Genetic variation in pain sensation and sensitivity to opioid

在乌拉坦麻醉下，对小鼠胶状质神经元进行全细胞膜片钳记录。非伤害性的空气喷刺激和伤害性的钳子捏刺激施加到后爪上的每个神经元的感受野。在视野中心的皮肤、筋膜和肌肉上做一个5 mm长的切口。用6-0尼龙缝线对合皮肤。在行为学方面，CBA品系小鼠切口后自发痛行为评分最高，A品系小鼠切口后自发痛行为评分最低。A系小鼠切开后自发痛评分无明显增加，取延髓头端腹内侧区（RVM）神经元，测定其对μ受体激动剂DAMGO的敏感性。作为一项行为研究，长期植入脑室导管。在侧脑室注射μ受体激动剂DAMGO之前和之后测量对捏刺激的退缩潜伏期。一条海峡 ...更多信息 n小鼠对DAMGO的敏感性高于CBA品系小鼠。在电生理学实验中，将钨微电极从小脑表面推进到延髓腹侧400-500 μ m的深度，直到可以在细胞外分离出单个RVM神经元的动作电位。RVM神经元根据其对伤害性刺激的反应分为ON、OFF或NEUTRAL细胞。记录侧脑室注射DAMGO前后ON和OFF细胞的自发活动和对机械刺激（捏）的诱发反应。应用DAMGO比CBA品系小鼠更容易抑制A品系小鼠中的ON细胞。与CBA品系小鼠相比，DAMGO更大程度地抑制A品系小鼠因捏夹刺激而导致的放电率下降。因此，A系小鼠的ON和OFF细胞对mu受体的激活比CBA系小鼠更敏感，因此，参与疼痛处理的区域的神经元和回路网络的响应特性由遗传决定。反应特性的差异可能是人类疼痛敏感性和对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