PAIN 152 (2011) 22042205

www.elsevier.com/locate/pain

Commentary

A new denition of neuropathic pain

1. Introduction IASP has recently published a new denition of neuropathic pain according to which neuropathic pain is dened as pain caused by a lesion or disease of the somatosensory system (www.iasp-pain.org/resources/painDenition). This denition replaces the 17-year old denition that appeared in the Classication of Chronic Pain published by IASP in 1994 [7], which dened neuropathic pain as pain initiated or caused by a primary lesion, dysfunction, or transitory perturbation of the peripheral or central nervous system. Even though the denition has not been changed dramatically, there are two important changes in the new version: (1) the word dysfunction has been removed and (2) a lesion or disease affecting the nervous system has been specied to be a lesion or disease of the somatosensory system. 2. Background The history behind this change dates back several years with a long, and at times, heated debate about the inclusion of the term dysfunction [5]. Clinicians with neurological training and background have found it difcult to accept conditions in which symptoms and signs were not reected in abnormal neuropathophysiology. It is regarded as essential, particularly in the clinical neurological specialties, to examine and classify patients based on the topography of the lesion and the underlying pathology. The debate about including/excluding the term dysfunction initiated a meeting among a group of neurologists, neurosurgeons, and clinical and basic neurophysiologists, both members and non-members of IASP. This meeting, and a subsequent long correspondence, resulted in a consensus paper published in the journal Neurology in 2008 [9] focussing on how clinicians and clinical scientists distinguish neuropathic pain from nociceptive pain. The consensus group suggested that neuropathic pain should be dened as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system [9]. It is this criterion, which is the basis for the almost identical denition proposed by the IASP Taxonomy Committee, that was accepted by the IASP council. 3. Why a new denition of neuropathic pain? The reasons behind this change in the denition of neuropathic pain are: 1. Neuropathic pain is not a single disease, but a syndrome caused by a range of different diseases and lesions, which manifests as an array of symptoms and signs. The mechanisms underlying these different conditions are multiple. Some of the mechanisms are known, but many are not. Increased understanding of pain mechanisms should put us in a better position to treat patients and design rational treatment strategies. There has indeed been progress since the last update of the neuropathic pain denition 17 years ago. For example, primary erythromelalgia and paroxysmal extreme pain disorder are both rare pain conditions for which we had no explanation 10 years ago, and therefore pain associated with these could not then have been classied as neuropathic. It is now clear that both disorders are due to specic and separable mutations in the SCN9A gene that codes for one of the many subtypes of neuronal voltagegated sodium channels: the Nav 1.7 channel [1]. While these observations have not yet resulted in a specic or preventive treatment for the rare genetic pain states, there is now a clear target that can be addressed. Another pain condition that has seen progress is Fabrys disease, which can now be treated with enzyme replacement therapy [6]. Biomarkers for an inammatory component in neuropathic pain are also being discovered, and again, these may lead to new specic treatments. Other examples will certainly be added as our knowledge of diseases and their causes increases. 2. The other strength (although critics might say limitation) of the new neuropathic pain denition is that the lesion in the nervous system has to be within the somatosensory system [3]. This requirement means that lesions in the cerebellum or frontal cortices, for example, will not qualify as a lesion causing central neuropathic pain, unless future research establishes that these regions also belong to the somatosensory system. The classical conditions associated with central pain include stroke, multiple sclerosis, certain forms of spinal cord injury, and syrinx of the central canal in the brainstem or spinal cord. Does it matter how restrictive we are in the current approach? We maintain that it does make a difference. If clinical criteria are distinct and precise, then the door is open not only for studying the pathophysiology of the condition, but also its epidemiology, and for testing specic treatments. The benet of having welldened criteria for dening pain disorders is clearly demonstrated by the wealth of excellent studies in the headache area. 3. The current therapy for neuropathic pain is not satisfactory; more than two-thirds of neuropathic pain patients obtain insufcient pain relief, and this poor response is likely related to our failure to target relevant pain-generating mechanisms in individual patients [2]. Our understanding of underlying neuropathic mechanisms will not be improved by including pain conditions such as CRPS and bromyalgia in the neuropathic pain syndrome, because the mechanisms causing pain in these disorders are even more obscure than in the classical neuropathic pain conditions, where pathology can be demonstrated.

