Attenuating phosphorylation of p38 MAPK in the activated microglia: a new mechanism for intrathecal lidocaine reversing tactile allodynia following chronic constriction injury in rats.
Increasing evidences approve the long-term analgesia effects of intrathecal lidocaine in patients with chronic pain and in animal peripheral nerve injury models, but the underlying mechanism remains elusive. Previous evidences suggest that the activation of the p38 MAPK signaling pathway in hyperactive microglia in the dorsal horn of spinal cord involves in nerve injury-induced neuropathic pain. In this study, we demonstrate that attenuating phosphorylation of p38 MAPK in the activated microglia of spinal cord, at least partly, is the mechanism of intrathecal lidocaine reversing established tactile allodynia in chronic constriction injury model of rats. This finding not only provides a new insight into the mechanisms underlying long-term therapeutic effects of lidocaine on neuropathic pain, but also reveals one more specific drug target for analgesia.
Gu
Yi-Wen
YW
Department of Anesthesiology, Renji Hospital, Medical School of Shanghai Jiaotong University, 1630 Dongfang Road, Shanghai 200127, China.
Su
Dian-San
DS
Tian
Jie
J
Wang
Xiang-Rui
XR
D000779:Anesthetics, Local / Q000627:therapeutic use*; D000818:Animals; D003251:Constriction, Pathologic / Q000150:complications; D004195:Disease Models, Animal; D006941:Hyperesthesia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D007278:Injections, Spinal / Q000379:methods; D008012:Lidocaine / Q000627:therapeutic use*; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000201:enzymology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010147:Pain Measurement / Q000379:methods; D010523:Peripheral Nervous System Diseases / Q000150:complications* / Q000209:etiology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000779:Anesthetics, Local; D009419:Nerve Tissue Proteins; D008012:Lidocaine; D048051:p38 Mitogen-Activated Protein Kinases