Molecular basis of spinal glia/endothelium/neurons interaction as the mechanisms of development and maintenance of chronic pain

2015 Fiscal Year Final Research Report

• Project/Area Number: 25290016
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Hyogo Medical University
• Principal Investigator: Noguchi Koichi 兵庫医科大学, 医学部, 教授 (10212127)
• Co-Investigator(Renkei-kenkyūsha): YAGI Hideshi 兵庫医科大学, 医学部, 教授 (10303372) ; YAMANAKA Hiroki 兵庫医科大学, 医学部, 講師 (20340995) ; KOBAYASHI Kimiko 兵庫医科大学, 医学部, 講師 (70418961)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 神経障害性疼痛 / グリア / 脂質メディエーター / ニューロン

Outline of Final Research Achievements

Using rat neuropathic pain models, we found the following findings.
1. PGD2 produced by microglia is COX-1 dependent, and neurons in the spinal cord can receive PGD2 from microglia following peripheral nerve injury, suggesting a role of PGD2 signaling in mechanical allodynia. 2. We found the details of RhoA/ROCK pathway in spinal microglia in this model. It mediates p38 MAPK activation and morphological changes downstream of P2Y12/13 receptors in spinal microglia in neuropathic pain. 3. We found that increased artemin in peripheral tissues plays an important role on the regulation of TRPV1/A1 in DRG neurons in pathological conditions such as inflammatory and neuropathic pain. 4. Using electrophysiological method, we found leukotriene enhances NMDA-induced inward currents in dorsal horn neurons of the rat spinal cord after peripheral nerve injury. 5. We found that microglial TNF alpha is able to induce COX2 and PGI2 synthase expression in spinal endothelial cells during neuropathic pain.

Free Research Field

神経解剖学　疼痛基礎研究