Chemokines are associated with both inflammatory and immune responses and play an important role in the pathophysiological process associated with
neuropathic pain following
peripheral nerve injury. Here, we investigated the involvement of peripheral keratinocyte-derived
chemokine (KC) in the pathogenesis of
neuropathic pain induced by the partial
ligation of the sciatic nerve (PLSN) in mice. PLSN increased KC levels and its
mRNA in both the sciatic nerve and spinal cord when compared with
sham-operated mice. In addition, PLSN-induced mechanical and
thermal hyperalgesia was prevented by systemic (i.v.) treatment with anti-KC antibody either at the time of surgery or on the 4th day after surgery. Also, intrathecal (i.t.) injection of anti-KC antibody prevented
mechanical hyperalgesia induced by PLSN when administered at the time of surgery or on the 4th day after surgery. Importantly, the intraneural (i.n.) injection of KC in the mouse sciatic nerve elicited long-lasting
mechanical hyperalgesia, which was prevented by the selective CXCR2 antagonist
SB225002. The established
mechanical hyperalgesia induced by KC was expressively reduced by the treatment with
gabapentin, a
drug widely used to treat
chronic pain in humans. Intraneural KC injection also caused neutrophil migration into the mouse sciatic nerve and the depletion of neutrophils, by pre-treating animals with
vinblastine, significantly reduced KC-induced
mechanical hyperalgesia. Similar results were obtained for the pre-treatment with
indomethacin, a non-selective COX inhibitor. We also demonstrated an increased level of
cytokines (IL-1β, IL-6, and MCP-1, but not TNF-α) after i.n. injection of KC in the mouse sciatic nerve. Together, these findings suggest a role for KC in the development of
neuropathic pain in mice by attracting neutrophils to the injured site and increasing the production of proinflammatory mediators. Therefore, strategies to inhibit the action or the release of this
chemokine could constitute a therapeutic tool for the management of
neuropathic pain in humans.