Influence of nociception and stress-induced antinociception on genetic variation in isoflurane anesthetic potency among mouse strains.
BACKGROUND
Genetic background influences anesthetic potency to suppress motor response to noxious stimulation (minimum alveolar concentration [MAC]) as well as nociceptive sensitivity in unmedicated animals. However, the influence on MAC of baseline sensitivity to the noxious stimuli used to assess MAC has virtually never been studied. The authors assessed room air nociceptive sensitivity and isoflurane MAC in multiple mouse strains. Isoflurane requirement for loss of righting response (MACLORR) was also measured.


METHODS
One outbred and 10 inbred mouse strains were tested for latency to respond (in room air) to a tail clip (either 500 g or 2,000 g). Naive mice of the same 11 strains were tested for isoflurane MAC and MACLORR. To assess the role of opioid-mediated stress-induced antinociception, mice were also tested for nociceptive sensitivity after injection of naloxone (10 mg/kg) or saline.


RESULTS
Robust strain differences were observed for all measures. The authors found that tail-clip latency (using a 500-g or 2,000-g clip, respectively) correlated significantly with MAC (r = -0.76 and -0.58, respectively) but not MACLORR (r = -0.10 and -0.26). Naloxone produced strain-dependent reductions in open air tail-clip latencies, and these reductions were also strongly correlated with MAC (r = -0.67 and -0.71).


CONCLUSIONS
The authors suggest that genetic variability in isoflurane MAC (but not MACLORR) may reflect genetic variability in the underlying sensitivity to the noxious stimulus being used to measure MAC. This variable sensitivity to nociception in the awake state is at least partially mediated by endogenous antinociceptive mechanisms activated by the tail-clip stimulus itself.
Mogil
Jeffrey S
JS
Department of Psychology and Centre for Research on Pain, McGill University, Montreal, Quebec, Canada.
Smith
Shad B
SB
O'Reilly
Meghan K
MK
Plourde
Gilles
G
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D005260:Female; D014644:Genetic Variation; D007530:Isoflurane / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009270:Naloxone / Q000494:pharmacology; D010147:Pain Measurement / Q000379:methods*; D011650:Pulmonary Alveoli / Q000378:metabolism; D013045:Species Specificity; D013315:Stress, Psychological / Q000503:physiopathology*; D013623:Tail / Q000098:blood supply
D018685:Anesthetics, Inhalation; D009270:Naloxone; D007530:Isoflurane