ANALGESIC EFFECT OF BAMIPHYLLINE ON PAIN INDUCED BY INTRADERMAL INJECTION OF ADENOSINE

Adenosine is known to cause pain when injected intravenously or intra- arterially. We have conducted a double-blind placebo-controlled study by injecting adenosine intradermally in 6 healthy subjects (5 male, 1 female; age: 27-34 years). Pain was assessed using the visual analogue scale. The intradermal injection of 2 mumol of adenosine produced pai n significantly greater than normal saline after 15 sec (T0) (29 +/- 1 3 vs. 7 +/- 6 mm, P = 0.004), 1 min after T0 (13 +/- 9 vs. 0 +/- 0 mm, P = 0.002) and 2 min after T0 (4.5 +/- 5 vs. 0 +/- 0 mm, P < 0.05). T here was evidence of hyperalgesia to mechanical and heat stimuli at th e injection site (primary hyperalgesia). There was no evidence of mech anical hyperalgesia in the cutaneous area surrounding the injected sit e (secondary hyperalgesia). In all cases the intradermal injection of adenosine produced local hyperemia (mean surface are: 147 +/- 69 mm2) which was absent after placebo injection. The pre-injection of bamiphy lline, a rather selective antagonist of A1 adenosine receptors, differ ently from placebo, completely suppressed the adenosine-induced pain a fter 15 sec (T0) (15 +/- 10 vs. 0 +/- 0 mm, P = 0.002) and 1 min after T0 (9 +/- 7 vs. 0 +/- 0 mm, P = 0.002). No anesthesia to heat, cold a nd mechanical stimuli was detected at the bamiphylline site. The adeno sine-induced erythematous area was wider at the bamiphylline pre-injec ted site than at the placebo pre-injected site (173 +/- 114 vs. 119 +/ - 85 mm2). We conclude that adenosine is an algogenic substance able t o activate not only visceral but also cutaneous nociceptors. Furthermo re our results suggest that the activation of nociceptors is at least partially mediated by A1 adenosine receptors.