一次求心性C線維の神経回路と機能的意義

1993 年度 実績報告書

• 研究課題/領域番号: 04255103
• 研究機関: 名古屋大学
• 研究代表者: 熊澤 孝朗 名古屋大学, 環境医学研究所, 教授 (20022775)
• 研究分担者: 堀 哲郎 九州大学, 医学部, 教授 (00022814) ; 東田 陽博 金沢大学, 医学部, 教授 (30093066) ; 成宮 周 京都大学, 医学部, 教授 (70144350) ; 佐藤 公道 京都大学, 薬学部, 教授 (80025709) ; 佐藤 昭夫 (財)東京都老人総合研究所, 自律神経部門, 副所長兼部長 (60072980)
• キーワード: 一次求心性C線維 / 痛覚 / 受容体クローニング / ブラジキニン / ブロスタグランジン / オピオイド / 神経伝達物質 / 細胞内シグナル伝達

研究概要

本年度の研究では、末梢及び中枢での痛みの伝達機構を電気生理学的、免疫組織学的、生化学的手法を用いて総合的に調べ、以下の結果を得た。課題7では、PGE_2によるポリモーダル受容器の熱反応増強効果はEP_2受容体を介し、cAMPを増大させて起こることを明らかにした(熊澤)。またBKのB_2受容体遺伝子をクローニングし、BKによりIP_3を介する過分極性のCa^<2+>流入機構をも見い出した(東田)。さらにPGE受容体サブタイプEP_1、EP_2の構造、分布、リガンド結合の特異性と情報伝達を明らかにし、痛覚に関与する後根神経節の小型ニューロンにEP_3受容体が発現していることを見い出した(成宮)。課題8では、体性感覚刺激により交感神経活動に反射電位が観察され、これはオピオイドμ-受容体により抑制されることを見い出した(佐藤昭)。課題9では、痛覚に関与する無髄神経線維の脊髄内終末はSP、CGRP陽性で(杉浦)、脊髄後角のGABA受容体分布は、膠様質ではB型が豊富で、第II、III層ではA型が優勢であることを見い出した(木村)。またμ-及びκ-オピオイド受容体cDNAをクローニングし、持続的疼痛により脊髄I、II層において、μ-及びκ-オピオイド受容体mRNAの発現量が多くなっているという知見を得た(佐藤公)。さらに脊髄視床路切断により視床のSP含有量が低下することより、SPが脊髄視床路の神経伝達物質の1つである可能性を見いだした(金澤)。課題10では、上腹部手術時の痛みストレスによる下垂体ホルモン分泌亢進は、上部頚椎レベルでの硬膜外麻酔により遮断されることを明らかにし(森)、IL-1βによる脳内の痛覚増強作用部位が、視床下部視索前野・前視床下部で、IL-1βの痛覚増強作用に関与するPGE_2はEP_3受容体を介することを明らかにした(堀)。

研究成果

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