Activation of alpha7 acetylcholine receptors reduces neuropathic pain by decreasing dynorphin A release from microglia

Dynorphin A is increased in neuropathic pain models. Activation of alpha 7 n acetylcholine receptor (nAchR) reduces inflammation and pain. Whether activation of alpha 7 nAchR affects dynorphin A release is unknown. The experiments evaluated the proinflammatory effect of dynorphin A in the spinal nerve ligation-induced neuropathic pain models and the effect of alpha 7 nAchR activation on the dynorphin A content. a alpha 7 nAchR agonist, PHA-543613 and its antagonist, methyllycaconitine citrate were used and dynorphin A content was measured after spinal nerve ligation and in microglia cultures to test the analgesic mechanisms of alpha 7 nAchR activation. The results showed that dynorphin A content peaked 3 to 7 days after nerve injury, and dynorphin A anti-serum intrathecal injection decreased IL-beta and TNF-alpha content a week after nerve injury. Activation of alpha 7 nAchR by PHA-543613 alleviated neuropathic pain behaviors and decreased dynorphin A concentration in the ipsilateral spinal cords. Also, PHA-543613 decreased dynorphin A release from the microglia cultures to LPS stimulation by activation of alpha 7 nAchR. Our results suggest that dynorphin A contribute to the development and maintenance of neuropathic pain and that decreasing dynorphin A content by activation of alpha 7 AchR of microglia is a potential therapeutic target for treating neuropathic pain.