Intermittent shock titration task in the rhesus monkey and its validity as an analgesiometric procedure.
This study addressed issues concerning the validity of the shock titration paradigm by using focal, pulsed electrocutaneous stimulation and including unavoidable suprathreshold intensity stimuli among titratable, threshold intensity trials. In saline-treated monkeys, the distribution of response latencies on suprathreshold intensity trials, and the relationships between stimulus intensity and response latency, percent response or trial duration were consistent with those expected of painful stimuli. Morphine (0.3-3 mg/kg i.m.), meperidine (0.3-3 mg/kg i.m.) and pentazocine (1-6 mg/kg i.m.) each dose-dependently increased escape thresholds, but did not increase response latency on titratable trials. In contrast, diazepam (0.12-0.5 mg/kg i.m.) produced a dose-dependent increase in escape threshold and a significant increase in response latency on titratable trials. Sedative anxiolytics with muscle relaxant properties could therefore be distinguished from opioid analgesics. Morphine, meperidine, pentazocine and diazepam also produced a dose-dependent rightward shift in the frequency distribution of responses to suprathreshold stimuli at doses below those that significantly increased escape threshold. Thus, the antinociceptive effect of an opioid analgesic was detectable in the monkey in the clinically effective dose range. This paradigm permits analysis of drug effects at both escape threshold and suprathreshold intensities of noxious stimuli. The concomitant measurement of escape threshold and response latency on titratable trials with analysis of the frequency distribution of responses on suprathreshold trials yields a sensitive and discriminating analgesiometric procedure with potential application to rodent, as well as primate, species.
Bloss
J L
JL
Department of Central Nervous System Diseases Research, G.D. Searle & Co., Sokie, IL 60077.
Hammond
D L
DL
D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004597:Electroshock; D008251:Macaca / Q000502:physiology*; D008253:Macaca mulatta / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008614:Meperidine / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology*; D012107:Research Design
D000700:Analgesics; D009020:Morphine; D008614:Meperidine