Spinal vs. supraspinal antinociceptive activity of the adenosine A(1) receptor agonist cyclopentyl-adenosine in rats with inflammation.

The adenosine A(1) receptor is involved in spinal cord antinociception. As its role at supraspinal sites is not well known, we studied the systemic effects of its agonist N-cyclopentyl-adenosine (CPA) in single motor units from adult-spinalized, intact and sham-spinalized rats. CPA was not effective after spinalization, but it was very effective in intact animals (ID50: 92+/-1.3 microg/kg, noxious pinch) and over 10-fold more potent in sham-spinalized animals (ID50 of 8.3+/-1 microg/kg). Wind-up was also inhibited by CPA. We also studied the effect of CPA in the immature spinal cord preparation, where CPA dose-dependently inhibited responses to low (IC50s: 9+/-0.7 and 7.7+/-1.3 nM) and high intensity stimulation (IC50s: 4.9+/-0.5 and 12.1+/-2 nM). We conclude that the integrity of the spinal cord is crucial for the antinociceptive activity of systemic CPA in adult rats but not in immature rats, not yet influenced by a completely developed supraspinal control.