Study on a relationship between dopamine in the substantia nigra and pain system

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To investigate the role of mesostriatal dopamine system in pain processing, we examined the withdrawal response of rat hindpaws to mechanical stimulus at 1, 4, and 12 weeks after unilateral 6-hydroxydopamine (6-HODA) lesions of the mesostriatal pathway. In all of the 6-OHDA rats examined, almost no tyrosine hydroxylase (TH) immunoreactivity was detected in the substantia nigra, ventral tegemental area, and striatum ipsilateral to 6-OHDA lesions. Alteration in the withdrawal response in this model animal was evaluated by comparing the latency of withdrawal reflex following the mechanical stimulus to the hindpaw. The latency of withdrawal response in the 6-OHDA rats was significantly reduced in the side ipsilateral to 6-OHDA lesions at all times observed, whereas that was not changed through the period observed in the contralateral side, indicating that dopamine depletion in the mesostriatal system has the influence on withdrawal response to the mechanical stimulus. These results show that the unilateral dopamine depletion causes hypersensitivity to the mechanical stumulus in the ipsilateral side, suggesting that, at least in part, dopamine in the mesostriatal system may be involved in sensory processing including pain sensation induced by mechanical stimulation.To clarify whether the hypersensitivity to mechanical stimulation in the 6-OHDA rats is derived from pain processing at the spinal cord level, Fos expression in the dorsal horn was examined following noxious mechanical stimulation to the hindpaws of this model animal. As compared with the number of Fos-positive neurons in the dorsal horn following noxious stimulation to the hindpaw of the ipsilateral and contralateral sides, there was no cleare difference in the number of Fos-positive neurons, suggesting that hypersensitivity to mechanical stimulation in 6-OHDA rats may not be caused in the spinal level.