Chemosensitivity and sensitization of nociceptive afferents that innervate the hairy skin of monkey.

1. A large proportion of the cutaneous nociceptor population in monkey either does not respond to mechanical stimuli or has very high mechanical thresholds (> 6 bar). The goal of this study was to determine whether these mechanically insensitive nociceptive afferents (MIAs) differ from mechanically sensitive nociceptive afferents (MSAs) with regard to responses to chemical stimuli. 2. Teased-fiber techniques were used to record from 28 A delta-fiber (16 MIAs and 12 MSAs) and 23 C-fiber (10 MIAs and 13 MSAs) nociceptors in hairy skin of pentobarbital sodium-anesthetized monkeys. An electrocutaneous search technique was used to locate the putative receptive fields of the MIAs. The response to mechanical and heat stimuli was determined before and after intradermal injection of a standard mixture of algesic/inflammatory mediators (bradykinin, histamine, serotonin, and prostaglandin E1). 3. All 25 MSAs, but only 65% of the MIAs, responded to the chemical stimulus. The A delta-fibers, both MSAs and responsive MIAs, and the responsive C-fiber MIAs gave a robust discharge. In contrast, the C-fiber MSAs (the conventional polymodal C-fiber nociceptors) exhibited a significantly weaker response. Three MIAs responded only to the chemical mixture and not to mechanical or heat stimuli. 4. Before injection of the chemical mixture, a significantly smaller proportion of C-fiber MIAs (50%) than of C-fiber MSAs (92%) responded to heat stimuli, whereas a similar proportion (38%) of A delta-fiber MIAs and MSAs were heat sensitive. 5. Approximately one-half of the MIAs and MSAs were sensitized to mechanical stimuli after the chemical injection, as manifest by a decreased threshold and/or an enlarged receptive field. 6. The chemical injection sensitized 90% of A delta-fiber MSAs, but only 8% of A delta-fiber MIAs, to heat stimuli. In contrast, 38% of C-fibers were sensitized. 7. In 14 fibers, the chemical stimulus resulted in sensitization to mechanical stimuli without sensitization to heat stimuli, or vice versa. This dissociated sensitized state suggests that the molecular mechanisms of sensitization to heat and mechanical stimuli differ. 8. In conclusion, a large proportion of primate cutaneous nociceptors respond to intradermal injection of algesic/inflammatory mediators and may also become sensitized to mechanical and/or heat stimuli.