Role of cannabinoids in regulating nociceptive transmission in the rat spinal dorsal horn

大麻素在调节大鼠脊髓背角伤害性传递中的作用

• 批准号: 14580790
• 负责人: KUMAMOTO Eiichi
• 金额: $ 2.18万
• 依托单位: Saga University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580790/
• 关键词: Spinal cord; substantia gelatinosa; Pain; Nociceptive transmission; Anandamide; Cannabinoid; Synaptic transmission; Patch-clamp technique; グルタミン酸; 興奮性シナプス伝達

Nociceptive information is transmitted through. primary-afferent AS and C fibers to the spinal dorsal horn, particularly the substantia gelatinosa (SG), where this transmission is modulated by a variety of endogenous substances including cannabinoids. This research project examined the effects of cannabinoids on excitatory (glutamatergic) and. inhibitory. (GABAergic and glycinergic) transmission by applying the blind whole-cell patch-clamp technique to SG neurons of adult rat spinal cord slices. The following results were obtained : (1) an endogenous cannabinoid anandamide (ANA ;0.01-10μM), another endogenous cannabinoid arachidonoyl glycerol (2-AG ;20μM) and cannabinoid receptor agonist WIN 55,212-2 (WIN-2;5-10μM) did not change holding currents ; (2) monosynaptically-evoked Aδ-and C-fiber excitatory postsynaptic currents (EPSCs) were reduced in amplitude by ANA (10μM), 2-AG (20μM) and WIN-2 (5μM), the former inhibition was larger in extent than the latter one ; (3) these cannabinoids … More did not affect the amplitude and frequency of spontaneous EPSCs ; (4) ANA reduced the amplitude of electrically-evoked inhibitory postsynaptic currents (IPSCs) in a concentration range of 1-5 μM ; (5) a similar inhibitory action was induced by 2-AG (20μM) and. WIN-2 (5μM) ; (6) the inhibitory action produced by ANA (10μM) was anatgonized by a cannabinoid-receptor anatgonist SR141716A (5μM) ; (7) ANA (10μM) increased a paired-pulse ratio of the evoked IPSC amplitudes ; (8) ANA (10μM) reduced the frequency of spontaneous IPSC without a change in the amplitude.In conclusion, cannabinoids inhibit in SG neurons monosynaptic glutamatergic excitatory transmission. from the periphery and also GABAergic and glycinergic inhibitory transmission, all of which are due to the activation of cannabinoid receptors located in nerve terminals. Considering the expression of CBI cannabinoid receptors in the spinal dorsal horn, these actions are mediated by CBI receptors. It is suggested that such a CB 1 receptor activation may contribute to at least a part of antinociception produced by intrathecal administration of cannabinoids. Less

伤害性信息是通过。初级传入AS和C纤维到脊髓背角，特别是胶状质（SG），在那里这种传输是由各种内源性物质，包括大麻素调制。该研究项目检查了大麻素对兴奋性（兴奋性）和。抑制性的用全细胞膜片钳技术对成年大鼠脊髓片SG神经元进行了GABA能和甘氨酸能信号传递的研究。获得以下结果：（1）内源性大麻素anandamide（ANA ;0.01-10μM），另一种内源性大麻素花生四烯酸甘油（2-AG ;20μM）和大麻素受体激动剂WIN 55，212 -2（WIN-2;5-10μM）不改变保持电流;（2）ANA（10μM）、2-AG（20μM）和WIN-2（5μM）可降低单突触诱发的Aδ和C纤维兴奋性突触后电流（EPSC）的幅度;前者的抑制作用大于后者;（3）这些大麻素 ...更多信息 ANA在1-5 μM浓度范围内可降低电诱发的抑制性突触后电流（IPSC）的幅值; 2-AG（20μM）和. WIN-2（5μM）;（6）ANA（10μM）产生的抑制作用可被大麻素受体拮抗剂SR 141716 A（5μM）拮抗;（7）ANA（10μM）使诱发的IPSC幅值的成对脉冲比增加;（8）ANA（10μM）使自发IPSC频率降低而幅值无变化。以及GABA能和甘氨酸能抑制性传递，所有这些都是由于位于神经末梢的大麻素受体的激活。考虑到CBI大麻素受体在脊髓背角中的表达，这些作用由CBI受体介导。有人建议，这样的CB 1受体激活可能有助于至少一部分的抗伤害性产生的鞘内注射大麻素。少

项目成果

C.Luo, E.Kumamoto, H.Furue, J.Chen, M.Yoshimura: "Anandamide inhibits excitatory transmission to rat substantia gelatinosa neurones in a manner different from that of capsaicin."Neuroscience Letters. 321. 17-20 (2002)

C.Luo、E.Kumamoto、H.Furue、J.Chen、M.Yoshimura：“大麻素以与辣椒素不同的方式抑制大鼠明胶质神经元的兴奋性传递。”《神经科学快报》。

Ceng Luo: "Anandamide inhibits excitatory transmission to rat substantia gelatinosa neurones in a manner different from that of capsaicin"Neuroscience Letters. 321. 17-20 (2002)

曾洛：“大麻素以与辣椒素不同的方式抑制大鼠胶质神经元的兴奋性传递”《神经科学快报》。

L.-J.Lao, E.Kumamoto, T.Fujita, C.Luo, H.Furue, M.Yoshimura: "Cellular mechanisms for the. inhibition by adenosine of pain transmission in the spinal dorsal horn."Pain Research. 17. 63-68 (2002)

L.-J.Lao、E.Kumamoto、T.Fujita、C.Luo、H.Furue、M.Yoshimura：“腺苷抑制脊髓背角疼痛传递的细胞机制。”疼痛研究。

Y.Kawasaki, E.Kumamoto, H.Furue, M.Yoshimura: "α2 Adrenoceptor-mediated presynaptic inhibition of primary afferent glutamatergic transmission in rat substantia gelatinosa neurons."Anesthesiology. 98. 682-689 (2003)

Y. Kawasaki、E. Kumamoto、H. Furue、M. Yoshimura：“α2 肾上腺素受体介导的大鼠胶质神经元初级传入谷氨酸传递的抑制”98. 682-689 (2003)。

Y.Kawasaki: "α2 Adrenoceptor-mediated presynaptic inhibition of primary afferent glutamatergic transmission in rat substantia gelatinosa neurons."Anesthesiology. 98(3). 682-689 (2003)

Y. Kawasaki：“α2 肾上腺素受体介导的大鼠胶质神经元初级传入谷氨酸传递的抑制。”麻醉学 682-689。