Modulation of inflammatory pain in response to a CCR2/CCR5 antagonist in rodent model

C‑C chemokine ligand 2 (CCL2), previously referred to as monocyte chemoattractant protein‑1 (MCP‑1), a 78 amino acid secreted protein, belongs to the CC subfamily and controls the recruitment of monocytes, memory T‑cells and natural killer cells to sites of inflammation through its chemokine receptor. CCL2 binds to Chemokine receptor type 2 (CCR2), the receptor for CCL2, exclusively and with a high affinity. CCL2 has been implicated as an important mediator of several diseases, including multiple sclerosis, rheumatoid arthritis, diabetes, and atherosclerosis. We previously reported that a CCR2 antagonist reduced swelling and joint destruction in rat models of rheumatoid arthritis and nearly produced a complete resolution of symptoms in a mouse model of multiple sclerosis.[1] In addition, recent reports suggest that chemokines may play roles in the experience of pain.[2‑4] Indeed, Abbadie reported that CCR2‑deficient mice showed a decrease in paw lifting and licking in a formalin‑induced inflammation model. Furthermore, in response to nerve ligation, the persistent and marked up‑regulation of CCR2 mRNA was evident in the nerve and dorsal root ganglia.[5] These results suggest that CCL2 may contribute to both inflammatory and neuropathic pain states. In this study, we investigated whether our CCR2 antagonist might exhibit an anti‑nociceptive effect in animal models.