laminas I and V.

C fibers terminate on neurons in C fibers terminate on neurons in laminas I and II.laminas I and II.

Two fiber systemTwo fiber system

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Fig. Detail of Entrances Fig. Detail of Entrances

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Some of the axons of Some of the axons of the dorsal horn the dorsal horn neurons end in the neurons end in the spinal cord and brain spinal cord and brain stem.stem.Others enter the Others enter the anterolateral system. anterolateral system. A few ascend in the A few ascend in the posterolateral portion posterolateral portion of the cord. of the cord. Pain activates 3 Pain activates 3 cortical areas: SI, SII cortical areas: SI, SII and cingulated gyrus and cingulated gyrus on the opposite side.on the opposite side.

Fig. 3 main sites of modulationPain Sensitive Structures

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Pain differs from other somatosensory Pain differs from other somatosensory modalities modalities

No adaptation to pain is observed in man and No adaptation to pain is observed in man and hyperalgesic states are a prominent feature of hyperalgesic states are a prominent feature of most painful pathological processesmost painful pathological processes

Pain receptors have a high threshold to most Pain receptors have a high threshold to most forms of stimulus corresponding roughly with forms of stimulus corresponding roughly with the degree of stimulus liable to injure the body.the degree of stimulus liable to injure the body.

The somatic deep structures vary greatly in The somatic deep structures vary greatly in their sensitivity to pain.their sensitivity to pain.

Some structures such as the subcutaneous Some structures such as the subcutaneous deep fascia, periosteum, joint capsules and the deep fascia, periosteum, joint capsules and the sheaths of nerves and blood vessels are highly sheaths of nerves and blood vessels are highly sensitive.sensitive.

Others, such as muscle, synovial membrane Others, such as muscle, synovial membrane and fat are generally less sensitive, while and fat are generally less sensitive, while articular cartilage and compact bone are articular cartilage and compact bone are apparently insensitive to pain. apparently insensitive to pain.

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Why Pain?Why Pain? ProtectiveProtective The protective role of pain is well illustrated The protective role of pain is well illustrated

by diseases such as tabes and syringomyelia by diseases such as tabes and syringomyelia Conversely an over-reaction to pain can Conversely an over-reaction to pain can

lead to excessive protection of the part lead to excessive protection of the part causing disuse atrophy; a mechanism that causing disuse atrophy; a mechanism that may operate in conditions such as Sudeck's may operate in conditions such as Sudeck's atrophy and the shoulder hand syndrome.atrophy and the shoulder hand syndrome.

The successful management of pain in The successful management of pain in patients clearly requires an understanding patients clearly requires an understanding must be based upon sound anatomical, must be based upon sound anatomical, physiological, pathological and physiological, pathological and psychological principles.psychological principles.

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Mechanism of Pain in Different Mechanism of Pain in Different Rheumatological DisordersRheumatological Disorders

Inflammatory ArthritisInflammatory Arthritis OA and spondylosisOA and spondylosis Low back pain (Mechanical, Root Low back pain (Mechanical, Root

pain)pain) Soft tissue rheumatismSoft tissue rheumatism

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I. Inflammatory ArthritisI. Inflammatory Arthritis

Main villains are B cell cheating T cell, T Main villains are B cell cheating T cell, T cell helping B cell with the support of cell helping B cell with the support of Macrophage having extension from Macrophage having extension from apoptosis.apoptosis.

Macrophage and fibrocyte with mutation Macrophage and fibrocyte with mutation in p53 because of free radical, switching in p53 because of free radical, switching acute inflammation to chronic disease. acute inflammation to chronic disease.

Final pro-inflammatory mediators are Final pro-inflammatory mediators are IL1, IL 6 and TNF.IL1, IL 6 and TNF.

