Genetic impairment of interleukin-1 signaling attenuates neuropathic pain, autotomy, and spontaneous ectopic neuronal activity, following nerve injury in mice

Gilly Wolf, Eran Gabay, Michael Tal, Raz Yirmiya, Yehuda Shavit*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

151 Scopus citations

Abstract

Peripheral nerve injury may lead to neuropathic pain, which is often associated with mechanical and thermal allodynia, ectopic discharge of from injured nerves and from the dorsal root ganglion neurons, and elevated levels of proinflammatory cytokines, particularly interleukin-1 (IL-1). In the present study, we tested the role of IL-1 in neuropathic pain models using two mouse strains impaired in IL-1 signaling: Deletion of the IL-1 receptor type I (IL-1rKO) and transgenic over-expression of the IL-1 receptor antagonist (IL-1raTG). Neuropathy was induced by cutting the L5 spinal nerve on one side, following which mechanical and thermal pain sensitivity was measured. Wild-type (WT) mice and the parent strains developed significant allodynia and hyperalgesia in the hind-paw ipsilateral to the injury compared with the contralateral hind-paw. The mutant strains, however, did not display decreased pain threshold in either hind-paw. Pain behavior was also assessed by cutting the sciatic and saphenous nerves and measuring autotomy scores. WT mice developed progressive autotomy, beginning at 7 days post-injury, whereas the mutant strains displayed delayed onset of autotomy and markedly reduced severity of the autotomy score. Electrophysiological assessment revealed that in WT mice a significant proportion of the dorsal root axons exhibited spontaneous ectopic activity at 1, 3, and 7 days following spinal nerve injury, whereas in IL-1rKO and IL-1raTG mice only a minimal number of axons exhibited such activity. Taken together, these results suggest that IL-1 signaling plays an important role in neuropathic pain and in the altered neuronal activity that underlies its development.

Original languageAmerican English
Pages (from-to)315-324
Number of pages10
JournalPain
Volume120
Issue number3
DOIs
StatePublished - Feb 2006

Bibliographical note

Funding Information:
This work was supported by a grant from the Israel Science Foundation – The Charles H. Revson Foundation (Grant No. 799/03) (R.Y. and Y.S.). This work was facilitated by the Leon and Clara Sznajderman Chair of Psychology (Y.S.). We thank Professor K. Iverfeldt for the IL-1raTG mice. M.T., R.Y., and Y.S. are members of the Hebrew University Center for Research on Pain.

Keywords

  • Allodynia
  • Autotomy
  • Ectopic discharge
  • Hyperalgesia
  • Interleukin-1
  • Neuropathic pain
  • Proinflammatory cytokines

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