Spinal interleukin-6 (IL-6) inhibits nociceptive transmission following neuropathy

Abstract

Interleukin-6 (IL-6) is a neuropoietic cytokine which is dramatically upregulated following peripheral nerve injury at the site of injury, in the dorsal root ganglion (DRG) and in the spinal cord. The functional effects of IL-6 in nociception in normal conditions and following nerve injury are unclear. Thus the aim of this study was to assess the effect of spinal IL-6 administration on nociceptive transmission in naive, sham-operated and neuropathic (spinal nerve ligation, SNL) rats using in vivo electrophysiology to elucidate the possible role of IL-6 in neuropathic pain. In anaesthetised rats, extracellular recordings were made from individual convergent dorsal horn neurones following electrical and natural (mechanical and thermal) stimulation of peripheral receptive fields. Exogenous spinal IL-6 (100-500 ng) had no significant effect on electrically evoked neuronal responses in naive rats. In contrast, following neuropathy, spinal IL-6 produced a dose-related inhibition of the electrically evoked C-fibre, initial C-fibre and measures of neuronal hyperexcitability (post discharge and wind-up). In addition, spinal IL-6 markedly inhibited mechanical neuronal responses in neuropathic rats. Higher doses of spinal IL-6 also inhibited, to a lesser degree, the initial C-fibre, post discharge and wind-up responses in sham-operated rats. These studies show that following nerve injury the actions of the cytokine alter so that spinal administration of IL-6 elicits anti-nociceptive effects not observed under normal conditions. Moreover, the inhibitory effects of IL-6 on C-fibre activity and neuronal hyperexcitability, suggest IL-6 to be a potential modulator of neuropathic pain.