Chronic blockade of interleukin‐1 (IL‐1) prevents and attenuates neuropathic pain behavior and spontaneous ectopic neuronal activity following nerve injury

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.