Analysis of pain relief systems at peripheral sensory nerves

2020 Fiscal Year Final Research Report

• Project/Area Number: 17H03933
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Integrative animal science
• Research Institution: Tottori University
• Principal Investigator: KITAMURA Naoki 鳥取大学, 農学部, 准教授 (80301951)
• Co-Investigator(Kenkyū-buntansha): 保坂 善真 鳥取大学, 農学部, 教授 (00337023) ; 澁谷 泉 鳥取大学, 農学部, 教授 (50162649) ; 樋口 雅司 鳥取大学, 農学部, 講師 (70614791)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 疼痛 / 鎮痛 / アドレナリン作動系 / TRPV1 / noradrenaline / clonidine / capsaicin / 末梢神経

Outline of Final Research Achievements

We examined whether functional associations between adrenergic systems in peripheral sensory systems and TRPV1 caused analgesia. Although, nociceptive behaviors induced by capsaicin injected into rat hind paws were reduced by noradrenaline (NA) and clonidine, a selective α2 agonist, injected into the same site, they were not affected when adrenergic agents were injected into contralateral hind paws. Immunohistochemical experiments revealed α2 receptors and TRPV1 were co-expressed in the cell body of the primary sensory neurons. Electrophysiological capsaicin responses observed in isolated primary sensory neurons recorded by the patch clamp method were extensively inhibited by NA and clonidine, and these effects were inhibited by yohimbine, a selective α2 antagonist.
These results suggest that inhibition of TRPV1 activity by α2 adrenoceptors on sensory peripheral nerve terminals causes the analgesic effect.

Free Research Field

神経生理学

Academic Significance and Societal Importance of the Research Achievements

Clonidineなどのα2作働薬が鎮痛作用を示すことが知られていたが、その作用機序は不明であった。脊髄にはnoradrenalineに依る下降性疼痛抑制系という疼痛緩和システムが備わっており、α2作働薬もこれに作用すると考えられてきた。しかし本研究により、末梢感覚神経のレベルでα2受容体の活性化が、侵害受容神経繊維において痛み刺激を受容するとされているTRPV1チャネルの活性を抑制することで、末梢性に鎮痛作用を示しうることが明らかとなった。α2作働薬の主な作用は中枢性の鎮静作用であるが、末梢性の鎮痛作用が明らかになったことは、臨床上の薬物の選択や投薬方法の戦略構築の一助となる成果である。