1999 Fiscal Year Annual Research Report

In vivo パッチクランプ法による脊髄内痛覚伝達機序の解析

Research Project

Project/Area Number	10680766
Research Institution	Saga Medical School
Principal Investigator	吉村恵佐賀医科大学, 医学部, 教授 (10140641)
Co-Investigator(Kenkyū-buntansha)	古江秀昌佐賀医科大学, 医学部, 助手 (20304884)
Keywords	in vivoパッチクランプ / 下行性抑制系 / 慢性疼痛 / 痛覚過敏 / シナプス応答 / 皮膚刺激 / 膠様質細胞 / セロトニン
Research Abstract	新たに開発したin vivoパッチクランプ法を用いて、末梢皮膚に加えた機械的痛み刺激、熱刺激および非侵害性刺激によって誘起されるシナプス応答を脊髄後角細胞から記録解析した。後角膠様質細胞では、触刺激および機械的痛み刺激によってEPSCの頻度と振幅が著明に増大した。しかし、全ての膠様質細胞は、熱刺激には全く応答を示さなかった.膠様質より深層の細胞では、非侵害性刺激のみに応じる細胞、上記3種類の刺激に応じる、いわゆるWDRニューロンと触および機械的痛み刺激に応じる細胞の3種類が見いだされた。これらの感覚情報は何れもグルタミン酸仲介の速い経過のEPSCで伝達され、ペプチドを介する緩徐なシナプス応答は記録されなかった。次に、膠様質細胞のシナプス応答に対するセロトニン下行性抑制系の作用を検討した。脊髄表面に直接投与したセロトニンは触および痛み応答を共に抑制した。これらの作用は、脊髄スライスに後根を付した標本を用いて得られた結果、すなわち、痛みを伝えるC線維の応答と体毛の動きを伝えると考えられるAδ線維刺激によるEPSCをセロトニンが抑制することとも良く一致した。正常ラット脊髄から得られた基礎的なシナプス伝達機序を基に、次に、慢性疼痛モデルの一つである卵巣摘出(SNT)ラットを用い、痛覚伝達系にどの様な可塑的変化が起こっているかをin vivoパッチクランプ法を用いて検討した。その結果、SNTラットでは末梢C線維ターミナルに発現しているセロトニン受容体数が減少し、C線維応答が有意に増大した。しかし、Aδ線維の応答は抑制を受けないことを見いだした。これは、セロトニン受容体結合実験の結果とも一致した。以上の結果から、SNTラットでは痛みを伝えるC線維終末のセロトニン受容体が減少し、下行性抑制系による痛みのコントロールが消失する。その事によって痛覚過敏が起こっている可能性が示唆された。

Research Products
(20 results)

All Other

All Publications (20 results)

[Publications] Baba,H: "Muscarinic facilitation of GABA release in substantia gelatinosa of the rat spinal dorsal horn."Journal of Physiology. 508・1. 83-93 (1998)
[Publications] 河野達郎: "ニューロパシックペイン基礎"LISA. 5. 988-996 (1998)
[Publications] Yang,K: "Capsaicin facilitates excitatory but not inhibitory synaptic transmission in substantia gelatinosa of the rat spinal cord"Neuroscience Letters. 255. 135-138 (1998)
[Publications] 吉村恵: "痛覚系の可塑性"神経研究の進歩. 42. 406-416 (1998)
[Publications] 吉村恵: "脊髄膠様質における痛覚伝達"ペインクリニック. 19. 65-74 (1998)
[Publications] 吉村恵: "アロディニアの機序"The Journal of the Japan Society of Pain Clinicians. 5. 104-111 (1998)
[Publications] Furue,H: "In vivo whole-cell recording analysis of nociceptive transmission in the rat spinal dorsal horn"Pain Research. 14. 73-79 (1999)
[Publications] Furue,H: "Responsiveness of rat substantia gelatinosa neurons to mechanical but not thermal stimuli revealed by in vivo patch clamp recording"Journal of Physiology. 521. 529-535 (1999)
[Publications] Kohno,T: "Action of opioids on excitatory and inhibitory transmission in substantia gelatinosa of adult rat spinal cord"Journal of Physiology. 518. 803-813 (1999)
[Publications] Nakatsuka,T: "Plastic changes in sensory inputs to rat substantia gelatinosa neurons following peripheral inflammation"Pain. 82. 39-47 (1999)
[Publications] Park,J-S: "Bicuculline-resistant Cl-dependent GABA response in the rat spinal dorsal horn"Neuroscience Research. 33. 261-268 (1999)
[Publications] Park,J-S: "Reorganization of the primary afferent termination in the rat spinal dorsal horn during post-natal development"Developmental Brain Research. 113. 29-36 (1999)
[Publications] Yang,K.: "Action of capsaicin on dorsal root-evoked synaptic transmission to substantia gelatinosa neurons in adult rat spinal cord slices"Brain Research. 830. 268-273 (1999)
[Publications] Kohno,T.: "Actions of midazolam on GABAergic transmission in substantia gelatinosa neurons of adult rat spinal cord slices"Anesthesiology. 92. 507-515 (2000)
[Publications] Syadomi,M.: "Presynaptic inhibition by baclofen of miniature EPSCs and IPSCs in substantia gelatinosa neurons of the adult rat spinal dorsal horn"Pain. (in press). (2000)
[Publications] Ataka,T.: "Baclofen inhibits more effectively C-afferent than Aδ-afferent glutamotergic transmission in substantia gelatinosa neurons of adult rat spinal cord slices"Pain. (in press). (2000)
[Publications] Yang,K.: "Capsaicin induces a slow inward current which is not mediated by substance P in substantia gelatinosa neurons of the rat spinal cord"Neuropharmacology. (in press). (2000)
[Publications] Baba,H: "Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (part 1): effects on axon terminals of GABAergic and glycinerg neurons"Anesthesiology. 92(2). 473-484 (2000)
[Publications] Baba,H: "Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (part 2): effects on somatodendritic sites of GABAergic neurons"Anesthesiology. 92(2). 485-492 (2000)
[Publications] 吉村恵: "脳機能の解明〜21世紀に向けて〜"九州大学出版会. (1998)

