To investigate the possible mechanisms involved in the alterations in sensitivity to pain in diabetic rats, we examined the influence of diabetes induced by streptozotocin (STZ) on the functions of the neuronal systems that contain substance P (SP) within the spinal cord. The threshold for pain perception as determined by a tail-pinch test was significantly reduced in diabetic rats. The levels of SP in the spinal cord from diabetic rats (116.9 +/- 16.3 pmol/g tissue) were significantly lower than those from the control rats (190.2 +/- 14.1 pmol/g tissue). Diabetic rats were found to have a significant increase in the number of binding sites for SP in dorsal spinal cord. The concentrations of binding sites in diabetic rats and in control rats were 102.1 +/- 17.3 fmol/mg protein and 52.6 +/- 6.6 fmol/mg protein, respectively. These data indicate that STZ-induced diabetic rats exhibit supersensitivity to SP in the spinal cord. This may be correlated, in part, with the reduction in the threshold for perception of pain in diabetic animals.