PT - JOURNAL ARTICLE AU - Nian Gong AU - Qi Xiao AU - Bin Zhu AU - Chang-Yue Zhang AU - Yan-Chao Wang AU - Hui Fan AU - Ai-Niu Ma AU - Yong-Xiang Wang TI - Activation of Spinal Glucagon-Like Peptide-1 Receptors Specifically Suppresses Pain Hypersensitivity AID - 10.1523/JNEUROSCI.4703-13.2014 DP - 2014 Apr 09 TA - The Journal of Neuroscience PG - 5322--5334 VI - 34 IP - 15 4099 - http://www.jneurosci.org/content/34/15/5322.short 4100 - http://www.jneurosci.org/content/34/15/5322.full SO - J. Neurosci.2014 Apr 09; 34 AB - This study aims to identify the inhibitory role of the spinal glucagon like peptide-1 receptor (GLP-1R) signaling in pain hypersensitivity and its mechanism of action in rats and mice. First, GLP-1Rs were identified to be specifically expressed on microglial cells in the spinal dorsal horn, and profoundly upregulated after peripheral nerve injury. In addition, intrathecal GLP-1R agonists GLP-1(7–36) and exenatide potently alleviated formalin-, peripheral nerve injury-, bone cancer-, and diabetes-induced hypersensitivity states by 60–90%, without affecting acute nociceptive responses. The antihypersensitive effects of exenatide and GLP-1 were completely prevented by GLP-1R antagonism and GLP-1R gene knockdown. Furthermore, exenatide evoked β-endorphin release from both the spinal cord and cultured microglia. Exenatide antiallodynia was completely prevented by the microglial inhibitor minocycline, β-endorphin antiserum, and opioid receptor antagonist naloxone. Our results illustrate a novel spinal dorsal horn microglial GLP-1R/β-endorphin inhibitory pathway in a variety of pain hypersensitivity states.