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Fig. Vicious cycle of inflammationFig. Vicious cycle of inflammation

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Fig. Ecosanoid system of Fig. Ecosanoid system of painpain

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Who should get COX2IWho should get COX2I

Because of the price, not all the Because of the price, not all the patient with pain can not effort patient with pain can not effort COX2ICOX2I

But should be the preferred drug forBut should be the preferred drug for Patients over 60Patients over 60 Patients with history of PUPatients with history of PU Patients taking steroidPatients taking steroid Patients not tolerating COX1IPatients not tolerating COX1I

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Fig. Ecosanoid system of Fig. Ecosanoid system of painpain

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Better KnowledgeBetter Knowledge

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Soluble Receptor Constructs Bind and Soluble Receptor Constructs Bind and Neutralize Soluble TNF-Neutralize Soluble TNF- andand TNF- TNF-

but Not Membrane-bound TNF-but Not Membrane-bound TNF-

Soluble TNF-

Soluble TNF-

Receptor-bound TNF-

Soluble receptor

construct

Enbrel prescribing information.

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Monoclonal Antibodies Bind and Monoclonal Antibodies Bind and Neutralize Both Soluble and Neutralize Both Soluble and

Membrane-bound TNF-Membrane-bound TNF-

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Vicious circleVicious circle

Deep pain initiates reflex contraction Deep pain initiates reflex contraction of nearby skeletal muscles. of nearby skeletal muscles.

The steadily contracting muscles The steadily contracting muscles become ischaemic, and ischaemia become ischaemic, and ischaemia stimulates the pain receptors in the stimulates the pain receptors in the muscles. muscles.

The pain in turn initiates more spasm, The pain in turn initiates more spasm, setting up a vicious circle. setting up a vicious circle.

If acute pain is not treated effectively, If acute pain is not treated effectively, chronic pain syndrome will be resulted.chronic pain syndrome will be resulted.

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II. OA and SpondylosisII. OA and Spondylosis

Mechanical StressMechanical Stress

Fig. Position of the head, effect of gravity and strain on the neck muscles

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Fig. Muscle strain due to faulty Fig. Muscle strain due to faulty postureposture

Increased strain Increased strain cause muscle pain, cause muscle pain, later loss of later loss of cartilage, bony cartilage, bony injury, and injury, and osteophyte osteophyte formation, un-even formation, un-even articular surface articular surface and bone pain and bone pain occurs. occurs. At knee, called OA At knee, called OA knee. knee. But known as But known as cervical cervical spondylosis and spondylosis and lumbar spondylosis lumbar spondylosis in spines. in spines.

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Fig. Balancing ExerciseFig. Balancing Exercise

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Spondylosis (Degeneration Spondylosis (Degeneration of spine)of spine)

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Fig. Changes in OA KneeFig. Changes in OA Knee

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Fig. Cervical nerve rootFig. Cervical nerve root

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Fig. Cervical spine position Fig. Cervical spine position and nerve root compression and nerve root compression

Important to keep Important to keep the cervical spine the cervical spine in certain angel to in certain angel to keep the best place keep the best place for nerves.for nerves.

Correct Exercises Correct Exercises or collar are the or collar are the options.options.

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RECOMMENDATIONS RECOMMENDATIONS (Davidson 19E, p991; Goodman and Gilman 10E, p696)(Davidson 19E, p991; Goodman and Gilman 10E, p696)

StartStart with with IBUPROFENIBUPROFEN ((PARACETAMOLPARACETAMOL for elderly) for elderly)

ChangeChange to another NSAID if no to another NSAID if no improvement or intolerance after one improvement or intolerance after one weekweek

If the drug is effective, If the drug is effective, continuecontinue treatment, and reduce dose if possible treatment, and reduce dose if possible and and stopstop altogether when no longer altogether when no longer necessarynecessary

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RECOMMENDATIONSRECOMMENDATIONS (continued) (continued) NeverNever prescribe more than one NSAID at a time, prescribe more than one NSAID at a time,

as combination therapy increases side effectsas combination therapy increases side effects For patient with recognized risk of peptic For patient with recognized risk of peptic

ulceration, add ulceration, add OMEPRAZOLE OMEPRAZOLE or misoprostol or or misoprostol or use a use a COXIBCOXIB

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ROFECOXIBROFECOXIB Used for OA, acute pain in adults, Used for OA, acute pain in adults,

dysmenorrhea, RA. dysmenorrhea, RA. Side Effect: Hypertension (10%) and oedema Side Effect: Hypertension (10%) and oedema

(4%), headache (5%), diarrhoea (7%), back pain (4%), headache (5%), diarrhoea (7%), back pain (3%), skin rash, insomnia, muscle cramps and (3%), skin rash, insomnia, muscle cramps and renal damage. renal damage.

