penilaian nyeri neuropatik

30 Curr Top Neurol Psychiatr Relat Discip. Vol 18, No. 2, June 2010

Jovin Z. et al.

REVIEW ARTICLE UDC 616.8-009.7-07

ASSESSMENT OF NEUROPATHIC PAIN AND CLINICAL EVALUATION OF PATIENTS WITH SUSPECTED NEUROPATHIC PAIN

PROCENA I KLINIČKA EVALUACIJA PACIJENATA SA SUSPEKTNIM NEUROPATSKIM BOLOM

Zita Jovin1, Milan Cvijanović1, Miroslav Ilin1, Aleksandar Kopitović1, Aleksandar Ješić1

Abstract: Pain is an unpleasant sensory and emotional experience associated with existing or potential damage to the tissue or that is experienced as such. According to the current defi nition, the term neuro-pathic pain refers to pain that occurs as a direct consequence of a lesion or disease aff ecting the somatosen-sory system. Neuropathic pain is particularly problematic for its severity, chronicity and resistance to com-mon analgesics. It aff ects around 2-3% of the general population, although the estimates vary widely. Eval-uation of neuropathic pain includes neurophysiological tests, skin biopsy, quantitative sensory testing, phys-ical examination and pain assessment. Neuropathic pain causes positive and negative symptoms and can occur spontaneously or following a provoking stimulus. A detailed medical history and thorough clinical evaluation aid localizing the damage to the neuraxis. Precise determination of localization, intensity, qual-ity and pattern of pain are of the utmost importance.

Key words: neuropathic pain, clinical evaluation

Sažetak: Bol je neprijatno senzorno i emocionalno iskustvo udruženo sa aktuelnim ili potencijalnim oštećenjem tkiva ili je doživljeno kao takvo. Prema poslednjoj defi niciji termin neuropatski bol odnosi se na bol koji nastaje kao direktna posledica lezije ili bolesti koja zahvata somatosenzorni sistem. Specijalno je problematičan zbog njegove jačine, hroniciteta i rezistentnosti na uobičajene analgetike. Oko 2-3% popu-lacije pati od njega, iako postoje različiti podaci. Vrlo je važna procena neuropatskog bola koja podrazu-meva neurofi ziološke testove, biopsiju kože, kvantitativno senzorno testiranje, fi zikalni pregled pacijenta i merenje bola. Uzrokuje pojavu negativnih i pozitivnih simptoma, spontanog i stimulusom izazvanog bola. Detaljna istorija bolesti, opsežan klinički pregled pomažu u lokalizaciji oštećenja unutar neuroaksisa. Vrlo je važno odrediti lokalizaciju, intenzitet, kvalitet i vremensku distribuciju bola.

Ključne reči: neuropatski bol, klinička evaluacija

1 Clinic of Neurology, Clinical Center of Vojvodina, Novi Sad, Serbia. Correspondence to: Zita Jovin,MD, Clinic of Neurology, Clinical Center of Vojvodina, Hajduk Veljka 1, 21000 Novi

Sad, Serbia, E-mail: [email protected]* Received: October 16, 2009; accepted June 6, 2010.

31Curr Top Neurol Psychiatr Relat Discip. Vol 18, No. 2, June 2010

Jovin Z. et al.

INTRODUCTION

Pain commonly originates from activation of pri-mary nociceptive aff erents by current or potential stimuli due to tissue damage and the processing of these activities within the nociceptive system. Pain is an unpleasant sensory and emotional experien-ce associated with an existing or potential damage to the tissue, or that is experienced as such.

Classifi cation of pain according to the pathogene-sis

nociceptive pain1. neuropathic pain2. psychogenic pain3. idiopathic pain4.

Classifi cation of pain according to durationacute pain 1. subacute pain 2. chronic pain3.

In addition, pain can be initiated by activity ge-nerated within the nociceptive system without an adequate stimulation of its peripheral sensory en-dings. Th is type of pain is called neuropathic.

