Department of Physiology, Saga Medical School, Saga, Japan.
J Neurosci Res. 2012 Sep;90(9):1830-41. doi: 10.1002/jnr.23059. Epub 2012 Apr 10.
Although opioids inhibit action potential (AP) conduction in primary-afferent fibers, this has not yet been fully examined. We investigated by using the sharp glass microelectrode technique how opioids (morphine, codeine, and ethylmorphine) affect APs recorded from adult rat dorsal root ganglion (DRG) neurons in response to sciatic nerve stimulation. The DRG neurons were classified into three types, Aα/β, Aδ, and C, according to AP characteristics, including the fiber conduction velocity (CV) of the neuron. AP of the Aα/β neuron was reduced in peak amplitude by each of the opioids in a reversible and concentration-dependent manner. The potency sequence was ethylmorphine > codeine = morphine (IC(50) = 0.70, 2.5, and 2.9 mM, respectively), indicating that this AP inhibition is related to the chemical structure of the opioid. Each of the Aδ and C neuron APs was also inhibited by the opioids; ethylmorphine had a tendency to inhibit APs more effectively than codeine and morphine. This inhibition was variable in extent among neurons and was either comparable to or greater than that of the Aα/β neuron AP. The opioid-induced AP inhibitions were unaffected by nonspecific opioid-receptor antagonist naloxone; opioid-receptor agonists did not affect APs. In conclusion, the opioids inhibited APs in DRG neurons without opioid-receptor activation; this inhibition was different among neurons having different primary-afferent fiber CVs and also among the three kinds of opioid. The inhibition by opioid of primary-afferent fiber AP conduction is suggested to be distinct in extent among fibers conveying distinct types of nociceptive information.
虽然阿片类药物抑制初级传入纤维中的动作电位 (AP) 传导,但这尚未得到充分研究。我们使用尖锐玻璃微电极技术研究了阿片类药物(吗啡、可待因和乙基吗啡)如何影响从成年大鼠背根神经节 (DRG) 神经元记录的对坐骨神经刺激的反应中的 AP。根据 AP 特征,包括神经元的纤维传导速度 (CV),将 DRG 神经元分为三种类型,Aα/β、Aδ 和 C。Aα/β 神经元的 AP 峰值幅度被每种阿片类药物以可逆和浓度依赖性的方式降低。阿片类药物的效力顺序为乙基吗啡 > 可待因 = 吗啡(IC50 分别为 0.70、2.5 和 2.9 mM),表明这种 AP 抑制与阿片类药物的化学结构有关。Aδ 和 C 神经元的 AP 也被阿片类药物抑制;乙基吗啡比可待因和吗啡更倾向于有效抑制 AP。这种抑制在神经元之间的程度上是可变的,并且与 Aα/β 神经元 AP 的抑制程度相当或更大。非特异性阿片受体拮抗剂纳洛酮对阿片类药物诱导的 AP 抑制没有影响;阿片受体激动剂对 AP 没有影响。总之,阿片类药物抑制 DRG 神经元中的 AP,而不激活阿片受体;这种抑制在具有不同初级传入纤维 CV 的神经元之间以及三种阿片类药物之间是不同的。阿片类药物对初级传入纤维 AP 传导的抑制在程度上被认为在传递不同类型伤害性信息的纤维之间是不同的。