Activation of Spinal Glucagon-Like Peptide-1 Receptors Specifically Suppresses Pain Hypersensitivity
Activation of Spinal Glucagon-Like Peptide-1 Receptors Specifically Suppresses Pain Hypersensitivity
复制标题
脊髓胰高血糖素样肽 1 受体的激活可特异性抑制疼痛超敏反应
DOI：
10.1523/jneurosci.4703-13.2014
复制
发表时间：
2014-04-09
影响因子：
5.3
通讯作者：
Wang, Yong-Xiang
中科院分区：
文献类型：
--
作者：
Gong, Nian;Xiao, Qi;Wang, Yong-Xiang
本研究旨在确定脊髓胰高血糖素样肽-1受体（GLP-1 R）信号在大鼠和小鼠疼痛超敏反应中的抑制作用及其作用机制。首先，GLP-1 R被鉴定为在脊髓背角的小胶质细胞上特异性表达，并且在外周神经损伤后显著上调。此外，鞘内注射GLP-1 R激动剂GLP-1（7-36）可有效缓解福尔马林、外周神经损伤、骨癌和糖尿病诱导的超敏反应状态60- 90%，而不影响急性伤害性反应。GLP-1 R拮抗作用和GLP-1 R基因敲低可完全阻断艾塞那肽和GLP-1的抗过敏作用。此外，exenadine诱发β-内啡肽释放从脊髓和培养的小胶质细胞。小胶质细胞抑制剂米诺环素、β-内啡肽抗血清和阿片受体拮抗剂纳洛酮可完全阻止外激素抗异常性疼痛。我们的研究结果阐明了一种新的脊髓背角小胶质细胞GLP-1 R/β-内啡肽抑制途径在各种疼痛超敏反应状态。
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.