Genetic variation in pain sensation and sensitivity to opioid

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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