title: Rat dorsal horn nociceptive-specific neurons are more sensitive than wide dynamic range neurons to depression by immobilizing doses of volatile anesthetics: an effect partially reversed by the opioid receptor antagonist naloxone.
abstract: BACKGROUND
  The mechanism and site of action within the spinal cord by which volatile anesthetics produce immobility are not well understood. Little work has been done directly comparing anesthetic effects on neurons with specific functional characteristics that mediate transfer of nociceptive information within the spinal cord.
  
  
  METHODS
  Adult male rats were anesthetized and prepared for extracellular single-unit recordings from the lumbar dorsal horn. Nociceptive-specific (NS) and wide dynamic range (WDR) neurons were identified and noxious heat-evoked neuronal spike rates evaluated at 0.8 and 1.2 anesthetic minimum alveolar anesthetic concentration (MAC) halothane or isoflurane. In another group, noxious heat-evoked responses from NS neurons were evaluated at 0.8, 1.2 MAC halothane, and 1.2 MAC halothane plus IV naloxone (0.1 mg/kg).
  
  
  RESULTS
  Increasing halothane from 0.8 to 1.2 MAC reduced the heat-evoked neuronal responses of NS neurons (n = 9) from 827 +/- 122 (mean +/- se) to 343 +/- 48 spikes/min (P < 0.05) but not WDR neurons (n = 9), 617 +/- 79 to 547 +/- 78 spikes/min. Increasing isoflurane from 0.8 to 1.2 MAC reduced the heat-evoked neuronal response of NS neurons (n = 9) from 890 +/- 339 to 188 +/- 97 spikes/min (P < 0.05) but did not alter the response of WDR neurons (n = 9) in which evoked spike rate went from 576 +/- 132 to 601 +/- 119 spikes/min. In a separate group, the response of NS neurons went from 282 +/- 60 to 74 +/- 32 spikes/min (P < 0.05) when halothane was increased from 0.8 to 1.2 MAC. IV administration of naloxone increased the heat-evoked response to 155 +/- 46 spikes/min (P < 0.05).
  
  
  CONCLUSIONS
  NS but not WDR neurons in the lumbar dorsal horn are depressed by peri-MAC increases of halothane and isoflurane. This depression, at least with halothane, can be partially reversed by the opioid antagonist naloxone. Given that opioid receptors are not likely involved in the mechanisms by which volatile anesthetics produce immobility, this suggests that, although the neuronal depression is of substantial magnitude and occurs concurrent to the production of immobility, it may not play a major role in the production of this anesthetic end point.
authors.affiliation: Departments of Anesthesiology and Pain Medicine, University of California, Davis, California 95616, USA. lsbarter@ucdavis.ed
authors.forename: Linda S
authors.initials: LS
authors.lastname: Barter
authors.forename: Earl E
authors.initials: EE
authors.lastname: Carstens
authors.forename: Steven L
authors.initials: SL
authors.lastname: Jinks
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Antognini
mesh_terms: D018685:Anesthetics, Inhalation / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004594:Electrophysiology; D006221:Halothane / Q000494:pharmacology; D006358:Hot Temperature; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D008839:Microelectrodes; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D009619:Nociceptors / Q000187:drug effects*; D020671:Posterior Horn Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018685:Anesthetics, Inhalation; D009292:Narcotic Antagonists; D009270:Naloxone; D007530:Isoflurane; D006221:Halothane