DEFINITION

According to the current defi nition, the term ne-uropathic pain refers to pain occurring as a di-rect consequence of a lesion or disease aff ecting the somatosensory system. (1). Th e term „disea-se“ has replaced the previous term „dysfunction“ that was poorly defi ned and could be wrongly in-terpreted, including normal plasticity of the noci-ceptive system. Th e term „disease“, however, sug-gests an identifi ed disease process such as infl am-mation, autoimmune conditions, or chanalopathi-

es, whereas „lesion“ indicates macro- or micros-copically identifi ed damage. Th e restriction to the somatosensory system is required since disease or lesion of other parts of the nervous system may cause other pain types that should not be confu-sed with neuropathic pain, such as pain associated with spasticity and rigidity that is caused by acti-vation of nociceptive aff erents in the muscles (5).

Neuropathic pain is described as burning, sta-bbing and electrical. It can be constant, aching, and paroxysmal.

EPIDEMIOLOGY

Epidemiology of neuropathic pain has not been studied thoroughly yet, partly due to a wide range of associated conditions.

Chronic pain is not uncommon, although the pre-valence in adults varies widely, from 2%-40%. Chronic pain comprises a nociceptive and a ne-uropathic component and is oft en multifactorial. Th e estimated 3.75 million cases of chronic neu-ropathic pain in the USA include various condi-tions, such as cancer pain, pain due to spinal cord injury, lumbar pain and phantom pain. Approxi-mately 45% of patients registered in health care organizations in the USA have recurrent and per-sisting pain, from lumbar pain to facial pain, and more than 25% of pain clinic patients in Great Bri-tain have neuropathic pain syndromes. Neuropat-hic pain associated with diseases such as diabetes mellitus and herpes zoster has been most extensi-vely studied and described, however these condi-tions are not the main causes of neuropathic pain. Radiculopathy, which may be the main cause of many cases of lumbar pain, is likely the most co-mmon cause of pain originating in peripheral ner-ves. (4,5).


Jovin Z. et al.

Table 1 Clinical conditions associated with neuropathic pain

Central nervous system Peripheral nervous systembrain infarction – cortical and subcortical nerve compression/entrapment neuropathies spinal cord trauma traumatic nerve injurydemyelination ischemic neuropathies

syringomyelia and syringobulbia polyneuropathies (hereditary, metabolic, toxic, infl amma-tory, paraneoplastic, nutritional, vasculitic, infectious)

neoplastic and other compressive lesions plexopathies (neoplastic, autoimmune, postradiation, trau-matic)

trigeminal and glosopharyngeal neuralgia nerve root compressionmigraine* postamputation stump and phantom painfi bromyalgia* postherpetic neuralgia

cancer induced neuropathy (infi ltration, chemotherapy induced, radiation induced, surgically induced)

TYPES OF NEUROPATHIC PAIN

Neuropathic pain results from damage to the cen-tral and/or peripheral nervous system, an impen-ding impairment or dysfunction, frequently in the absence of pain producing impulses. Dama-ge to the nervous system causes loss of sensibili-ty (negative symptoms), where the degree of loss approximates with the severity of impairment. A minority of cases present with diff erent types of pain and dysesthesias (positive symptoms). Bloc-king of nerve conduction in neuropathic states ca-uses nerve dysfunction that can result in numb-ness, weakness and loss of deep tendon refl exes in

the area of the involved nerve. Neuropathic condi-tions also cause aberrant symptoms of spontaneo-us and provoked pain. Spontaneous pain (conti-nuous or intermittent) is commonly described as sharp, stabbing or burning. Pain provoked by a stimulus is characterized by hyperalgesia (increa-sed pain induced by painful stimuli) and allodynia (pain caused by non-painful stimuli), that result from mechanical, thermal or chemical stimulati-on. Th ese sensory abnormalities can spread outsi-de the nerve distribution, which can lead to a fal-se diagnosis of a functional or psychosomatic dis-order (6).

