(343) Localized Sympathectomy Drives Macrophage Polarization to Reduce Chemotherapy-Induced Neuropathic Pain

Abstract

Chemotherapy-induced neuropathic pain (CINP) is a disabling condition affecting up to 80% of patients during treatment with antineoplastic drugs, including the frontline chemotherapeutic agent paclitaxel. There are no FDA-approved drugs to treat CIPN and many drugs that are used for the treatment of other neuropathic pain states have shown poor or no analgesic effect on CINP, which suggests unique mechanisms underlie CINP. Paclitaxel is a common drug for various solid cancers. However, it is often associated with neuropathic pain, which is generally localized in the distal extremities of the body and can persist for months or years after the end of the treatment. Although the exact mechanisms underlying paclitaxel CINP remain incompletely known, there are several line of evidence indicating that immune cells in dorsal root ganglia (DRGs) play critical roles in the development and progression of CINP. Interestingly, our recent study has shown that sympathetic innervation not only drives immune responses in organs such as the thymus, spleen and lymph nodes, but also orchestrates localized immune responses in DRGs maintaining inflammatory pain. Here, we report that localized “microsympathectomy” (mSYMPX) significantly reverses mechanical allodynia in male and female mice after paclitaxel. Mechanistically, the mSYMPX analgesic effect is driven by an anti-inflammatory polarization of macrophages and TGF-β1 signaling in DRGs. Thus, localized sympathetic blockade may offer a novel therapeutic approach for the clinical relief of CIPN.