title: Chronic blockade of interleukin-1 (IL-1) prevents and attenuates neuropathic pain behavior and spontaneous ectopic neuronal activity following nerve injury.
abstract: Neuropathic pain is a chronic pain state resulting from peripheral nerve injury, characterized by hyperalgesia and allodynia. We have reported that mice with genetic impairment of IL-1 signaling display attenuated neuropathic pain behavior and ectopic neuronal activity. In order to substantiate the role of IL-1 in neuropathic pain, WT mice were implanted subcutaneously with osmotic micropumps containing either IL-1ra or vehicle. Two days following the implantation, two models of neuropathic pain were used; partial nerve injury (spinal nerve transection, SNT), or complete nerve cut (spinal neuroma model). Mechanosensitivity was assessed seven consecutive days following SNT, and on day 7 recordings of spontaneous ectopic activity were performed. In the spinal nerve neuroma model, autotomy scores were recorded up to 35 days. Vehicle-treated mice developed significant allodynia and autotomy, and clear ectopic activity (4.1±1.1% of the axons); whereas IL-1ra-treated mice did not display allodynic response, displayed delayed onset of autotomy and markedly reduced severity of autotomy scores, and displayed reduced spontaneous activity (0.8±0.4% of the axons). To test whether IL-1 is involved in maintenance of mechanical allodynia, a separate group of WT mice was treated with a single injection of either saline or IL-1ra four days following SNT, after the allodynic response was already manifested. Whereas saline-treated mice displayed robust allodynia, acute IL-1ra treatment induced long-lasting attenuation of the allodynic response. The results support our hypothesis that IL-1 signaling plays an important role in neuropathic pain and in the ectopic neuronal activity that underling its development.
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Dentistry and Medicine, Hebrew University, Jerusalem, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Gabay
authors.forename: Gilly
authors.initials: G
authors.lastname: Wolf
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shavit
authors.forename: Raz
authors.initials: R
authors.lastname: Yirmiya
authors.forename: Michael
authors.initials: M
authors.lastname: Tal
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009437:Neuralgia / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D010812:Physical Stimulation; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D013127:Spinal Nerves / Q000293:injuries* / Q000503:physiopathology
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1