Hypoalgesic effect of caffeine in experimental ischemic muscle contraction pain

It has been theorized that adenosine is a leading candidate for the metabolite responsible for ischemic muscle pain. The purpose of this study was to determine the effect of the non-selective adenosine receptor antagonist, caffeine, on ischemic skeletal muscle contraction pain. Seven healthy adult volunteers with no history of pain disorders, systemic disease, or habitual caffeine use, were chosen for the two-session, cross-over, double-blind study. Every subject received either 200 mg of caffeine (NoDoz, Bristol-Myers) or identical placebo 1 hour before each of the two trials. Ischemia of the forearm was achieved by inflation of a blood pressure cuff to 250 mm Hg. Forearm muscle activity was generated by performance of wrist curis using a 5-gram bar at a rate of 40 cycles per minute. Pain was rated at 15-second intervals for 1 minute using a visual analog scale (0 to 10) with verbal descriptors. Significance was determined by univariate and multivariate analyses of variance and covariance including repeated measures. Pain ratings at 15 seconds in the caffeine trial were significantly lower (P < 0.02) than those in the placebo trial. This effect continued at 30 seconds (P < 0.05). However, by 45 seconds, pain in the caffeine trial was not significantly lower (P = 0.4) than that in the placebo trial. These results show that high-dose caffeine exhibits considerable analgesic efficacy in experimental muscle pain, adding support for a role of adenosine in producing ischemic muscle contraction pain.