Effects of an opiate on cold-induced pain and the CNS in healthy volunteers.
The analgesic activity of an opiate was studied in 12 healthy volunteers using a cold-induced pain (CP) model. Effects on the central nervous system (CNS) were also measured. According to a double-blind, randomised, balanced, cross-over design with an interval of 7 days between occasions, subjects received single oral doses of 2, 4 and 8 mg dipipanone (D2, D4, D8) and a placebo. The CP test and a battery of measurements of CNS function were performed 3 times on each study day, once before and again 1.5 h and 3.0 h after treatment. Mean pain cores on a computerised visual analogue scale were significantly higher after placebo than those after 4 mg (P less than 0.05) and 8 mg (P less than 0.01) dipipanone and a dose-response relationship was evident. The opiate did not affect baseline blood pressure before the CP test but the hypertensive response to the painful cold stimulus was diminished 3 h after D8. Scores on scales for subjective assessment of alertness were significantly reduced 3 h after the 8 mg dose and pupil diameters were significantly smaller after all 3 doses of dipipanone. Body sway and visual near points were not significantly altered by the opiate. It is concluded that the CP test is a sensitive model for measurement of opiate-induced analgesia in healthy volunteers. Pupillometry and visual analogue scales are useful for the assessment of central effects of opiates.
Posner
John
J
Department of Clinical Pharmacology, Wellcome Research Laboratories, Beckenham, KentU.K.
Telekes
Andras
A
Crowley
Dominic
D
Phillipson
Richard
R
Peck
Anthony W
AW
D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D003080:Cold Temperature / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008691:Methadone / Q000031:analogs & derivatives* / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D011897:Random Allocation
D000701:Analgesics, Opioid; D008691:Methadone; C007527:dipipanone