Interactions: Cimetidine increases AUC of Interactions: Cimetidine increases AUC of rofecoxib; rofecoxib may increase plasma level rofecoxib; rofecoxib may increase plasma level of methotrexate and theophylline. of methotrexate and theophylline.

Dosage: ORAL 12.5 mg O.D. suspension or Dosage: ORAL 12.5 mg O.D. suspension or tablet, max 25-50 mg/day. May be taken without tablet, max 25-50 mg/day. May be taken without regard to meals.regard to meals.

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CELECOXIBCELECOXIB Used for RA, OA . Use with caution in patient with Used for RA, OA . Use with caution in patient with

history of GI disease. history of GI disease. Side Effects: Headache (16%), oedema (2%), dyspepsia Side Effects: Headache (16%), oedema (2%), dyspepsia

(9%), abdominal pain (4%), back pain (3%), acute renal (9%), abdominal pain (4%), back pain (3%), acute renal failure and hepatitis, palpitation, insomnia, anxiety, failure and hepatitis, palpitation, insomnia, anxiety, depression, muscle cramps, sulpha allergydepression, muscle cramps, sulpha allergy

Interactions: It is metabolized by CYP2C9 & CYP3A4, Interactions: It is metabolized by CYP2C9 & CYP3A4, and inhibits CYP2D6. and inhibits CYP2D6.

Dosage: OA 200 mg/day in single dose or divided dose. Dosage: OA 200 mg/day in single dose or divided dose. RA 100-200 mg B.D. High dose should be taken with RA 100-200 mg B.D. High dose should be taken with food to increase absorption.food to increase absorption.

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Repairing roof rather than Repairing roof rather than mopping floormopping floor

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Large hydrated proteoglycan molecules surround on all sides and

attached to collagen fibrils scabfold

Sticky gel like molecule ,shape a Test tube brush

Hyaluronan,

link,

Aggrecan (keratan(glucosamine),chondroitin)

PROTEOGLYCANS

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Patho-physiology of OAPatho-physiology of OASusceptibility

HeredityGender/Hormonal status

Obesity(Osteoporosis-negative)

(Smoking-negative)

Aging

TraumaJoint shape

Usage-occupational-recreationalMechanical

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RecommendationRecommendation

Glucosamine and chondroitin should Glucosamine and chondroitin should be considered for long term optionbe considered for long term option

Health education for proper position Health education for proper position and optimal weight reduction is and optimal weight reduction is important more than pain killer important more than pain killer tabletstablets

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Fig. Foot pain due to Fig. Foot pain due to mechanical stress on planta mechanical stress on planta

fasciafascia Mechanical stress of Mechanical stress of

weight-bearing upon weight-bearing upon the two ground points the two ground points of contact with of contact with resultant stretch upon resultant stretch upon the fascia is the same the fascia is the same mechanism upon a mechanism upon a stringed bow that is stringed bow that is pressed in the pressed in the direction of the white direction of the white arrows causing tension arrows causing tension upon the string. upon the string.

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III. Low Back PainIII. Low Back PainPain from nerve trunks and rootsPain from nerve trunks and roots (PID, Osteoporotic compressed fracture, (PID, Osteoporotic compressed fracture,

cervical and lumbar spondylosis)cervical and lumbar spondylosis) Very complex clinical pictures may result from Very complex clinical pictures may result from

irritation of the main nerve trunks or their irritation of the main nerve trunks or their roots of origin. roots of origin.

may give diffuse deep pain of segmental may give diffuse deep pain of segmental distribution together with referred deep distribution together with referred deep tenderness and deep pain symptom complex in tenderness and deep pain symptom complex in exactly the same way as produced by a deep-exactly the same way as produced by a deep-lying muscle or joint :lying muscle or joint :

is accompanied by limitation of leg raisingis accompanied by limitation of leg raising

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Various noxious influences affect different Various noxious influences affect different nerve fibres in varying degree. nerve fibres in varying degree.

In the rheumatic diseases nerve lesions are In the rheumatic diseases nerve lesions are usually caused by pressure or vascular usually caused by pressure or vascular occlusion. occlusion.

