Secondary hyperalgesia and perceptual wind-up following intradermal injection of capsaicin in humans

Wind-up and secondary hyperalgesia both are related to central sensitization, but whereas the former is explained by homosynaptic facilitation, the latter is due to heterosynaptic facilitation. To investigate possible interactions between both types of facilitation, we tested for alterations of perceptual wind-up in the secondary hyperalgesic skin zone adjacent to a capsaicin injection with light touch (by a cotton wisp) and punctate stimuli (calibrated von Frey hairs and pin pricks). Temporal summation of pain sensation (perceptual wind-up) was only observed with a clearly noxious stimulus (pin prick) presented at a repetition frequency of 0.6 s−1, but not 0.2 s−1. Pain ratings to trains of pin pricks reached a plateau after 3–4 repetitions, which was 1.65 times the initial rating (‘wind-up ratio’). Injection of capsaicin induced a tenderness to mechanical stimuli in adjacent uninjured skin (secondary hyperalgesia), including hyperalgesia to light touch (allodynia) and hyperalgesia to punctate stimuli. Hyperalgesia to punctate stimuli was characterized by a leftward shift of the stimulus response function, corresponding to a decrease in pain threshold and an increase of painfulness of suprathreshold stimuli by a factor of 3–4. After capsaicin, the difference between the ratings of the first and last stimuli of trains of pin pricks was increased, but the ratio was unchanged. This behavior is equivalent to an increase in effective stimulus intensity, and could be mimicked by increasing the pin prick force from 20 mN to 40 and 80 mN in normal skin. Thus, the leftward shift of the stimulus response function fully accounts for all alterations of pain sensitivity to punctate stimuli in the zone of secondary hyperalgesia. We conclude that when the gain of spinal transmission was changed in secondary hyperalgesia, the gain of wind-up remained unchanged. These findings indicate that secondary hyperalgesia (heterotopic facilitation) and wind-up of pain sensation (homotopic facilitation) are independent phenomena.