PAIN�

151 (2010) 561–562

w w w . e l s e v i e r . c o m / l o c a t e / p a i n

Commentary

When does nerve injury hurt?

Although neuropathic pain is a consequence of a lesion in thesomatosensory system [6], not all lesions in the somatosensorysystem lead to neuropathic pain. Seemingly identical nerve injuriesor diseases may or may not lead to the experience of pain by theafflicted individual. Knowledge about the cofactors that contributeto whether or not a given nerve lesion is painful would thus bevery useful in the context of prevention and therapy. In this paper,Taylor and colleagues provide at least a partial answer to whatdetermines painfulness after a nerve lesion [5]. They studied 31 pa-tients with complete median or ulnar nerve transection or bothand surgical repair with a latency of at least one year after surgery.They found that 10 of the 31 patients had permanent pain, and thatthis group had less successful nerve regeneration, with more pro-nounced sensorimotor deficits compared to those without pain.Notably, even in the pain-free patients, nerve regeneration wason average still incomplete, and the differences in measures ofregeneration between the two groups were subtle. In animal mod-els, successful nerve regeneration is very closely related to the dis-appearance of pain behaviors [3]. Obviously, in humans, the matteris more complicated. While the difference in nerve regenerationwas significant on a group level, for several parameters, it wouldbe interesting to see the relationship between pain and the mark-ers for nerve regeneration on an individual basis.

Patients with pain also had lower cold tolerance, even in theunaffected hand. They had high catastrophizing and neuroticismscores, while the respective scores of the patients without painwere indistinguishable from those of the healthy controls. All thefactors identified by the authors to be related to pain are poten-tially of high clinical impact. However, the setting does not allowone to unequivocally distinguish among a causal trait inherent inthe patient, a circumstantial factor, or a factor that may be a con-sequence of the pain. Although the less complete regeneration ismost likely a factor related to the nerve injury itself and to the sur-gical success, there may in addition be an intrinsic factor in thepatient, promoting or not promoting nerve regeneration (for exam-ple, a genetic make-up that determines whether a person is a goodor a bad regenerators). As for diabetes [4], other co-factors inherentin the patient may contribute. The lower cold tolerance is morelikely to be an inherent trait of the patient, leading to an increasedsusceptibility to neuropathic pain, than to be a consequence of thenerve injury. On the other hand, it cannot be excluded that it mightbe caused by central sensitization following the chronic neuro-pathic pain that is produced by the injury. The paper again showshow difficult it is to draw conclusions as to cause–effect relation-ships when performing correlative studies.

0304-3959/$36.00 � 2010 International Association for the Study of Pain. Published bydoi:10.1016/j.pain.2010.07.010

The results of this study raise several new questions: Wouldthe catastrophizing and neuroticism scores already have beenhigh had they been tested before the nerve injury? The authorspostulate that neuroticism and pain catastrophizing contributeto hypervigilance and fear of movement, resulting in increasedsensory and motor impairments. This may indeed be the case,but there may also be other factors involved. Chronic distresscan lead to overactivity, followed, later, by unresponsiveness ofthe HPA-axis. The latter may, in turn, promote a pro-inflamma-tory profile [1], which itself is associated with increased pain[7]. Whether a neuro-inflammatory factor might be involved inthe type of patients included in the present paper remains tobe investigated. Would an early psychological intervention in pa-tients potentially at risk for neuropathic pain prior to peripheralnerve surgery be able to improve the outcome? Is the lack oflarge fiber-mediated central inhibition or the damage to C-fibernociceptors themselves the more important factor determiningpain? Could consequent early treatment targeting the motorimpairment in patients after nerve injury reduce the occurrenceof pain, in a manner analogous to mirror treatment for CRPS[2]? The paper by Taylor and colleagues has stimulated manyquestions that should be addressed with longitudinal studiesand with an interventional trial.

Acknowledgments

The author has no conflicts of interest relating to this commentary.

References

[1] Chrousos GP. Stress, chronic inflammation, and emotional and physical well-being: concurrent effects and chronic sequelae. J Allergy Clin Immunol2000;106:S275–91.

[2] Ezendam D, Bongers RM, Jannink MJ. Systematic review of the effectiveness ofmirror therapy in upper extremity function. Disab Rehab 2009;31:2135–49.

[3] Lindenlaub T, Sommer C. Partial sciatic nerve transection as a model ofneuropathic pain: a qualitative and quantitative neuropathological study. Pain2000;89:97–106.

[4] Polydefkis M, Hauer P, Sheth S, Sirdofsky M, Griffin JW, McArthur JC. The timecourse of epidermal nerve fibre regeneration: studies in normal controls and inpeople with diabetes, with and without neuropathy. Brain 2004;127:1606–15.

[5] Taylor KS, Anastakis DJ, Davis KD. Chronic pain and sensorimotor deficitsfollowing peripheral nerve injury. Pain 2010;151:582–91.

[6] Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, HanssonP, Hughes R, Nurmikko T, Serra J. Neuropathic pain: redefinition and a gradingsystem for clinical and research purposes. Neurology 2008;70:1630–5.

[7] Üçeyler N, Rogausch JP, Toyka KV, Sommer C. Differential expression ofcytokines in painful and painless neuropathies. Neurology 2007;69:42–9.

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562 Commentary / PAIN�

151 (2010) 561–562

Claudia SommerDepartment of Neurology, University of Würzburg, Germany

Address: Neurologische Klinik der Universität, Josef-Schneider-Str. 11,D-97080 Würzburg, Germany.

Tel.: +49 931 201 23763;fax: +49 931 201 23697.

E-mail address: sommer@mail.uni-wuerzburg.deReceived 6 July 2010

Accepted 13 July 2010