Differential effects of experimental central sensitization on the time-course and magnitude of offset analgesia

Pain perception is temporally altered during states of chronic pain and acute central sensitization; however, the mechanisms contributing to temporal processing of nociceptive information remain poorly understood. Offset analgesia is a phenomenon that reflects the presence of temporal contrast mechanisms for nociceptive information and can provide an end point to study temporal aspects of pain processing. In order to investigate whether offset analgesia is disrupted during sensitized states, 23 healthy volunteers provided real-time continuous visual analogue scale responses to noxious heat stimuli that evoke offset analgesia. Responses to these stimuli were evaluated during capsaicin-heat sensitization (45°C stimulus, capsaicin cream 0.1%) and heat-only sensitization (40°C stimulus, placebo cream). Capsaicin-heat sensitization produced significantly larger regions of secondary mechanical allodynia compared to heat-only sensitization. Although areas of mechanical allodynia were positively related to individual differences in heat pain sensitivity, this relationship was altered at later time points after capsaicin-heat sensitization. Heat hyperalgesia was observed in the secondary region following both capsaicin-heat and heat-only sensitization. Increased latencies to maximal offset analgesia and prolonged aftersensations were observed only in the primary regions directly treated by capsaicin-heat or heat alone. However, contrary to the hypothesis that offset analgesia would be reduced following capsaicin-heat sensitization, the magnitude of offset analgesia remained remarkably intact after both capsaicin-heat and heat-only sensitization in zones of both primary and secondary mechanical allodynia. These data indicate that offset analgesia is a robust phenomenon and engages mechanisms that interact minimally with those supporting acute central sensitization.