This causes damage to touch and motor This causes damage to touch and motor fibres earlier than to pain fibres fibres earlier than to pain fibres

and gives a clinical picture of numbness and gives a clinical picture of numbness and tingling followed by burning skin pain and tingling followed by burning skin pain and hyperalgesia and hyperalgesia

together with loss of light touch and early together with loss of light touch and early muscular weakness. muscular weakness.

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The reverse is the case in diabetic The reverse is the case in diabetic neuropathy where sudomotor, neuropathy where sudomotor, vasomotor and pain fibres are vasomotor and pain fibres are predominantly affected; predominantly affected;

whereas in the neuropathy whereas in the neuropathy associated with carcinoma or lead associated with carcinoma or lead poisoning motor function is mainly poisoning motor function is mainly affected. affected.

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Features of Neuropathic Features of Neuropathic PainPain

-Burning, stabbing or pulsing pain-Burning, stabbing or pulsing pain - Spontaneous pain, without ongoing tissue - Spontaneous pain, without ongoing tissue

damagedamage - Pain in an area of sensory loss- Pain in an area of sensory loss - the presence of a major neurological deficit - the presence of a major neurological deficit

(e.g. spinal cord compression from osteoporotic (e.g. spinal cord compression from osteoporotic fracture)fracture)

- Pain in response to non-painful stimuli - Pain in response to non-painful stimuli (allodynia)(allodynia)

- increased pain in response to painful stimuli - increased pain in response to painful stimuli (hyperalgesia)(hyperalgesia)

- unpleasant abnormal sensations (dysaesthesias)- unpleasant abnormal sensations (dysaesthesias) - poor relief with opioids alone- poor relief with opioids alone

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Neuropathic painNeuropathic pain

The pain is "initiated or caused by a primary The pain is "initiated or caused by a primary lesion or dysfunction in the nervous system," lesion or dysfunction in the nervous system," and yet its cause is heterogeneous and and yet its cause is heterogeneous and commonly may be inflammatory (for example, commonly may be inflammatory (for example, post herpetic neuralgia), metabolic, or post herpetic neuralgia), metabolic, or ischaemic.ischaemic.

Specific drugs to control neuropathic pain are Specific drugs to control neuropathic pain are being developed on the basis of sodium channel being developed on the basis of sodium channel blockers. Drugs presently available act on blockers. Drugs presently available act on sodium channels sensitive to tetrodotoxin and sodium channels sensitive to tetrodotoxin and thus have widespread side effects in the heart thus have widespread side effects in the heart and central nervous system. and central nervous system.

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Drugs for neuropathic Drugs for neuropathic painpain

AmitryptalineAmitryptaline

CarbamazapineCarbamazapine

GabapentamGabapentam

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PIDPID

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PIDPID

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LBP due to muscle LBP due to muscle sprainsprain

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Low Back PainLow Back Pain non-steroidal anti-inflammatory drugsnon-steroidal anti-inflammatory drugs Recommended for short term relief of symptoms Recommended for short term relief of symptoms Potential harmful side effects Potential harmful side effects Choice not limited by type but side effects Choice not limited by type but side effects ActivityActivity Leads to less chronic disability Leads to less chronic disability Exercise therapy strongly recommended for Exercise therapy strongly recommended for

chronic low back pain chronic low back pain Helps patients return to work Helps patients return to work Evidenced based treatment for acute back pain Evidenced based treatment for acute back pain

rather than bed rest rather than bed rest

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Multidisciplinary pain clinicMultidisciplinary pain clinic Includes education, active exercises, relaxation, Includes education, active exercises, relaxation,

behaviour therapy behaviour therapy Improves long term outcomes measured by Improves long term outcomes measured by

function, pain, and time at work function, pain, and time at work

One important example based on clinical One important example based on clinical evidence is back pain where therapies have evidence is back pain where therapies have changed from bed rest to active movement. changed from bed rest to active movement.

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Pain due to osteoporotic Pain due to osteoporotic ##

AlandronateAlandronate HRTHRT Calcium and vit DCalcium and vit D

BMD

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IV. Soft tissue IV. Soft tissue RheumatismRheumatism

Mostly psycho-Mostly psycho-somatic. And somatic. And Diffuse. Diffuse.