0304-3959/$36.00 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.pain.2011.06.017

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The lack of structural abnormalities in so-called dysfunctional states (bromyalgia, CRPS, vulvodynia, interstitial cystitis, etc.) prevents us from nding a relationship between structure and function, which is important in the study of a subjective experience such as pain. If some patients with these disorders are found to represent cases of small-ber neuropathies [4,8], then those patients would easily fall under the umbrella of neuropathic pain. By excluding bromyalgia and CRPS from the neuropathic pain syndrome does this imply a risk for not offering these patients a treatment otherwise approved for neuropathic pain? Antidepressants and gabapentinoids with an approved indication for neuropathic pain are nonspecic compounds with a general action on neuronal hyperexcitability. As neuronal hyperexcitability is a mechanism shared by many chronic pain conditions, including bromyalgia and CRPS, treatment with antidepressants and gabapentinoids should denitely not be withheld from patients with these dysfunctional conditions, certainly not because of the current change of the denition of neuropathic pain. 4. Consequence of a restrictive denition of neuropathic pain It may be argued that by excluding syndromes such as CRPS type 1 and bromyalgia from the neuropathic pain group, there is a risk of stigmatizing this group of patients as having a somatization disorder, one without a true and demonstrable abnormality, as opposed to the patients who have a real physical illness. First of all, as pain is dened as what a person experiences, by denition all pain is real and legitimate [7]. The clinical challenge is to identify and ameliorate the cause(s) of the pain, which may be tissue damage, damage to the bodys warning system, both, or neither. We are not doing the patients any good by giving them a diagnostic label for which there is no basis. To include patients suffering from disorders with unexplained mechanisms under a specic label in casu: neuropathic pain will only serve as a sleeping pillow instead of sharpening our diagnostic search and attempts to dissect the underlying mechanisms. Our approach as pain researchers should be consistent with the IASP mission, which is to study the conditions in depth. The new denition offers a platform for doing further research experimentally, clinically, and pharmacologically, so as to better understand neuropathic pain syndromes. Also, it is our hope that the new denition will raise further scientic awareness and thus be an additional step in the direction of keeping up the scientic momentum and moving us from the domain of beliefs into evidence. 5. Conclusion A denition of neuropathic pain is only useful if it distinguishes conditions in a clinically meaningful way. If the denition does not provide additional benet in terms of understanding and treating the condition(s), then there is no reason to keep it. Hopefully, the new denition of neuropathic pain will act as a stimulant to discuss the denition in more detail and provide input for studies that can be used to test the value of the denition.

Conict of interest statement The authors have no conicts of interest to report. References
[1] Dib-Hajj SD, Cummins TR, Black JA, Waxman SG. From genes to pain: Nav1.7 and human pain disorders. Trends Neurosci 2007;30:55563. [2] Finnerup NB, Sindrup SH, Jensen TS. The evidence of pharmacological treatment of neuropathic pain. Pain 2010;150:57381. [3] Haanp M, Attal N, Backonja M, Baron R, Bennett M, Bouhassira D, Cruccu G, Hansson P, Haythornthwaite J, Iannetti G, Jensen TS, Kauppila T, Nurmikko T, Rice A, Rowbotham M, Serra J, Sommer C, Smith B, Treede R-F. NeuPSIG guidelines on neuropathic pain assessment. Pain 2011;152:1427. [4] Lauria G, Hsieh ST, Johansson O, Kennedy WR, Leger JM, Mellgren SI, Nolano M, Merkies IS, Polydefkis M, Smith AG, Sommer C, Valls-Sol J. European Federation of Neurological Societies; Peripheral Nerve Society. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small ber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol 2010;17:90312. [5] Max MB. Clarifying the denition of neuropathic pain. Pain 2002;96:4067. [6] Mehta A, Beck M, Elliott P, Giugliani R, Linhart A, Sunder-Plassmann G, Schiffmann R, Barbey F, Ries M, Clarke JT. Fabry Outcome Survey investigators. Enzyme replacement therapy with agalsidase alfa in patients with Fabrys disease: an analysis of registry data. Lancet 2009;374:198696. [7] Merskey H, Bogduk N. Classication of chronic pain. Seattle, WA: IASP Press; 1997. p. 20513. [8] Oaklander AL, Rissmiller JG. Postherpetic neuralgia after shingles: an underrecognized cause of chronic vulvar pain. Obstet Gynecol 2002;99:6258. [9] Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Grifn JW, Hansson P, Hughes R, Nurmikko T, Serra J. Redenition of neuropathic pain and a grading system for clinical use: consensus statement on clinical and research diagnostic criteria. Neurology 2008;70:16305.

Troels S. Jensen Department of Neurology and Danish Pain Research Center, Aarhus University Hospital, Norrebrogade 44, Building 1A, DK-8000 Aarhus C, Denmark Tel.: +45 8949 4137; fax: +45 8949 3269 E-mail address: tsjensen@ki.au.dk Ralf Baron Sektion fr Neurologische Schmerzforschung und -therapie, Klinik fr Neurologie, Universittsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany Maija Haanp Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland Eija Kalso Department of Anaesthesiology, Pain Clinic, Helsinki University, Helsinki, Finland John D. Loeser Department of Neurological Surgery, University of Washington, Seattle, WA, USA Andrew S.C. Rice Pain Research Group, Imperial College London, Chelsea and Westminster Hospital Campus, London, UK Rolf-Detlef Treede Chair of Neurophysiology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany