Antinociceptive interactions between intrathecally administered alpha noradrenergic agonists and...

Recently, it has been shown that intrathecal injection of norepinephrine and the mixed A1/A2 adenosine agonist 5'-N-ethylcarboxamide adenosine (NECA) interact in a supra-additive manner to produce antinociception. The present studies were designed to determine whether alpha 1 or alpha 2 noradrenergic receptors are involved in producing the antinociception induced by NECA and norepinephrine. The results indicated that intrathecal injection of NECA (0.97-4.9 nmol), the alpha 2 noradrenergic agonist clonidine (3.8-375 nmol), or the alpha 1 agonist phenylephrine (4.9-73.4 nmol) produced dose-dependent antinociception in rats. Furthermore, intrathecal injection of subeffective doses of NECA and clonidine interacted supra-additively to produce potent antinociception. In contrast, no supra-additive interaction was observed between NECA and phenylephrine. The supra-additive interaction of NECA and clonidine did not appear to result from alterations in cardiovascular tone because changes in blood pressure and nociceptive thresholds were not correlated in time. These results suggest that the noradrenergic component of the supra-additive interaction between adenosine A2 receptor agonists and noradrenergic agonists is mediated by alpha 2 noradrenergic receptors.