Lowered response threshold and increased responsiveness to mechanical stimulation of cutaneous nociceptive fibers in streptozotocin-diabetic rat skin in vitro--correlates of mechanical allodynia and hyperalgesia observed in the early stage of diabetes.

Rats rendered diabetic by streptozotocin (STZ) show allodynia and hyperalgesia and thus, have been offered as a model of pain in diabetic neuropathy. However, recent electrophysiological studies on these rats found that C-fiber nociceptors were not consistently hyperexcitable to mechanical stimulations by von Frey hairs and that there was no change in their response thresholds. In the present study, we used rat skin-saphenous nerve in vitro preparations, in which the receptive fields of identified single C-polymodal receptors (CPRs) can be accurately stimulated with a servo-controlled mechanical stimulator. Single fiber recordings from CPRs were performed in diabetic rats with an increased behavioral nociceptive response 7-19 days after STZ injection. The proportion of units with spontaneous activity and the magnitude of this activity increased in the diabetic preparations. The response thresholds of CPRs were significantly decreased with ramp-pressure stimulation and their response magnitude to the suprathreshold stimulation was significantly increased in diabetic rats. In addition, the response pattern to mechanical stimulation was also changed to a non-adapting type. These findings suggest that changes in CPRs contribute to the enhanced nociception observed in the early stage of diabetic neuropathy.