Table 2 Sensory symptoms and signs associated with neuropathic pain

Symptoms/signs

AllodyniaPain not caused by nociceptive stimulus (clothes, mild touch). Can be mechanical (e.g. mild pressure), dynamic (caused by non-painful stimulus shift ing), or thermal (caused by non-painful hot or cold stimuli)

Anesthesia Loss of normal sensitivity in the aff ected area Dysesthesia Spontaneous or provoked unpleasant abnormal sensation Hyperalgesia Exaggerated response to mild nociceptive stimulus Hyperpathy Delayed and explosive responses to nociceptive stimulusHypoesthesias Decrease in normal sensitivity Paresthesias Non-painful spontaneous abnormal sensation

Phantom pain Painful sensation of the presence of a limb that has been removed (e.g. amputated limb), or pain in the absence of current injury

ASSESSMENT OF PAIN

Pain is a complex experience dependent on cogni-tive, emotional and educational factors. It therefo-re demands tools that can measure it objectively. Th e following four degrees of ’objectivity’ can be

diff erentiated: 1. Laboratory tests that use quanti-tative means to measure objective response (neu-rophysiological tests and skin biopsy) 2. Quanti-tative sensory testing, which, although employing quantitative grading of stimuli, depends on the patient’s subjective assessment, 3. bedside evalu-


Jovin Z. et al.

ation that depends on the examiner’s experience and the patient’s ability and willingness to coope-rate 4. Pain questionnaires that depend entirely on patient’s responses (7).

NEUROPHYSIOLOGICAL TESTING

Standard neurophysiological responses to an elec-trical stimulus, such as nerve conduction studies and somatosensory evoked potentials (SEP), can identify, localize and quantify damage along perip-heral or central sensory pathways, however, they do not assess the function of nociceptive pathways (8). Th e leading approach currently is utilization of laser stimulators to emit heat-spreading impul-ses that selectively incite free nerve endings (Aδ and C) in the superfi cial skin layer. Consensus of over 200 studies currently accepts that laser- evo-ked potentials (Aδ- LEPs) are nociceptive respon-ses. Late LEPs enable simpler and much more reli-able neurophysiological assessment of the functi-on of nociceptive pathways and are useful in the diagnosis of the peripheral and central neuropat-hic pain (8). Th eir major drawback in the clinical practice is their limited availability. Ultralate LEPs (referring to activation of C fi bers) are technically much more diffi cult to record, and there are a few studies evaluating their usefulness in patients with neuropathic pain (9). Th e contact heat evoked po-tentials have been invented recently and still requ-ire clinical validation (10).

BIOPSY

Painful neuropathies typically and primarily af-fect small nerve fi bers. Early detection of small fi -ber neuropathy by nerve biopsy may be fruitless, since the assessment of small fi bers is troublesome and demands electronic microscopy. Percutaneo-us needle biopsy can quantify Aδ and C nerve fi -bers by measuring density of intraepidermal ner-ve fi bers (IENF). Damage to IENF is seen in vari-ous neuropathies that are characterized by small fi ber axonal loss. Percutaneous needle biopsy is simple, minimally invasive and optimal for follow up. However, despite these advantages, it is usele-ss in central pain and demyelinating neuropathies, and it is currently available only in several resear-ch centers (11).

QUANTITATIVE SENSORY TESTING (QST)

QST is analysis of perception in response to exter-nal stimuli of controlled intensity. Detection and pain thresholds are determined by applying sti-muli to the skin in an ascending and descending order of magnitude. Mechanical sensitivity for tactile stimuli is measured using plastic fi laments, pinprick sensation with weighted needles, and vi-bration sensitivity with an electronic vibrameter. Th ermal perception and thermal pain are measu-red using a probe that operates on a thermoelec-tric principle.

QST has been used for early diagnosis and follow-up of small fi ber neuropathies that cannot be asse-ssed by standard nerve conduction studies, and has proved useful in early detection of diabetic ne-uropathy. QST is particularly suitable for quanti-fi cation of mechanical and thermal allodynia and hyperalgesia and painful neuropathic syndromes, and it has been used in pharmacological studies of therapeutic effi cacy to provoked pain (5).

However, QST abnormalities do not provide a de-fi nite evidence of neuropathic pain, because QST shows changes also in non-neuropathic pain con-ditions, such as rheumatoid arthritis and infl am-matory arthromyalgias. QST is time-consuming and therefore diffi cult to perform in clinical prac-tice (5).

