Site-Specific, Dose-Dependent, and Sex-Related Responses to the Experimental Pain Model Induced by Intradermal Injection of Capsaicin to the Foreheads and Forearms of Healthy Humans

Aims: To investigate whether trigeminal manifestations of pain, sensitization, and vasomotor responses following the intradermal injection of capsaicin to the foreheads differ from manifestations following injection of capsaicin in the forearms of healthy humans. Dose dependency and sex-related differences of the evoked responses were also studied. Methods: Twenty-eight healthy volunteers (14 women, 14 men) participated in 2 separate experiments: (1) Features of pain and vasomotor responses following intradermal injection of capsaicin (100 µg/100 µL) to the forehead and forearm were compared. (2) The features after intradermal injection of 2 different doses of capsaicin (50, 100 µg/100 µL) to the forehead were also studied. In both experiments the effect of sex was also investigated. Results: Experiment 1 showed that peak pain intensity (F [1,104] = 24.4, P .001) and duration (F [1,104] = 13.3, P .001) were greater in the forehead. However, the areas of visible flare (F [1,104] = 5.7, P .05) and secondary pinprick hyperalgesia (F [1,104] = 155.1, P .001) were significantly larger in the forearm. Experiment 2 indicated that peak pain intensity in the forehead was not affected by the capsaicin dose (F [1,52] = 1.6, P = .214), but duration of pain (F [1,52] = 6.0, P .05) and perceived pain area (F [1,52] = 13.5, P .001) were greater for the higher dose. The areas of visible flare (F [1,52] = 27.5, P .001) and secondary pinprick hyperalgesia (F [1,52] = 65.6, P .001) were also larger for the higher dose. In both experiments, women showed greater manifestations in several responses. Conclusion: Capsaicin-evoked sensory and vasomotor manifestations were different in the forehead and forearm. The differences are most likely due to the differences in innervation density and neurovascular activity. The capsaicin-induced effects were demonstrated to be dose-dependent and sex-related phenomena. Keywords: capsaicin, forearm, forehead, sex, trigeminal