Non-noxious A fiber afferent input enhances capsaicin-induced mechanical hyperalgesia in the rat

Intradermal injection of capsaicin induces primary hyperalgesia at the injection site and secondary hyperalgesia in the surrounding undamaged skin. The secondary hyperalgesia is thought to be due to central sensitization of the dorsal horn neurons while primary hyperalgesia is caused by sensitization of nociceptors in the damaged skin. In this study, we asked if additional non-noxious afferent input from the undamaged skin influences the already developed secondary hyperalgesia, which follows an intradermal injection of capsaicin. Capsaicin dissolved in olive oil was injected into the middle of the hind paw of male Sprague-Dawley rats (250-300 g) under gaseous anesthesia. This produced a decrease in the mechanical threshold at the base of the toes for hind limb withdrawals lasting for 1-2 h, thus showing a short-lasting (hours) secondary hyperalgesia. When the capsaicin injection was immediately followed by repeated non-noxious mechanical stimuli or weak electrical stimuli (A fiber strength) applied to the area of secondary hyperalgesia (toes) for 30 min, the reduction of the mechanical threshold lasted longer than 24 h. These results suggest that non-noxious A fiber afferent input can powerfully modulate central sensitization in the spinal dorsal horn, causing the duration of the secondary hyperalgesia to be greatly extended.