Halothane sensitizes cutaneous nociceptors in monkeys

1. The effects of halothane on the responses of C-fiber (CMHs) and A-fiber (AMHs) nociceptive afferents sensitive to mechanical and heat stimuli were studied in monkeys. The response to heat stimuli was studied with use of a laser thermal stimulator that provided stepped increases in skin temperature over a 7.5-mm-diameter area with rise times to the desired temperature near 100 ms. Recordings were obtained from single fibers that innervated the glabrous skin of the hand using a teased-fiber dissection technique. 2. In initial studies the response of 32 CMHs and 45 AMHs in monkeys anesthetized with pentobarbital sodium (3-6 mg·kg^-1·h^-1) was compared with the response of 12 CMHs and 23 AMHs in monkeys anesthetized with a combination of halothane (0.8%) and N₂O (67%). A standardized set of 10 3-s heat stimuli ranging from 41 to 49°C delivered every 30 s were applied to the receptive field. Both AMHs and CMHs had a lower threshold and greater response to suprathreshold heat stimuli under conditions of halothane-N₂O anesthesia. The threshold to mechanical stimuli, as tested by von Frey hairs, was not significantly different. 3. Five CMHs and 5 AMHs were studied in a crossover study in which responses to the 41-49°C stimuli were obtained first under halothane-N₂O (0.8%-67%) anesthesia, then under an ultrashort acting barbiturate, methohexital (2-9 mg/kg) over 15 min), and finally once again under halothane-N₂O anesthesia. For the five CMHs, the mean cumulative response was 1.8 times greater, whereas for the five AMHs the response was 4.7 times greater under halothane as opposed to barbiturate anesthesia. 4. The response of five CMHs from monkeys anesthetized with a constant infusion of pentobarbital sodium (3-6 mg·kg^-1·^-1) increased markedly when halothane (up to 3%) was added. This increase was dose dependent and reversible. To exclude the possibility that barbiturates and halothane had confounding interactive effects, three CMHs and two AMHs were studied in monkeys rendered brain dead, thus allowing recordings to be made without use of a base-line anesthetic. Once again, halothane induced a substantial increase in response. Methohexital did not decrease the response of five other CMHs in monkeys anesthetized with halothane-N₂O. 5. The effects of halothane did not relate to effects on sympathetic tone, blood pressure, or cutaneous perfusion. The effect of halothane was still present when sympathetic supply to the extremity was interrupted by sectioning the brachial plexus or by applying local anesthetic to the nerve proximal to the recording site. The halothane increased the response of CMHs even when the anesthetic's hypotensive effect was blocked by phenylephrine. Changes in skin perfusion as determined from measurements of skin temperature did not account for the effects of halothane. End-tidal CO₂ and core temperature were maintained at physiological levels (P(CO₂) at 32-40 Torr, core temperature near 28°C) during all experiments, and thus fluctuation of these parameters could not be the basis for the effects of halothane. 6. Halothane sensitizes nociceptors to heat stimuli in a reversible dose-dependent manner. This effect is independent of effects on sympathetic tone and perfusion. It is likely that the effects of halothane are the result of direct effects on the cutaneous receptor.