Mechanisms of dysfunction of locus coeruleus in chronic neuropathic pain model

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K20080
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Gunma University
• Principal Investigator: Suto Takashi 群馬大学, 大学院医学系研究科, 助教 (60739621)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 青斑核 / 神経障害性疼痛 / 脳由来神経栄養因子 / 内因性鎮痛

Outline of Final Research Achievements

This study focused on the balance of excitatory/inhibitory neurotransmitter in the locus coeruleus in order to examine the functional change of locus coeruleus following peripheral nerve injury (SNL model). The balance was assessed by measuring the concentration of glutamate and GABA with in vivo microdialysis. At 6 weeks following nerve injury, the animals did not show pain induced analgesia that reflects a part of endogenous analgesia. In the locus coeruleus of the animals, glutamate did not increase even after painful stimulation. Five days repeated treatment with 7,8-dihydroxyflavone (BDNF receptor agonist) could reverse the dysfuction of locus coeruleus by decreasing GABA release after painful stimulation. The restoration resulted in enhancement of analgesic effect of pregabalin. Co-administration of 7,8-dihydroxyflavone with pregabalin could be a novel strategy to treat chronic neuropathic pain.

Free Research Field

麻酔科学