Sleep disturbance Sleep disturbance causes tense causes tense muscles and muscles and results in pain like results in pain like pain in legs after pain in legs after prolonged driving.prolonged driving.

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Fig. Tender points in Fig. Tender points in fibromyalgiafibromyalgia

Feeling of something in throatReduced grip powerInsomniaAbdominal bloating

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Approach to a patient Approach to a patient with painwith pain The degree of disability and whether medical help is The degree of disability and whether medical help is

sought or not are also determined by the individual's sought or not are also determined by the individual's tolerance of pain; tolerance of pain;

a characteristic which is influenced by personal, a characteristic which is influenced by personal, ethnic and cultural factors and changes in the ethnic and cultural factors and changes in the individual life situation. individual life situation.

Descriptive Terms (Types Of Pain)Descriptive Terms (Types Of Pain)Verbal accounts of distribution can be misleading Verbal accounts of distribution can be misleading since the patient's concepts of anatomy are not the since the patient's concepts of anatomy are not the same as the physician's.same as the physician's.

For example 'pain in the hip' usually means pain felt in For example 'pain in the hip' usually means pain felt in the region of the iliac crest or great trochanter which the region of the iliac crest or great trochanter which often results from renal or spinal disease.often results from renal or spinal disease.

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Fig. VAPSFig. VAPS

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PainPain Localized or diffuseLocalized or diffuse Swelling present or notSwelling present or not Mono or PolyMono or Poly Acute or ChronicAcute or Chronic Axial or peripheralAxial or peripheral Small or BigSmall or Big Extra-articular featuresExtra-articular features Routine facts of history like Age, Sex, Routine facts of history like Age, Sex,

Occupation, Marietal status, family Occupation, Marietal status, family history, Drug history should not be left.history, Drug history should not be left.

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Mono-arthritis of acute onset (Gout)

Pain without significant swelling, chronic (OA)

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Axial joints (Spine and SI), (Ankylosing Spondylitis)

Polyarthritis, peripheral, small (RA)

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Peripheral, big joints (Rheumatic fever)

Extra-articular features (facial rash, alopecia) (SLE)

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Current ConceptsCurrent Concepts

Pain perception Pain perception is the sum of is the sum of complex sensory, complex sensory, emotional and emotional and cognitive cognitive processes, processes, represented by represented by the the biopsychosocial biopsychosocial model of pain.model of pain.

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Characteristics of HostCharacteristics of Host*Biological: genetic, sex, endogenous pain control*Biological: genetic, sex, endogenous pain control*Psychological: depression, coping, behaviour, *Psychological: depression, coping, behaviour,

CognitiveCognitive

PainPain

EnvironmentEnvironment*History*History

*Present disease*Present disease *Socialisation, *Socialisation, lifestyle, lifestyle, TraumasTraumas

*Cultural, *Cultural, expectation, expectation, upbringing, roleupbringing, role

Fig. A simple to complex phenomenonFig. A simple to complex phenomenon

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Considered as vital signConsidered as vital sign

After a crisis, controlling vital signs After a crisis, controlling vital signs includeinclude Blood pressureBlood pressure Heart rateHeart rate Respiratory rateRespiratory rate Conscious levelConscious level TemperatureTemperature Pain !!Pain !!

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Recent developments Recent developments A major change in pain management is a A major change in pain management is a

move from empirical therapies to a move from empirical therapies to a mechanism based approach mechanism based approach

New drug developments are targeting specific New drug developments are targeting specific receptor subtypes receptor subtypes

Pain assessment includes qualitative sensory Pain assessment includes qualitative sensory affective and quantitative sensory testing to affective and quantitative sensory testing to improve subgroup analysis and evidence improve subgroup analysis and evidence based treatment of heterogeneous disease based treatment of heterogeneous disease states states

Care is individualised, holistic, and organised Care is individualised, holistic, and organised through a multidisciplinary approachthrough a multidisciplinary approach

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AIMS of Management are to:

Educate the patient Control pain Optimize function Beneficially modify the disease

process Look at the social environment

and create best support

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