CCR2 chemokine receptor signaling mediates pain in experimental osteoarthritis

• DOI: 10.1073/pnas.1209294110
• Publication Date: 2012-11-27T06:38:27Z
• Authors: Rachel E. Miller; Phuong B. Tran; Rosalina Das; Nayereh Ghoreishi...; Dongjun Ren; Richard J. Miller; Anne-Marie Malfait
• Keywords: CCR2; CCR1; Chemokine receptor CCR5

Osteoarthritis is one of the leading causes chronic pain, but almost nothing known about mechanisms and molecules that mediate osteoarthritis-associated joint pain. Consequently, treatment options remain inadequate replacement often inevitable. Here, we use a surgical mouse model captures long-term progression knee osteoarthritis to longitudinally assess pain-related behaviors concomitant changes in innervating dorsal root ganglia (DRG). We demonstrate monocyte chemoattractant protein (MCP)-1 (CCL2) its high-affinity receptor, chemokine (C-C motif) receptor 2 (CCR2), are central development pain associated with osteoarthritis. After destabilization medial meniscus, mice developed early-onset secondary mechanical allodynia was maintained for 16 wk. MCP-1 CCR2 mRNA, protein, signaling activity were temporarily up-regulated DRG at 8 wk after surgery. This result correlated presentation movement-provoked behaviors, which up Mice lack Ccr2 also allodynia, this started resolve from onwards. Despite severe structural damage equal wild-type mice, Ccr2-null did not develop In macrophages infiltrated by through contrast, macrophage infiltration observed mice. These observations suggest key role MCP-1/CCR2 pathway establishing