Alsharari_2013_Biochem.Pharmacol_86(8)_1201

A growing body of evidence indicates that alpha7 nicotinic receptor subtypes play an important role in chronic inflammatory and neuropathic pain signaling. In the present study, we investigated the role of the endogenous alpha7 nicotinic receptors (nAChRs) signaling in pain and inflammation using transgenic mice. For that we evaluated pain-related behaviors in the alpha7 mutant mice (KO) and its complementary alpha7 hypersensitive mice (KI) expressing the L250T alpha7 nAChRs and their respective WT mice in acute, chronic inflammatory and neuropathic mouse models. alpha7 KO and KI mice showed no significant changes in pain responses evoked by acute noxious thermal and mechanical stimuli as compared with WT littermates. While alpha7 KO mice showed no alterations in thermal and mechanical allodynia compared to WT mice after chronic nerve injury in the CCI test, alpha7 KI mice showed a significant reduction in these pain-related responses. However, marked increase in edema, hyperalgesia, and allodynia associated with intraplantar CFA injection was observed in the alpha7 KO mice compared with the WT littermates. In contrast, alpha7 KI mice displayed lesser degree of hyperalgesia and allodynia after CFA injection. Finally, the ability of systemic nicotine to reverse already-developed mechanical allodynia produced by intraplantar CFA seen in WT mice was lost in the alpha7 KO animals. Overall, our results demonstrate that endogenous alpha7 nAChRs mechanisms play an important role in chronic inflammatory and neuropathic pain models. This provides an additional rationale for the utility of alpha7 nAChR agonists in the treatment of inflammatory and chronic pain.