A Critical Role for α7 Nicotinic Acetylcholine Receptor Signaling in Myeloid Lineage Cells in Chronic Neuropathic and Inflammatory Pain Responses

Neuroinflammation influences the development of chronic pain, an increasingly prevalent condition impacting the lives of many worldwide. Given the challenges of managing chronic pain, it is essential to explore new neuroimmune targets for the development of safe and effective analgesics. Alpha 7 nicotinic acetylcholine receptors (α7 nAChRs) have been explored for their role in pain and inflammation. We hypothesize that α7 nAChR expression within myeloid cells mediates an anti-inflammatory response that mitigates pain states. We engineered mice with deletion of the α7 gene (Chrna7) from myeloid lineage cells conditionally using LysM-Cre. We characterized these mice in chemotherapy-induced peripheral neuropathy (CIPN) using paclitaxel. RNA-sequencing and pathway enrichment analysis of spinal cord tissues from mice treated with paclitaxel were performed. Our study suggests α7 nAChR expression in myeloid cells mediates an endogenous cholinergic anti-inflammatory pathway, which plays a critical role in chronic neuropathic and inflammatory pain.