Capsaicin Responses in Heat-Sensitive and Heat-Insensitive A-Fiber Nociceptors

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Abstract
The recently cloned vanilloid receptor (VR1) is postulated to account for heat and capsaicin sensitivity in unmyelinated afferents. We sought to determine whether heat and capsaicin sensitivity also coexist in myelinated nociceptive afferents. Action potential (AP) activity was recorded from single A-fiber nociceptors that innervated the hairy skin in monkey. Before intradermal injection of capsaicin (10 μg/10 μl) into the receptive field, nociceptors were classified as heat-sensitive (threshold, ≤53°C, 1 sec) or heat-insensitive afferents and as mechanically sensitive (von Frey threshold, n = 16) were insensitive to mechanical stimuli but responded to the intradermal injection of capsaicin (69 ± 7 APs in 10 min). Responsiveness to mechanical stimuli, thermal stimuli, and capsaicin varied in their receptive fields; the majority of receptive field sites (24 of 36) were responsive to only one or two stimulus modalities, whereas only eight sites responded to all three modalities. For most heat-insensitive afferents, the activity induced by the capsaicin injection did not exceed the activity induced by needle insertion alone. However, the largest response to capsaicin (314 ± 98 APs in 10 min) was observed for five afferents that were insensitive to heat as well as mechanical stimuli and therefore may be classified as cutaneous chemoreceptors. These results suggest that A-fiber nociceptors play a role in the pain and hyperalgesia associated with capsaicin injection. Our finding that a subgroup of capsaicin-sensitive A-fiber nociceptors are insensitive to heat predicts the existence of heat-insensitive capsaicin receptors.