Central neuronal changes in recurrent visceral pain.

Repeated colics from urinary calculosis produce referred muscle hyperalgesia whose extent is proportional to the number of colics. The pathophysiology of this hyperalgesia was investigated in electrophysiological studies (spinal cord recordings) on an animal model of artificial ureteral calculosis. Stone-implanted rats show both visceral pain episodes and muscle hyperalgesia of the ipsilateral lumbar musculature; the extent of hyperalgesia is a function of the number of episodes. In the dorsal horn of stone-rats compared to controls the following were found: a) significantly higher percentages of neurons driven by stimulation of the hyperalgesic muscle, of spontaneously active cells with muscle input and of neurons with muscle input with a low mechanical threshold of activation, and b) a significantly higher frequency of background activity of spontaneously active cells with muscle input. These findings were proportional in extent to the number of visceral episodes presented by the rats before recordings; in cases of an extremely high number (> 50), several neurons also displayed abnormal activity, i.e. permanent short rhythmic bursts. These changes reflect a state of central sensitization and are probably due to the abnormal inflow from the affected ureter which facilitates the central effect of muscular input, thus accounting for the referred hyperalgesia. The degree of sensitization appears to be a function of the repetition of the visceral afferent barrage.