The Mu Opioid Receptor Modulates Neurotransmission in the Rat Spinal Ventral Horn
The Mu Opioid Receptor Modulates Neurotransmission in the Rat Spinal Ventral Horn
复制标题
DOI：
10.1213/ane.0b013e318259393d
复制
发表时间：
2012-09-01
影响因子：
5.7
通讯作者：
Kohno, Tatsuro
中科院分区：
文献类型：
--
作者：
Honda, Hiroyuki;Kawasaki, Yasuhiko;Kohno, Tatsuro
背景：阿片类药物通过μ阿片受体抑制兴奋性神经传递并产生抗伤害作用。虽然MORs在脊髓腹角表达，但其功能和作用在很大程度上是未知的。方法：采用全细胞膜片钳技术，观察选择性μ阿片受体激动剂[D-Ala（2），-N-Me-Phe（4），Gly（5）-ol]Jenkephalin（DAMGO）对新生大鼠脊髓IX层神经元突触传递的影响。DAMGO产生外向电流在56%的第IX层神经元记录，与50%的有效浓度为0.1 μ M。电流-电压关系的分析揭示了约-86 mV的反转电位。这些电流不被河豚毒素阻断，但被Ba 2+或选择性μ拮抗剂抑制。此外，通过向移液管溶液中加入Cs+和四乙基铵或鸟苷5 '-[beta-thi]二磷酸三锂盐来抑制电流。此外，DAMGO降低自发兴奋性和抑制性突触后电流的频率，这些影响是不变的治疗与tetrodotoxin.CONCLUSION：我们的研究结果表明，DAMGO超极化脊髓第九层神经元G蛋白介导的激活K+通道激活后MORs。此外，突触前末梢上MORs的激活减少兴奋性和抑制性递质的释放。虽然传统上阿片类药物不被认为会影响运动功能，本研究记录了μ阿片类药物在脊髓第九层神经元中的神经调节作用，表明MORs可以影响运动活动。（Anesth Analg 2012;115：703-12）
BACKGROUND: Opioids inhibit excitatory neurotransmission and produce antinociception through mu opioid receptors (MORs). Although MORs are expressed in the spinal ventral horn, their functions and effects are largely unknown. Therefore, we examined the neuromodulatory effects of mu opioids in spinal lamina IX neurons at the cellular level.METHODS: The effects of the selective mu agonist [D-Ala(2),-N-Me-Phe(4), Gly(5)-ol]Jenkephalin (DAMGO) on synaptic transmission were examined in spinal lamina IX neurons of neonatal rats using the whole-cell patch-clamp technique.RESULTS: DAMGO produced outward currents in 56% of the lamina IX neurons recorded, with a 50% effective concentration of 0.1 mu M. Analysis of the current-voltage relationship revealed a reversal potential of approximately -86 mV. These currents were not blocked by tetrodotoxin but were inhibited by Ba2+ or a selective mu antagonist. Moreover, the currents were suppressed by the addition of Cs+ and tetraethylammonium or guanosine 5'-[beta-thi]diphosphate trilithium salt to the pipette solution. In addition, DAMGO decreased the frequency of spontaneous excitatory and inhibitory postsynaptic currents, and these effects were unaltered by treatment with tetrodotoxin.CONCLUSION: Our results suggest that DAMGO hyperpolarizes spinal lamina IX neurons by G protein-mediated activation of K+ channels after activation of MORs. Furthermore, activation of MORs on presynaptic terminals reduces both excitatory and inhibitory transmitter release. Although traditionally opioids are not thought to affect motor function, the present study documents neuromodulatory effects of mu opioids in spinal lamina IX neurons, suggesting that MORs can influence motor activity. (Anesth Analg 2012;115:703-12)