title: The effects of aromatic anesthetics on dorsal horn neuronal responses to noxious stimulation.
abstract: BACKGROUND
  Gamma-aminobutyric acid type A receptor potentiation and/or N-methyl-d-aspartate (NMDA) receptor inhibition might explain the anesthetic properties of fluorinated aromatic compounds. We hypothesized that depression of dorsal horn neuronal responses to noxious stimulation would correlate with the magnitude of effect of benzene (BNZ), o-difluorobenzene, and hexafluorobenzene (HFB) on NMDA receptors.
  
  
  METHODS
  Rats were anesthetized with desflurane. A T13-L1 laminectomy allowed extracellular recording of neuronal activity from the lumbar spinal cord. After discontinuing desflurane administration, MAC for each aromatic anesthetic was determined. A 5-s noxious mechanical stimulus was then applied to the hindpaw receptive field of nociceptive dorsal horn neurons, and single-neuron responses were recorded at 0.8 and 1.2 MAC. These responses were also recorded in decerebrate rats receiving BNZ and HFB at 0-1.2 MAC.
  
  
  RESULTS
  In intact rats, depression of responses of dorsal horn neurons to noxious stimulation by peri-MAC increases in BZN, o-difluorobenzene, and HFB correlated directly with their in vitro capacity to block NMDA receptors. In decerebrate rats, 1.2 MAC BNZ depressed nociceptive responses by 60%, with a further percentage decrease continuing from 0.8 to 1.2 MAC approximately equal to that found in intact rats. In decerebrate rats, HFB caused a progressive dose-related decrease in MAC (maximum 25%), but in intact rats, an increase from 0.8 to 1.2 neuronal response caused an (insignificant) increase in neuronal response.
  
  
  CONCLUSIONS
  The findings in intact rats suggest that NMDA blockade contributes to the depression of dorsal horn neurons to nociceptive stimulation by fluorinated aromatic anesthetics. These results, combined with the additional findings in decerebrate rats, suggest that supraspinal effects (perhaps on gamma-aminobutyric acid type A receptors) may have a supraspinal facilitatory effect on nociception for HFB.
authors.affiliation: Department of Anesthesiology and Pain Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Aubrey
authors.initials: A
authors.lastname: Yao
authors.forename: JongBun
authors.initials: J
authors.lastname: Kim
authors.forename: Richard
authors.initials: R
authors.lastname: Atherley
authors.forename: Steven L
authors.initials: SL
authors.lastname: Jinks
authors.forename: Earl
authors.initials: E
authors.lastname: Carstens
authors.forename: Sean
authors.initials: S
authors.lastname: Shargh
authors.forename: Alana
authors.initials: A
authors.lastname: Sulger
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Antognini
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000700:Analgesics / Q000494:pharmacology*; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001554:Benzene / Q000494:pharmacology; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D005464:Fluorobenzenes / Q000494:pharmacology; D005466:Fluorocarbons / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D006841:Hydrocarbons, Aromatic / Q000494:pharmacology*; D007796:Laminectomy; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D010146:Pain / Q000378:metabolism / Q000517:prevention & control*; D010147:Pain Measurement; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000700:Analgesics; D000777:Anesthetics; D005464:Fluorobenzenes; D005466:Fluorocarbons; D058785:GABA-A Receptor Agonists; D006841:Hydrocarbons, Aromatic; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; C081153:1,2-difluorobenzene; C003005:hexafluorobenzene; D001554:Benzene