Pharmacological inhibition of CXCR2 alleviates neuropathic pain by inactivating microglia in a rat L5 spinal nerve ligation model.

Peripheral nerve injury (PNI)-induced neuropathic pain is a prevalent and severe clinical problem. It has been shown that microglia-mediated neuroinflammation plays a crucial role in neuropathic pain. The present study investigated the abnormal expression of C-X-C motif chemokine receptor type 2 (CXCR2) in a rat L5 spinal nerve ligation (SNL) model and evaluated the role of SB225002, a specific antagonist of CXCR2, in repressing neuroinflammation and neuropathic pain. It was found that CXCR2 expression was significantly upregulated in the dorsal horn of L5-SNL rats compared with sham control. Moreover, CXCR2 expression was increased in spinal microglia of rats after L5-SNL. Based on these results, the present study further examined whether pharmacological inhibition of CXCR2 suppressed microglial activation and neuropathic pain. It was demonstrated that SB225002 treatment inhibited L5-SNL-induced microglia proliferation and activation. Furthermore, SB225002 also significantly suppressed the L5-SNL-induced pro-inflammatory response, as indicated by decreased production of tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in spinal cord tissues. The results indicated that SB225002 also significantly inhibited microglial cell viability and lipopolysaccharide-induced production of pro-inflammatory cytokines in cultured microglia. Functionally, SB225002 treatment effectively repressed mechanical and cold hypersensitivity after peripheral nerve injury. Collectively, the present results suggested that pharmacological inhibition of CXCR2 by SB225002 suppressed L5-SNL-induced neuroinflammation and neuropathic pain, thus offering a potential therapeutic strategy for neuropathic pain treatment.
Competing Interests: None.
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