Analgesic effects of adenosine in Syndrome X are counteracted by theophylline: a double-blind placebo-controlled study

It has been proposed that adenosine mediates ischaemic pain in humans. Pati ents with cardiac Syndrome X are hypersensitive to potential pain stimuli, including adenosine. On the other hand, recent findings suggest that low-do se adenosine infusion may have analgesic effects. Our aim was to test two h ypotheses: (1) that the analgesic effect of adenosine is peripheral in orig in, and (2) that part of the hypersensitivity to pain of patients with card iac Syndrome X results from a disturbed mechanism of adenosine analgesia. A total of 12 female Syndrome X patients and eight healthy age-matched femal e controls were studied in a randomized, double-blind and placebo-controlle d study. Adenosine (70 mu g/min) or placebo was infused into the forearm vi a an intra-arterial catheter. After 15 min of infusion, a tourniquet on the upper arm was inflated to 225 mmHg to ensure arterial occlusion. The patie nt then carried out dynamic handgrip work at 60 Hz. Pain or discomfort in t he forearm was estimated continuously according to the Borg CR-10 scale. Af ter the first test, theophylline was infused for 10 min intravenously at a dose of 5 mg/kg body weight. The ischaemic forearm test was then repeated. On a second occasion, the procedure was repeated with the opposite treatmen t (adenosine/placebo). Only six of 12 Syndrome X patients completed the pro tocol because of pain during the catheterization procedure or an inability to establish an intra-arterial line. The time to onset of pain in the worki ng, ischaemic forearm was greater for subjects treated with adenosine than for those treated with placebo, both in those Syndrome X patients who toler ated catheterization (49 +/- 27 s compared with 32 +/- 18 s; P < 0.03) and in healthy controls (40 +/- 19 s compared with 16 +/- 8; P < 0.02). The tim e to maximum pain, limiting ischaemic work, was also greater with adenosine pretreatment both in Syndrome X patients (137 +/- 28 s compared with 106 /- 28 s; P < 0.03) and in healthy controls (109 +/- 31 compared with 82 +/- 18 s; P < 0.01). After infusion of theophylline there was no difference be tween adenosine and placebo in either group. Intraarterially infused adenos ine had similar peripheral analgesic effects on experimentally induced musc ular ischaemia in those female Syndrome X patients who tolerated intra-arte rial catheterization and in healthy controls. Thus adenosine analgesia is c ounteracted by theophylline, suggesting that the effect is mediated by memb rane-bound peripheral adenosine receptors.