Macrophage inflammatory protein-1α mediates the development of neuropathic pain following peripheral nerve injury through interleukin-1β up-regulation

Abstract

In the present study, we investigated the role of the macrophage inflammatory protein-1α (MIP-1α) in the pathogenesis of neuropathic pain following partial sciatic nerve ligation (PSL) in mice. MIP-1α mRNA and its protein were dramatically up-regulated after PSL, and MIP-1α was localized on macrophages and Schwann cells in the injured sciatic nerve (SCN). PSL-induced long-lasting tactile allodynia and thermal hyperalgesia were prevented by the perineural injection of anti-MIP-1α (2ng). Intraneural (20ng) and perineural (100ng) injection of recombinant MIP-1α elicited tactile allodynia and thermal hyperalgesia in sham-operated limb. MIP-1α receptors (CCR1 and CCR5) mRNA and their proteins were also up-regulated in the SCN after PSL, and were localized on macrophages and Schwann cells. PSL-induced tactile allodynia was attenuated by perineural injection (0.2nmol) of siRNA against CCR1 and CCR5. On the other hand, PSL-induced thermal hyperalgesia was prevented by siRNA against CCR5, but not CCR1. Interleukin-1β (IL-1β) mRNA and its precursor protein in macrophages and Schwann cells were also up-regulated in the SCN after PSL, and PSL-induced neuropathic pain was prevented by the perineural injection of anti-IL-1β (2ng). PSL-induced IL-1β up-regulation was suppressed by anti-MIP-1α and siRNA against CCR1 and CCR5. Perineural injection of nicotine (20nmol), a macrophage suppressor, prevented PSL-induced neuropathic pain and suppressed MIP-1α and IL-1β expressions. In conclusion, we propose a novel critical molecule MIP-1α derived from macrophages and Schwann cells that appears to play a crucial role in the development of neuropathic pain induced by PSL.