Our aim is to investigate the role of nociceptive neurons in the peripheral and central nervous system in mediating cutaneous pain, itch and hyperalgesia. Peripheral neural mechanisms of chemogenic pain and itch will be studied by obtaining psychophysical measures in humans of the threshold, magnitude and duration of sensation during and after a superficial intradermal injection of capsaicin (pain) or histamine (itch). After injection of capsaicin, heat and mechanical stimuli will be applied directly to (or outside of) the injection site in order to determine the time course and magnitude of primary (and secondary) hyperalgesia. We will record, in the anesthetized monkey, the evoked responses in single A-fiber and C-fiber nociceptors when the same stimuli are applied within or near their cutaneous receptive fields. Results will determine the chemical sensitivity of nociceptors in relation to chemogenic pain, itch and hyperalgesia. The central neural contributions to heat pain, hyperalgesia after heat injury or intradermal injection of capsaicin, and itch after intradermal injection of histamine will be studied by recording evoked responses from single """"""""nociceptive specific"""""""" and """"""""wide dynamic range"""""""" neurons within the ventral posterior lateral thalamus in awake monkeys trained to escape or tolerate and detect heat stimuli used in the psychophysical experiments in humans. The results will be useful in identifying those central neurons, at the level of the thalamus, that process sensory information about pain, itch and hyperalgesia. Both the peripheral and central studies are prerequisites to developing specific pharmacologic agents that act peripherally to prevent endogenous chemicals from sensitizing nociceptors or act centrally to block sensory processing in nociceptive neurons.
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