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 pain significantly greater than normal saline after 15 sec (T0) (29 +/- 13 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). There was evidence of hyperalgesia to mechanical and heat stimuli at the injection site (primary hyperalgesia). There was no evidence of mechanical hyperalgesia in the cutaneous area surrounding the injected site (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 bamiphylline, a rather selective antagonist of A1 adenosine receptors, differently from placebo, completely suppressed the adenosine-induced pain after 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 and mechanical stimuli was detected at the bamiphylline site. The adenosine-induced erythematous area was wider at the bamiphylline pre-injected site than at the placebo pre-injected site (173 +/- 114 vs. 119 +/- 85 mm2). We conclude that adenosine is an algogenic substance able to activate not only visceral but also cutaneous nociceptors. Furthermore our results suggest that the activation of nociceptors is at least partially mediated by A1 adenosine receptors.