A new laser pain threshold model detects a faster onset of action from a liquid formulation of 1 g paracetamol than an equivalent tablet formulation.
OBJECTIVE
To discover whether a new infra-red laser method could detect a change in pain threshold after as mild an analgesic as paracetamol and whether an effervescent liquid formulation produced a faster onset of action than tablets.


METHODS
This double-blind, placebo controlled randomized study used a portable, infra-red laser to measure "first pain" thresholds on the nondominant forearm in 12 normal volunteers before and after 1 g of paracetamol or placebo. The mean of six recordings was determined three times before dosing, the first being used as a familiarization procedure, and 14 times after dosing.


RESULTS
We detected a small (2%), statistically significant difference in pain threshold between a liquid formulation of paracetamol and placebo at 30 and 60 min (P = 0.004 and P = 0.001), but not between tablets and placebo. Liquid also increased the threshold significantly compared with tablets at 60 min (P = 0.01).


CONCLUSIONS
To detect such a small increase in pain threshold requires a highly consistent measure and the coefficient of variation was 2% for the study overall, surprisingly low for a subjective phenomenon. The reasons for this include minimizing reflectance by blacking the skin, using a nonhairy site, averaging six data points at each sample time and controlling closely the ambient conditions and the subjects' preparation for studies.
Sutton
J Andrew
JA
Guildford Clinical Pharmacology Unit Ltd, Royal Surrey County Hospital, Guildford, GU2 7XX, Surrey, UK.
Gillin
W P
WP
Grattan
T J
TJ
Clarke
G D
GD
Kilminster
S G
SG
D000082:Acetaminophen / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000704:Analysis of Variance; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D016001:Confidence Intervals; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007259:Infrared Rays / Q000009:adverse effects; D007834:Lasers / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D017288:Pain Threshold / Q000187:drug effects*; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics; D013607:Tablets; D013810:Therapeutic Equivalency
D018712:Analgesics, Non-Narcotic; D002214:Capsules; D019999:Pharmaceutical Solutions; D013607:Tablets; D000082:Acetaminophen