Secondary heat hyperalgesia induced by melittin in humans

Melittin, which is a principal protein of honeybee venom, can induce mechanical hyperalgesia in humans. The characteristics of the melittin induced mechanical hyperalgesia are quantitatively and qualitatively different from those evoked by capsaicin. The aim of the present study was to investigate in detail secondary heat hyperalgesia induced by melittin in humans. In six healthy volunteers, 10 μg of melittin was injected intradermally on the volar forearm, and VAS score to radiant heat stimuli (focused light from a xenon lamp) was assessed around the injection site 5, 30, and 60 min after injection. For normalization purposes, a pain rating index was calculated as the individual heat evoked VAS scores obtained after melittin divided by the individual baseline VAS scores. A two-way ANOVA revealed a significant increase of the pain rating index over time (F = 3.6; P = 0.03). The pain rating index at 60 min was significantly larger than at 5 min (P = 0.04) and at 30 min (P = 0.03). These results demonstrated slowly developing secondary heat hyperalgesia after injection of melittin. A possible contribution of peripheral inflammatory responses to the manifestation of secondary heat hyperalgesia is suggested, which in reality render the distinction between the primary and secondary area of heat hyperalgesia unnecessary.