title: Isoflurane differentially modulates medullary on and off neurons while suppressing hind-limb motor withdrawals.
abstract: BACKGROUND
  Isoflurane acts primarily in the spinal cord to block movement; however, it is unclear how supraspinal sites might contribute to anesthetic effects on quantified parameters of movement such as force.
  
  
  METHODS
  The authors investigated the effects of isoflurane on spontaneous and noxious heat-evoked activity of nociceptive reflex-modulating ON and OFF cells in the rostral ventromedial medulla of rats. Single ON or OFF neurons were recorded simultaneously with hind-limb withdrawal force elicited by graded noxious thermal hind paw stimulation. Isoflurane concentrations were administered in reference to each animal's minimum alveolar concentration (MAC) of isoflurane.
  
  
  RESULTS
  From 0.65 to 1.15 MAC, isoflurane dose-dependently reduced spontaneous activity of ON cells by 70% (P < 0.001). OFF-cell spontaneous activity was dose-dependently increased 138% (P < 0.001). ON-cell heat-evoked activity was depressed 95% by isoflurane from 0.65 to 1.15 MAC (P < 0.001). Isoflurane-induced changes in ON- and OFF-cell activity paralleled similar reductions in withdrawal force, with the largest change in both neuronal activity and withdrawal force occurring between 0.85 and 1.15 MAC. For the lowest stimulus temperature, excitatory responses of ON cells and inhibitory responses of OFF cells were significantly greater for trials in which withdrawals occurred than for trials in which no withdrawal occurred, suggesting that responses in both classes of neurons were related to movement rather than the stimulus alone.
  
  
  CONCLUSIONS
  The results show that isoflurane modulation of ON- and OFF-cell activity corresponds to anesthetic-induced reductions in hind-limb withdrawal force, and therefore, the effects of isoflurane on these classes of neurons in rostral ventromedial medulla might contribute to motor depression.
authors.affiliation: Department of Anesthesiology and Pain Medicine, University of California, Davis, TB 170, Davis, California 95616, USA. sljinks@ucdavis.edu
authors.forename: Steven L
authors.initials: SL
authors.lastname: Jinks
authors.forename: Earl
authors.initials: E
authors.lastname: Carstens
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Antognini
mesh_terms: D000818:Animals; D006614:Hindlimb / Q000187:drug effects* / Q000502:physiology; D006358:Hot Temperature / Q000009:adverse effects; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007530:Isoflurane