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Genetic variation in pain sensation and sensitivity to opioid

痛觉和阿片类药物敏感性的遗传变异

基本信息

批准号：
17390431
负责人：
KAWAMATA Mikito
金额：
$ 9.98万
依托单位：
Shinshu University (2007)Sapporo Medical University (2005-2006)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

项目摘要

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

在乌拉坦麻醉下，对小鼠的胶质神经元进行全细胞膜片钳记录。将无害性吹气刺激和用镊子进行的有害性捏刺激均施加到后爪上每个神经元的感受野。穿过视野中心的皮肤、筋膜和肌肉切开一个 5 毫米长的切口。用6-0尼龙缝合线将皮肤贴合。作为行为研究，CBA品系小鼠切开后自发性疼痛相关行为得分最高，A品系小鼠切开后自发疼痛相关行为得分最低。 A品系小鼠切开后自发性疼痛评分没有显着增加。评估了延髓头端腹内侧、RVM、神经元对mu激动剂DAMGO的影响。作为一项行为研究，长期植入脑室内导管。在脑室内注射 mu 受体激动剂 DAMGO 之前和之后测量了捏刺激的撤回潜伏期。 A 品系小鼠比 CBA 品系小鼠对 DAMGO 更敏感。在电生理实验中，将钨微电极从小脑表面推进到腹侧延髓400-500〓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 神经元根据其对有害刺激的反应被分为 ON、OFF 或 NEUTRAL 细胞。在脑室内注射 DAMGO 之前和之后记录神经元对 ON 和 OFF 细胞机械刺激（捏）的自发活动和诱发反应。 A品系小鼠的ON细胞比CBA品系小鼠更容易被DAMGO抑制。与 CBA 品系小鼠相比，DAMGO 更大程度地抑制了 A 品系小鼠因捏刺激而导致的放电率下降。因此，与 CBA 品系小鼠相比，A 品系小鼠的 ON 和 OFF 细胞对 mu 受体的激活更敏感。因此，参与疼痛处理的区域中的神经元和回路网络的反应特性是由基因决定的。反应特性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。较少的