A pharmacological approach to elucidation of the role of different nerve fibres and receptor endings in mediation of pain.

Capsaicin, after initial stimulation, induced a long-lasting insensitivity to chemical pain stimuli without reducing the sensitivity to mechanical pain. The effect was peripheral as shown by recording action potentials from sensory nerves. In order to throw light on the receptors responsible for chemogenic pain, the specificity of the capsaicin effect was analysed. 1. In cats, capsaicin given in close arterial injection excited the slowest conducting C2 fibres as measured by the collision technique on the saphenous nerve. In rats, the frequency of action potentials evoked by s.c. injection of capsaicin was sensitized by rapid warming of the skin area, while sudden cooling had a blocking effect. On the human skin, the threshold of thermal pain was shifted from 45 degrees C to 30-31 degrees C; below this skin temperature, the burning pain and hyperalgesia induced by capsaicin treatment disappeared and cold sensation remained unimpaired. 2. On the human tongue, local capsaicin desensitization resulted in an elevated threshold of warm discrimination, while gustatory sensitivity as well as the capacity for discriminating cold or tactile stimuli remained unimpaired. 3. It is concluded that capsaicin is a selective sensory blocking agent which acts by stimulation and subsequent sensory blockage of polymodal nociceptors and warm receptors.