CLINICAL EVALUATION

A lot of symptoms, signs, and testing are needed in order to adequately and comprehensively defi -ne mechanisms involved in the development of a neuropathic pain syndrome. A detailed medical and surgical history is the fi rst step in understan-ding pain etiology. Th orough clinical examination allows the clinician to integrate the patient’s cu-rrent symptoms and start localizing the involved elements of the neuraxis. Identifying pain locali-zation, quality, intensity and pattern is of utmost importance. Neurological examination compri-ses simple tests for the assessment of presence or absence of specifi c stimulus-provoked signs. Eva-luation of sensibility, in particular in order to elicit hypoesthesia (numbness) or hyperesthesia (hyper-pathy and/or allodynia), should be done carefully.


Jovin Z. et al.

Diff erentiation between mechanical and thermal allodynia may have clinical signifi cance. Evaluati-on of refl exes, comprehensive motor studies and evaluation of the vegetative nervous system are necessary for understanding of neuropathy.

MEASUREMENT OF PAIN

Ancillary tools for assessment of pain characteri-stics are measuring instruments, i.e. pain scales, grading systems and questionnaires.

Unidimensional scales are based on self-asses-sment of pain, they are easy to use, effi cient and demand minimal eff ort from the examinee. Th ey disadvantage is the insuffi ciently defi ned upper li-mit.

Th e Numerical Rating Scale is commonly used sca-le. Patients are asked to rate their pain on a scale 0-10 or 0-5 (12).

Visual Analogue Scale is not suitable for older pa-tients with vision and cognitive defi cits Descriptive scale is used to grade pain using descriptors, such as no pain, mild pain, moderate, severe, extreme. If presented verbally, it is easily understandable even to patients with advanced stages of demen-tia (13).

Categorization scales enable patients to rate pain intensity using verbal or visual descriptors.

Continuous application of pain rating scales ena-bles monitoring therapeutic response, occurrence of new pain or worsening of existing pain (13).

Mutidimensional pain assessment involves appli-cation of a range of diff erent instruments (13).

Brief Pain Inventory (BPI) evaluates pain and the patient’s subjective assessment of the eff ects of pain of daily activities and function. McGill Pain Questionnaire (MPQ) enables rating multiple di-mensions of subjective experience (sensory, af-fective, evaluative) (13). Neuropathic Pain Scale (NPS) assesses eight qualities of neuropathic pain (sharp, dull, hot, cold, sensitive, itching, deep, su-perfi cial) and rates each with 0-10.

Depending on the purpose of measurement, i.e. general measurement of only chronic pain, mea-surement specifi c to certain pain syndrome or qu-ality of life, various instruments for multidimen-sional pain assessment have been designed (e.g. Randall Chronic Pain Scale, Ronald-Morris Disabi-lity Scale, Sickness Impact Profi le).

Over the recent years several screening methods for diff erentiation of neuropathic and nocicepti-ve pain have been accepted. Some of them, such as NPQ (Neuropathic Pain Questionnaire (14), ID Pain (15), i PainDETECT (20), employ only in-terview. Th e Leeds Assessement of Neuropathic Simptoms and Signs (LANSS) (16) and the Do-uleur Neuropathique en 4 Questions (DN4) (17) use both interview and various studies of tactile hypesthesia, soft touch pain, and these scales show better sensitivity and specifi city than former, whi-ch implies the signifi cance of clinical examinati-on.

CLINICAL EVALUATION OF PATIENTS WITH SUSPECTED NEUROPATHIC PAIN

PATIENT HISTORY

Pain intensity

Pain scales•

Assessed at each visit in order to monitor ther-• apeutic response

Description of sensory symptoms (18)

Quality of pain: • burning, sharp, stabbing, cold, allodynia (pain induced by a light touch of clothes or bed sheets)

Frequent non-painful sensations: pricking, tin-• gling, itching, numbness

Temporal variation

Neuropathic pain commonly becomes more • severe as the day advances (19)

If the pain severity progresses over months, a • neoplastic process should be suspected


Jovin Z. et al.

