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

伤害性信息通过。初级传入AS和C纤维到脊髓背角，特别是胶状质(SG)，在那里这种传递受到包括大麻素在内的各种内源性物质的调节。本研究项目考察了大麻素对兴奋性(谷氨酸能)和。抑制性的。应用盲目全细胞膜片钳技术对成年大鼠脊髓脑片SG神经元进行GABA能和甘氨酸能传递。结果表明：(1)内源性大麻素A-δ和C-纤维兴奋性突触后电流(EPSCs)分别被内源性大麻素花生酸甘油(2-AG；20μM)和大麻素受体激动剂Win 55,212-2(Win-2；5-10μM)抑制；(2)ANA(10μM)、2-AG(20μM)和Win-2(5μM)对单突触诱发的Aδ和C纤维兴奋性突触后电流(EPSC)的幅度均有抑制作用，前者的抑制程度大于后者；(3)ANA(10μM)、2-AG(20μM)和Win-2(5μM)对单突触诱发的A-…和C-纤维兴奋性突触后电流(EPSC)均有抑制作用(4)在1-5μM浓度范围内，ANA可降低电诱发的抑制性突触后电流(IPSCs)的幅度；(5)2-AG(20μM)和Win-2(5μM)；(6)ANA(10μM)的抑制作用可被大麻素受体拮抗剂SR141716A(5μM)分析；(7)ANA(10μM)可增加诱发的IPSC幅度的成对脉冲比率；(8)ANA(10μM)可降低自发IPSC的频率，但幅度不变。从外周以及GABA能和甘氨酸能抑制传递，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的表达，这些作用是由CBI受体介导的。提示这种Cb1受体的激活可能至少部分参与了鞘内给药所产生的抗伤害性感觉。较少

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