Pharmacology of intrathecal adrenergic agonists: cardiovascular and nociceptive reflexes in halothane-anesthetized rats.

The effects of intrathecally administered adrenergic agonists (alpha-1-methoxamine, alpha-2-dexmedetomidine, clonidine, and ST-91, beta-isoproterenol) on nociceptive (tail-flick reflex) and cardiovascular changes (blood pressure and heart rate) evoked by immersing the tail in 53 degrees C water were examined in rats anesthetized with halothane (0.75%) and in which intrathecal catheters had been chronically implanted. Administration of intrathecal alpha-2, but not alpha-1 or beta agonists, produced a dose-dependent block of the tail-flick and evoked cardiovascular responses with the order of activity being as follows: dexmedetomidine greater than clonidine greater than ST-91 much greater than methoxamine greater than or equal to isoproterenol. These effects were readily reversed by the alpha-2 antagonist idazoxan. Intravenously administered dexmedetomidine at a dose that is active when given intrathecally (0.33 micrograms) was without effect on either the tail-flick or the evoked cardiovascular responses. Without drugs, the halothane MAC was 1.23 +/- 0.07%. In the presence of intrathecally administered dexmedetomidine (0.33 micrograms), the MAC was significantly reduced to 0.9 +/- 0.09%. The intrathecal administration of alpha-2 agonists resulted in a rapid decrease in resting blood pressure and heart rate with the magnitude of hypotension being as follows: dexmedetomidine greater than clonidine greater than ST-91. These data suggest a potent spinal alpha-2-receptor-mediated modulation of somatomotor and autonomic responses to pain.