Dose-dependent pain and mechanical hyperalgesia in humans after intradermal injection of capsaicin

Psychophysical measurements of pain and mechanical hyperalgesia were obtained following different doses of capsaicin injected intradermally into the forearms of human subjects. Each subject received a 10 μ1 injection of the vehicle and capsaicin doses of 0.01, 0.1, 1, 10 and 100μg. The relationship between capsaicin dose and the magnitude and duration of pain was determined using the method of magnitude estimation. In addition to pain, capsaicin produced a flare and mechanical hyperalgesia. The area of flare and the area and time course of mechanical hyperalgesia were measured as a function of the dose of capsaicin. The magnitude and duration of pain, based on averaged responses of all subjects, increased as a negatively accelerating function of dose. The lowest dose of capsaicin to produce more pain than the vehicle was 0.1 μg. The area and duration of mechanical hyperalgesia also increased as a negatively accelerating function of dose. The lowest dose of capsaicin to produce an area of mechanical hyperalgesia was 0.1μg. An area of hyperalgesia was present within seconds following injection. For doses of 10 and 100 μg, the area of hyperalgesia grew to reach a maximum within 5 and 7 min following the injection and gradually decreased, disappearing within 15 and 137 min, respectively. Capsaicin doses of 1, 10 and 100μg produced successively greater areas of flare. The results demonstrate that humans can scale the magnitude of pain produced by capsaicin in a dose-dependent fashion. Further, the duration of pain, the area and duration of mechanical hyperalgesia, and the area of flare are dose-dependent. It is concluded that intradermal injection of capsaicin will provide a useful method of carrying out parallel psychophysical and neurophysiological studies of pain and hyperalgesia.