Histopathological Changes of Streptozotocin-induced Painful Diabetes and Antihyperalgesic Effect of Capsaicin Cream in Rats

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To investigate the association between streptozotocin (STZ)-induced painful diabetic neuropathy and the antihyperalgesic effect of capsaicin cream in rats, we first examined the antihyperalgesic effect of capsaicin cream and subsequently performed peripheral neurohistochemical examinations of neuropathic rats. Mechanical hyperalgesia occurred 2 weeks after STZ injection and persisted for 8 weeks of testing. The neuropathy was alleviated by a single application of 0.1% capsaicin cream, but not by cream base. The hyperalgesia did not decrease when the capsaicin cream was applied to normal animals. On the other hand, for dorsal root ganglion (DRG) neurons and hind paw cutaneous nerves, the neurohistochemical examination showed no difference between STZ rats and control rats with capsaicin (vanilloid) receptor subtype 1 (VR1) and NF200 double immunohistochemical staining of DRG neurons, but an increase in A-fibers was seen in the hind paw cutaneous nerves of the STZ rats compared to the control rats. Neither STZ rats nor control rats were toxically affected by the single application of 0.1% capsaicin cream. These results suggest that a single application of capsaicin cream exerts an antihyperalgesic effect in rats with painful neuropathy and increases peripheral A-fibers. However, we could not clarify how VR1 was involved in the effect in rats with STZ painful diabetic neuropathy.