Functional impact

Impact on sleep (19), self-care, daily activities, • work, social and sexual function (20), mood and suicidal ideas (21)

Previous treatment

Neuropathic pain is usually resistant to acet-• aminophen and non-steroidal anti-infl amma-tory drugs (NSAIDs)

Adequate titrated doses of specifi c drugs • should be determined and documented

Alcohol and substance abuse

History of dependence disorders can aff ect the • decision about prescribing opioids and can-nabinoids

Previous dependence should be considered • with a psychologist and/or psychiatrist

Interaction of sedatives and alcohol and other • substances should be considered

CLINICAL EXAMINATION

Motor examination

Motor weakness can occur in the distribution • of the involved nerve

True weakness should be diff erentiated from • antalgic weakness

Deep tendon refl exes

May be decreased or absent in the distribution • of the aff ected nerve

Sensibility examination

Light touch, pin prick, vibration responses and • proprioception can be reduced or absent in the aff ected nerve territory

Sensory disturbance can expand outside the • nerve innervation territory

Dynamic allodynia (pain provoked by gently • brushing the skin with a cotton ball)

Th ermal allodynia (burning sensation in re-• sponse to an ice cube placed on the skin)

Hyperalgesia to a pin prick test (exaggerated • pain following a pin prick)

Pain on leg lift ing suggests irritation of lumbar • nerve rootsMyofascial trigger points confi rm existence of • myofascial pain along with neuropathicTinel’s sign (distally radiating paresthesias pro-• voked by tapping of damaged or regenerated nervous fi bers)

Skin examinationChanges in the skin temperature, color, sweat-• ing or hair growth suggest complex regional pain syndrome (CRPS) (22)Residual dermatomal scars may persist follow-• ing herpes zoster infectionSkin changes characteristic for diabetes melli-• tus

SPECIAL TESTS

CT and MRIFacilitate specifi c diagnosis (e.g. disk hernia-• tion, tumor infi ltration)

Electromyography and nerve conduction studies, other neurophysiological methods (SEP< LEP)Skin and nerve biopsy

Quantitative sensory testing

Th ree-phase bone scanMay facilitate diagnosis of CRPS (22)•

Laboratory testingAdditional tests to aid identifying causes of • neuropathies, e.g. Glucose tolerance test, thy-roid function, vitamin B12 levels, CD4+ T lymphocyte counts.

CONCLUSION

Th e cause of neuropathic pain oft en remains un-known despite thorough evaluation, and caution is needed before pronouncing pain idiopathic or psychogenic. Over the past years there have been huge advances in pain assessment.

Assessment of the patient with suspected neuro-pathic pain should be directed towards excluding treatable conditions (e.g. spinal cord compressi-


Jovin Z. et al.

on, neoplasms), confi rming the diagnosis of neu-ropathic pain and identifi cation of clinical fi ndin-gs (e.g. insomnia, autonomic neuropathy) that can facilitate establishing an adequate treatment.

References:

Treede RD, Jensen TS, Campbell JN, Cruccu G, 1. Dostrovsky JO, et al. Neuropathic pain: Redefi nition and a grading system for clinical and research purpos-es. Neurology 2008;70:1630–1635.

Max MB, Schafer SC, Culnane M, et al. Associa-2. tion of pain relief with drug side eff ects in posther-petic neuralgia: a single-dose study of clonidine, co-deine, ibuprofen, and placebo. Clin Pharmacol Th er 1988;43:363-71.

Fields HL, Rowbotham M, Baron R. Postherpet-3. ic neuralgia: irritable nociceptors and deaff erentation. Neurobiol Dis 1998;5:209-27.

Jensen TS, Gottrup H, Sindrup SH, et al. Th e clin-4. ical picture of neuropathic pain. Eur J Pharmacol 2001;429:1-11.

Cruccu G, Anand P, Attal N, Garcia-Larrea 5. L,Haanpaa M, et al. EFNS guidelines on neuropathic pain assessment. Eur J Neurol 2004;11:153–162.

Cruccu G, Aminoff MJ, Curio G, Guerit JM, Kaki-6. gi R, et al. Recommendations for the clinical use of so-matosensory-evoked potentials. Clin Neurophysiol 2008;119:1705–1719.

Garcia-Larrea L, Convers P, Magnin M, Andre´- 7. Obadia N, Peyron R, et al. Laser-evoked potential ab-normalities in central pain patients: Th e infl uence of spontaneous and provoked pain. Brain 2002;125:2766–2781.

Treede RD, Lorenz J, Baumgartner U. Clinical use-8. fulness of laser-evoked potentials. Neurophysiol Clin 2003;33:303–314.

Truini A, Galeotti F, Haanpaa M, Zucchi R, Al-9. banesi A, et al. Pathophysiology of pain in postherpet-ic neuralgia: A clinical and neurophysiological study. Pain 2008;140: 405–410.

