Interleukin-17 is involved in neuropathic pain and spinal synapse plasticity on mice.

Abstract

Neuropathic pain seriously affects people's life, but its mechanism is not clear. Interleukin-17 (IL-17) is a proinflammation cytokine and involved in pain regulation. Our previous study found that IL-17 markedly enhanced the excitatory activity of spinal dorsal neurons in mice spinal slices. The present study attempts to explore if IL-17 contributes to neuropathic pain and spinal synapse plasticity. A model of spared nerve injury (SNI) was established in C57BL/6J mice and IL-17a mutant mice. The pain-like behaviors was tested by von Frey test and dynamic mechanical stimuli, and the expression of IL-17 and its receptor, IL-17RA, was detected by immunohistochemical staining. C-fiber evoked field potentials were recorded in vivo. In the spinal dorsal horn, IL-17 predominantly expressed in the superficial spinal astrocytes and IL-17RA expressed mostly in neurons and slightly in astrocytes. The SNI-induced static and dynamic allodynia was significantly prevented by pretreatment of neutralizing IL-17 antibody (intrathecal injection, 2μg/10μL) and attenuated in IL-17a mutant mice. Post-treatment of IL-17 neutralizing antibody also partially relieved the established mechanical allodynia. Moreover, spinal long-term potentiation (LTP) of C-fiber evoked field potentials, a substrate for central sensitization, was suppressed by IL-17 neutralizing antibody. Intrathecal injection of IL-17 recombinant protein (0.2μg/10μL) mimicked the mechanical allodynia and facilitated the spinal LTP. These data implied that IL-17 in the spinal cord played a crucial role in neuropathic pain and central sensitization.