1999 Fiscal Year Annual Research Report

In vivo パッチクランプ法による脊髄内痛覚伝達機序の解析

Principal Investigator

吉村 恵 佐賀医科大学, 医学部, 教授 (10140641)

Research Products

[Publications] Baba,H: "Muscarinic facilitation of GABA release in substantia gelatinosa of the rat spinal dorsal horn."Journal of Physiology. 508・1. 83-93 (1998)

[Publications] 河野達郎: "ニューロパシックペイン基礎"LISA. 5. 988-996 (1998)

[Publications] Yang,K: "Capsaicin facilitates excitatory but not inhibitory synaptic transmission in substantia gelatinosa of the rat spinal cord"Neuroscience Letters. 255. 135-138 (1998)

[Publications] 吉村 恵: "痛覚系の可塑性"神経研究の進歩. 42. 406-416 (1998)

[Publications] 吉村 恵: "脊髄膠様質における痛覚伝達"ペインクリニック. 19. 65-74 (1998)

[Publications] 吉村 恵: "アロディニアの機序"The Journal of the Japan Society of Pain Clinicians. 5. 104-111 (1998)

[Publications] Furue,H: "In vivo whole-cell recording analysis of nociceptive transmission in the rat spinal dorsal horn"Pain Research. 14. 73-79 (1999)

[Publications] Furue,H: "Responsiveness of rat substantia gelatinosa neurons to mechanical but not thermal stimuli revealed by in vivo patch clamp recording"Journal of Physiology. 521. 529-535 (1999)

[Publications] Kohno,T: "Action of opioids on excitatory and inhibitory transmission in substantia gelatinosa of adult rat spinal cord"Journal of Physiology. 518. 803-813 (1999)

[Publications] Nakatsuka,T: "Plastic changes in sensory inputs to rat substantia gelatinosa neurons following peripheral inflammation"Pain. 82. 39-47 (1999)

[Publications] Park,J-S: "Bicuculline-resistant Cl-dependent GABA response in the rat spinal dorsal horn"Neuroscience Research. 33. 261-268 (1999)

[Publications] Park,J-S: "Reorganization of the primary afferent termination in the rat spinal dorsal horn during post-natal development"Developmental Brain Research. 113. 29-36 (1999)

[Publications] Yang,K.: "Action of capsaicin on dorsal root-evoked synaptic transmission to substantia gelatinosa neurons in adult rat spinal cord slices"Brain Research. 830. 268-273 (1999)

[Publications] Kohno,T.: "Actions of midazolam on GABAergic transmission in substantia gelatinosa neurons of adult rat spinal cord slices"Anesthesiology. 92. 507-515 (2000)

[Publications] Syadomi,M.: "Presynaptic inhibition by baclofen of miniature EPSCs and IPSCs in substantia gelatinosa neurons of the adult rat spinal dorsal horn"Pain. (in press). (2000)

[Publications] Ataka,T.: "Baclofen inhibits more effectively C-afferent than Aδ-afferent glutamotergic transmission in substantia gelatinosa neurons of adult rat spinal cord slices"Pain. (in press). (2000)

[Publications] Yang,K.: "Capsaicin induces a slow inward current which is not mediated by substance P in substantia gelatinosa neurons of the rat spinal cord"Neuropharmacology. (in press). (2000)

[Publications] Baba,H: "Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (part 1): effects on axon terminals of GABAergic and glycinerg neurons"Anesthesiology. 92(2). 473-484 (2000)

[Publications] Baba,H: "Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (part 2): effects on somatodendritic sites of GABAergic neurons"Anesthesiology. 92(2). 485-492 (2000)

[Publications] 吉村 恵: "脳機能の解明〜21世紀に向けて〜"九州大学出版会. (1998)

吉村恵佐賀医科大学, 医学部, 教授 (10140641)

[Publications] 吉村恵: "痛覚系の可塑性"神経研究の進歩. 42. 406-416 (1998)

[Publications] 吉村恵: "脊髄膠様質における痛覚伝達"ペインクリニック. 19. 65-74 (1998)

[Publications] 吉村恵: "アロディニアの機序"The Journal of the Japan Society of Pain Clinicians. 5. 104-111 (1998)

[Publications] 吉村恵: "脳機能の解明〜21世紀に向けて〜"九州大学出版会. (1998)