Granovsky Y, Matre D, Sokolik A, Lorenz J, Casey 10. KL. Th ermoreceptive innervation of human glabrous and hairy skin: A contact heat evoked potential analy-sis. Pain 2005;115:238–247.

Lauria G, Cornblath DR, Johansson O, McArthur 11. JC, Mellgren SI, et al. EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy. Eur J Neuro 2005;l12:747–758.

England JD, Gronseth GS, Franklin G, Carter GT, 12. Kinsella LJ, et al. Evaluation of distal symmetric poly-neuropathy: Th e role of autonomic testing, nerve biop-sy, and skin biopsy (an evidence-based review). Muscle Nerve 2009;39:106–115.

American Pain Society; National Pharmaceutical 13. Council. Pain: Current Understanding of Assessment, Management, and Treatments. Continuing education program, 2006. Gleniev (IL): American Pain Society

Melzack R. Th e McGill Pain Questionnaire: Major 14. Properties and Scoring Methods. Pain 1975;1:277-99.

Freynhagen R, Baron R, Gockel U, Tolle T . Pain-15. DETECT: A new screening questionnaire to detect neuropathic components in patients with back pain. Curr Med Res Opin 2006;22:1911–1920.

Bennett MI. Th e LANSS Pain Scale: Th e Leeds As-16. sessment of Neuropathic Symptoms and Signs. Pain 2001; 92: 147–157.

Bouhassira D, Attal N, Alchaar H, Boureau F, Brux-17. elle J, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005;114:29–36.

Bouhassira D, Attal N, Alchaar H, Boureau F, Brux-18. elle J, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005;114:29–36.

Odrcich M, Bailey JM, Cahill CM, et al. Chronobi-19. ological characteristics of painful diabetic neuropathy and postherpetic neuralgia: Diurnal pain variation and eff ects of analgesic therapy. Pain 2006;120:207-12.

Smith MT, Haythornthwaite JA. How do sleep dis-20. turbance and chronic pain interrelate? Insights from the longitudinal and cognitive-behavioral clinical trials literature.Sleep Med Rev 2004;8:119-32.

Haythornthwaite JA, Benrud-Larsen LM. Psy-21. chological aspects of neuropathic pain. Clin J Pain 2000;16:S101-5.

Kozin F, Soin JS, Ryan LM, et al. Bone scintigraphy 22. in the refl ex sympathetic dystrophy syndrome. Radiol-ogy 1981;138:437-43.

Reviewer’s comment

Review article by Z. Jovin et al. cannot be better timed to raise our awareness about a diffi cult su-bject of neuropathic pain. Th ere is an urgent move to increase pain awareness throughout the world,


Jovin Z. et al.

from developed countries to developing countries. Immediately following the International Associa-tion of Pain Congress in Montreal , Canada, there will be a Pain Summit during the fi rst week of Sep-tember with wide participation, from practicing physicians, researchers, to drug companies and diff erent civic and political organizations. Th e re-ason is that pain patients are underdiagnosed and undertreated. For us neurologist it is even more urgent, as we frequently deal with patients com-plaining of pain associated with peripheral or cen-tral nervous disorders. Understanding of periphe-ral neuropathic pain is still legging new strides in areas of nociceptive pain. Central pain is even bi-gger enigma, especially with fi nding of dissociated sensory loss in post-stoke and spinal cord injury pain patients. Th ese fi ndings and resulting hypot-heses are against common sense of pathogenesis of usual pains-nociceptive pains. Th is is probably a main reason that there are no medications speci-fi cally developed to address this odd condition.

Th is excellent article comprehensively reviews the current state of the art defi nition, subtypes, and diagnostic approaches to neuropathic pain. It should help us better understand spectrum of ne-uropathic pain, choose a right diagnostic approa-ch and hopefully lead to a better management of these diffi cult to treat patients with chronic pains and dysesthesias. Logical next step would be a re-view article about treatment options in neuropat-hic pain, which is even more formidable task.

Aleksandar Beric, MD, D.Sc

Professor of Neurology, Neurosurgery and Orthopedic Surgery,

NYU School of Medicine, New York

penilaian nyeri neuropatik

Documents