title: Volatile anesthetics excite mammalian nociceptor afferents recorded in vitro.
abstract: The present study investigated the actions of halothane, isoflurane, and enflurane on spontaneous discharge and evoked action potential activity in mammalian A-delta and C fiber nociceptors from the in vitro rabbit cornea. At 1 MAC halothane, isoflurane, and enflurane significantly (P less than 0.001) increased spontaneous discharge frequency of C fibers to 410%, 388%, and 569% of control, respectively. The anesthetics produced burst discharge activity over the concentration range of 0.25-1.5 MAC and depressed discharge activity at higher concentrations (greater than 3.0 MAC). Similar excitatory effects were produced by the potassium channel blocker 4-aminopyridine (250-500 microM). Variable effects on evoked discharge activity of A-delta fibers were observed. Halothane reduced action potential amplitude (77.3 +/- 4.5% of control +/- SD; n = 6 at 1 MAC) and increased spike latency (0.42 +/- 0.075 ms). In contrast, the ethers decreased both spike latency (isoflurane by 0.31 +/- 0.064 ms and enflurane by 0.35 +/- 0.058 ms) and action potential amplitude. Halothane and the ether anesthetics produced a common excitatory action on C fibers; however, the differential depressant effects on A-delta fibers suggest that different membrane mechanisms of action are involved.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, California 94305.
authors.forename: M B
authors.initials: MB
authors.lastname: MacIver
authors.forename: D L
authors.initials: DL
authors.lastname: Tanelian
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D003315:Cornea / Q000294:innervation; D004558:Electric Stimulation; D004737:Enflurane / Q000494:pharmacology; D005071:Evoked Potentials; D006221:Halothane / Q000494:pharmacology; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation; D011188:Potassium / Q000502:physiology; D011817:Rabbits
chemical_list: D000777:Anesthetics; D004737:Enflurane; D015761:4-Aminopyridine; D007530:Isoflurane; D011188:Potassium; D006221:Halothane