Chemokine Signaling and the Management of Neuropathic Pain

MCP1 as a chemokine in pain conditions. MCP1 may act at multiple sites and the precise nature of its involvement may differ in different pain conditions. (A) Schwann cells and/or endoneurial fibroblasts in injured axons upregulate MCP1, which then attracts macrophages into the nerve. Infiltrating macrophages may then secrete inflammatory molecules that sensitize the nerve. (B) Neurons in the DRG also upregulate both MCP1 and CCR2. The activation of CCR2 signaling in DRG neurons is excitatory and therefore pronociceptive. (C) DRG neurons may transport MCP1 to central nerve endings in the spinal cord where it is released. Once released in the spinal cord, MCP1 may activate secondary neurons and some CCR2⁺ leukocytes. Some neurons have been reported to express CCR2, and activation of CCR2 in these neurons may inhibit their response to GABAergic input (C).