Phaimacological analysis of a novel NMDA receptor mediating synaptic responses involued in pain transmossion in the spinal cord

外周有害信息被认为是通过未myclinated的c -和薄髓鞘的adela传入神经传递到浅表背角，特别是脊髓中的明胶质（SG， Rexed的II层）神经元，在那里疼痛传递被调节。我们研究了急性或慢性疼痛刺激对谷氨酸能兴奋性突触传递的影响，采用盲全细胞膜片钳技术对成年大鼠脊髓背根连接的SG神经元进行了研究。通过重复刺激阿德尔塔传入事件，SG神经元不仅表现出非NMDA反应，而且表现出NMDA反应；后者对AP-5或Mg^2^+的敏感性低于其他中枢神经元(1)。辣椒素通过刺激C-而不是阿德尔塔传入纤维，在超过30分钟的时间内减弱SG神经元的兴奋性突触后电流的振幅，从而增强自发递质释放(2)。足底注射完全弗氏佐剂引起炎症的大鼠SG神经元表现出与幼稚大鼠不同的突触传递。在炎症大鼠中，接受β传入输入的SG神经元数量减少，而接受a43传入输入的SG神经元数量增加(3)。这些结果表明，SG神经元中的谷氨酸能传递是由非NMDA和NMDA受体介导的，并且这些受体在疼痛刺激后表现出可塑性改变。例如，辣椒素专门作用于c -纤维，导致诱发传递的抑制；这至少在一定程度上解释了辣椒素的止痛作用。外周炎症诱导从深层椎板到SG的β传入神经的重组；这可能在一定程度上促进了异位性疼痛的发展。

It is thought that peripheral noxious information is transmitted through unmyclinated C-and thinly-myelinated Adelta-afferents to superficial dorsal horn, particularly substantia gelatinosa (SG, lamina II of Rexed) neurons, in the spinal cord, where the pain transmission is modulated. We examined what effects acutely or chronically pain-eliciting stimuli have on glutamatergic excitatory synaptic transmission by applying the blind whole-cell patch-clamp technique to SG neurons of an adult rat spinal cord slice to which the dorsal root is attached. The SG neurons exhibited not only a non-NMDA but also NMDA response by stimulating repetitively Adelta-afferents ; the latter of which is less sensitive to AP-5 or Mg^2^+ than reported in other central neurons (1). Capsaicin potentiated spontaneous transmitter release (2) while attenuating the amplitude of excitatory postsynaptic currents evoked in SG neurons by stimulating C-, but not Adelta-afferent fibers, for more than 30 min. SG neurons in rats inflamed by an intraplantar injection of complete Freund's adjuvant displayed synaptic transmissions different from those in naive rats. In inflamed rats, SG neurons receiving Abeta-afferent inputs decreased in number whereas those having A43-afferent inputs increased (3). These results demonstrate that glutamatergic transmissions in SG neurons are mediated by both non-NMDA and NMDA receptors and that these exhibit a plastic alteration following a pain stimulation. For example, capsaicin acts on specifically C-fibers, resulting in an inhibition of evoked transmission ; this would account for, at least in part, an analgesic action of capsaicin. Peripheral inflammation induces a reorganization of Abeta-afferents to the SG from deeper laminae ; this may partly contribute to the development of allodynia.