Investigating the Role of Alpha-7 Nicotinic Acetylcholine Receptors in Myeloid Lineage Cells in Acute and Chronic Inflammatory Pain

Abstract ID 90358 Poster Board 097 Alpha-7 nicotinic acetylcholine receptors (α7-nAChRs) have been shown to play a role in pain and inflammation. These receptors are expressed in macrophages and other myeloid lineage cells, which mediate the endogenous cholinergic anti-inflammatory pathway in cultured immune cells leading to attenuation of excess inflammation after insult. Animal models on the activation of α7-nAChRs with agonists show that receptor activation is antinociceptive and reduces local tumor necrosis factor activity and inflammation. However, the mechanism of α7-nAChR attenuation of inflammation is not fully understood. We hypothesize that α7-nAChRs expressed on myeloid cells play an important role in in vivo inflammation and nociception. This study examined the role of α7-nAChRs in acute and chronic inflammatory pain using conditional knock-out mice generated by Cre-loxP methodology in which α7-nAChRs are not expressed by myeloid cells, including macrophages. Male and female mice α7-Cre⁺ conditional knock-out (cKO) and α7-Cre⁻ (WT) were treated using either a plantar incision acute inflammation model or a CFA-induced chronic inflammation model and tested for thermal hypersensitivity and paw inflammation. Our results showed that α7-nAChR deletion in myeloid lineage cells did not have an impact on acute inflammation and hyperalgesia following paw incision. However, in the CFA chronic inflammation model we observed a significant increase in both the severity and time course of hyperalgesia and paw edema in α7-Cre⁺ cKO mice. Moreover, the antihyperalgesic effect of α7-nAChR silent agonists was lost in the α7-nAChR cKO mice. These results suggest that α7-nAChRs in myeloid cells are an important target in developing novel treatments for chronic inflammatory pain. Acknowledgments: This work was supported by NIH Grant R01CA206028 and the VCU School of Medicine Dean's Summer Research Fellowship.