Direct GABAergic and glycinergic inhibition of the substantia gelatinosa from the rostral ventromedial medulla revealed by in vivo patch-clamp analysis in rats
Direct GABAergic and glycinergic inhibition of the substantia gelatinosa from the rostral ventromedial medulla revealed by in vivo patch-clamp analysis in rats
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DOI：
10.1523/jneurosci.4856-05.2006
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发表时间：
2006-02-08
影响因子：
5.3
通讯作者：
Yoshimura, M
中科院分区：
文献类型：
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作者：
Kato, G;Yasaka, T;Yoshimura, M
刺激吻侧腹内侧髓质（RVM）被认为通过激活下行至脊髓背角的血清素能系统来发挥镇痛作用；然而，伤害传递是如何被下行系统调节的还没有完全阐明。为了研究RVM的抑制机制，采用体内膜片钳技术记录成年大鼠脊髓明胶质（SG）在化学（谷氨酸注射）和电刺激（ES）下产生的IPSCs。在电压箝位模式下，RVM谷氨酸注射剂和RVM- es在SG神经元中产生的IPSCs的频率和幅度均增加，且未被谷氨酸受体拮抗剂阻断。5 -羟色胺受体拮抗剂出人意料地没有效果，但GABA(a)受体拮抗剂双库兰或甘氨酸受体拮抗剂士的宁完全抑制了RVM刺激诱导的IPSCs的增加。RVM- es诱导的IPSCs在传导速度为3.1-20.7 m/s的20 Hz刺激下表现出固定的潜伏期和无失效，表明单突触gaba能和/或甘氨酸能输入通过髓鞘纤维从RVM下降到SG。在电流箝位模式下，施加于同侧后肢感受野的有害机械刺激引发的动作电位被RVM-ES抑制的神经元超过一半（63%；16个中的10个）。这些发现表明，rvm介导的对SG有害输入的抗伤害性作用可能优先通过直接的氨基丁酸能和甘氨酸能途径发挥作用。
Stimulation of the rostral ventromedial medulla (RVM) is believed to exert analgesic effects through the activation of the serotonergic system descending to the spinal dorsal horn; however, how nociceptive transmission is modulated by the descending system has not been fully clarified. To investigate the inhibitory mechanisms affected by the RVM, an in vivo patch-clamp technique was used to record IPSCs from the substantia gelatinosa (SG) of the spinal cord evoked by chemical ( glutamate injection) and electrical stimulation (ES) of the RVM in adult rats. In the voltage-clamp mode, the RVM glutamate injection and RVM-ES produced an increase in both the frequency and amplitude of IPSCs in SG neurons that was not blocked by glutamate receptor antagonists. Serotonin receptor antagonists were unexpectedly without effect, but a GABA(A) receptor antagonist, bicuculline, or a glycine receptor antagonist, strychnine, completely suppressed the RVM stimulation-induced increase in IPSCs. The RVM-ES-evoked IPSCs showed fixed latency and no failure at 20 Hz stimuli with a conduction velocity of >3 m/s (3.1-20.7 m/s), suggesting descending monosynaptic GABAergic and/or glycinergic inputs from the RVM to the SG through myelinated fibers. In the current-clamp mode, action potentials elicited by noxious mechanical stimuli applied to the receptive field of the ipsilateral hindlimb were suppressed by the RVM-ES in more than half of the neurons tested (63%; 10 of 16). These findings suggest that the RVM-mediated antinociceptive effects on noxious inputs to the SG may be exerted preferentially by the direct GABAergic and glycinergic pathways to the SG.