Spontaneous pain in partial nerve injury models of neuropathy and the role of nociceptive sensory cover

Pini Koplovitch, Anne Minert, Marshall Devor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Spontaneous pain is difficult to measure in animals. One proposed biomarker of spontaneous pain is autotomy, a behavior frequently observed in rats with complete hindpaw denervation (the neuroma model of neuropathic pain). A large body of evidence suggests that this behavior reflects spontaneous dysesthesic sensations akin to phantom limb pain or anesthesia dolorosa. After partial paw denervation, such as in the spared nerve injury (SNI) model of neuropathic pain, autotomy is rare. Does this mean that spontaneous pain is absent? We denervated hindpaws in two stages: SNI surgery completed 7 or 28. days later by transection of the saphenous and sural nerves (SaSu). Minimal autotomy was evoked by the first stage. But it started rapidly after SaSu surgery rendered the limb numb, much more rapidly than after denervation in a single stage (neuroma model). The acceleration was proportional to the delay between the two surgeries. This "priming" effect of the first surgery indicates that the neural substrate of autotomy, spontaneous neuropathic pain, was not initiated by the onset of numbness, but rather by the first, SNI surgery. But the animal's pain experience was occult. The saphenous and sural nerves provided nociceptive sensory cover for the paw, preventing the behavioral expression of the spontaneous pain in the form of autotomy. The results support prior observations suggesting that partial nerve injury triggers spontaneous pain as well as allodynia, and illustrate the importance of nociceptive sensory cover in the prevention of self-inflicted limb injury.

Original languageAmerican English
Pages (from-to)103-111
Number of pages9
JournalExperimental Neurology
Volume236
Issue number1
DOIs
StatePublished - Jul 2012
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by applied research grants from the Julius Oppenheimer Fund , the Hebrew University of Jerusalem-Yissum Ltd. and by the Hebrew University Center for Research on Pain . We thank Elad Bassat for help with the graphics and Yoni Nissenbaum for advice on statistics. The authors have no conflict of interests with regard to the material in this report.

Keywords

  • Animal models
  • Autotomy
  • Neuroma model
  • Neuropathic pain
  • SNI model
  • Sensory cover
  • Spontaneous pain

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