Genetic variation in pain sensation and sensitivity to opioid

用全细胞膜片钳对氨基甲酸乙酯麻醉小鼠明胶质神经元进行记录。对后爪各神经元的感受野分别施加非有害的吹气刺激和有害的钳捏刺激。在野中心的皮肤、筋膜和肌肉处做一个5 mm长的切口。皮肤用6-0尼龙缝线缝合。作为行为学研究，CBA品系小鼠切口后自发性疼痛相关行为得分最高，a品系小鼠切口后自发性疼痛相关行为得分最低。A品系小鼠切口后自发性疼痛评分无明显升高。观察延髓吻侧腹内侧、RVM、神经元对mu激动剂DAMGO的反应。作为一项行为学研究，长期植入脑室内导管。在脑室内注射mu受体激动剂DAMGO前后测量捏刺激的戒断潜伏期。与CBA系小鼠相比，更多的小鼠对DAMGO更敏感。在电生理实验中，钨微电极从小脑表面进入延髓腹侧，深度为400-500 μ m，直到单个RVM神经元的动作电位可以在细胞外分离。RVM神经元根据其对有害刺激的反应分为开、关或中性细胞。记录脑室内注射DAMGO前后神经元对ON和OFF细胞机械刺激（捏压）的自发活动和诱发反应。DAMGO对A系小鼠ON细胞的抑制作用明显优于CBA系小鼠。与CBA小鼠相比，DAMGO对A品系小鼠扣压刺激下的放电率下降有更大的抑制作用。因此，A品系小鼠的ON和OFF细胞对mu受体的激活比CBA品系小鼠更敏感。因此，参与疼痛处理区域的神经元和回路网络的反应特性是由基因决定的。反应性质的差异可能是人类疼痛敏感性和镇痛药敏感性变化的机制之一。少

Whole-cell patch clamp recordings were made from substantia gelatinosa neurons in mice under anesthesia with urethane. Both non-noxious air puff stimuli and noxious pinch stimuli with forceps were applied to the receptive field of each neuron on the hindpaw. A 5-mm-long incision was made through the skin, fascia and muscle of the center of the field. The skin was apposed with a 6-0 nylon suture. As a behavioral study, the highest score of spontaneous pain-related behavior was seen in CBA strain mice after incision, and the lowest score of the behavior was seen in A strain mice after incision. The spontaneous pain scores did not significantly increase in A strain mice after incision.Rostral ventromedial medulla, RVM, neurons to mu agonist DAMGO was evaluated. As a behavioral study, an intracerebroventricular catheter was chronically implanted. The withdrawal latency to pinch stimuli was measured before and after intracerebroventricular injection of the mu receptor agonist DAMGO. A strai … More n mice were more sensitive to DAMGO than were CBA strain mice. In electrophysiological experiments, a tungsten microelectrode was advanced from the surface of the cerebellum into the ventral medulla to a depth of 400-500 〓m until action potentials from a single RVM neuron could be extracellularly isolated. An RVM neuron was classified as an ON, OFF or NEUTRAL cell by its responses to application of noxious stimuli. Spontaneous activity and evoked responses of the neurons to mechanical stimuli (pinch) of ON and OFF cells were recorded before and after intracerebroventricular injection of DAMGO. ON cells in A strain mice were more easily suppressed by application of DAMGO than in CBA strain mice. DAMGO more greatly suppressed the decrease in firing rates by pinch stimuli in A strain mice than were those in CBA strain mice. Thus, both ON and OFF cells in A strain mice were more sensitive to activation of mu receptors than were those in CBA strain mice.Thus, response properties of neurons and networks of circuits in regions that are involved in pain processing are genetically determined. The difference in the response properties may be one of the mechanisms of variation in pain sensitivity and sensitivity to analgesics in humans. Less