Adenosine for pain control

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Abstract
The antinociceptive actions of adenosine and adenosine analogs in animal models has been known for more than 10 years. The recent development with regard to the pain modulatory effects of adenosine, primarily in clinical studies, has generated a renewed interest in this principle for pain control. This review summarizes the current knowledge in adenosine mediated pain modulation in acute and chronic conditions, with focus on studies in man. The endogenous compound adenosine has various modulatory effects in the peripheral and central nervous system, mediated through specific cell-surface associated receptors. The current view is that adenosine receptors of the A1-subtype are associated with a modulatory effect on pain transmission at spinal cord level. Animal studies have repeatedly demonstrated adenosine- and adenosine analog mediated inhibitory influences on presumed nociceptive reflex responses (1,2). These examinations in rodents have tested acute pain models involving tactile, pressure and heat stimulations. More recently, animal lesion models presumably reflecting chronic pain, has shown that adenosine analogs can suppress nociceptive behaviour both by systemic and intrathecal (i.t.) administration (3,4). Consequently, there is substantial evidence that adenosine can modulate nociceptive input. Further, it has been proposed that endogenous adenosine formation is involved in physiological pain control at the spinal cord level and that its release is involved in the action of opioid antinociception (1). Clinical studies have revealed that adenosine administration by bolus injection or by infusion at doses above 70 micrograms x kg-1 x min-1 is associated with pain symptoms from different parts of the body. This algogenic effect of higher doses of adenosine is probably related to sensitization/activation of peripheral nociceptive afferents (5).