Intrathecal ketorolac enhances antinociception from clonidine.
Although both alpha2-adrenergic agonists and cyclooxygenase inhibitors produce analgesia, their exact sites of action and interaction remain unclear. A previous report demonstrated a surprising inhibition of antinociception in rats from intrathecal clonidine by co-administered ketorolac. There are no other reports of interaction between these two classes of analgesics. We therefore reexamined this interaction, determining the effect of intrathecal clonidine and ketorolac alone and in combination in normal rats. Clonidine, but not ketorolac, produced antinociception to noxious hind paw thermal stimulation. The addition of ketorolac significantly enhanced the effect of clonidine, indicating a synergistic interaction for analgesia. Although the reasons for the discrepancy between this and the previous report are unclear, these results are consistent with previous studies that indicate an antinociceptive action of intrathecal alpha2-adrenergic agonists in the normal condition, a lack of such effect for cyclooxygenase inhibitors, and positive reinforcing effects of these two systems when co-stimulated.


CONCLUSIONS
Spinal injection of the alpha2-adrenergic agonist clonidine and the cyclooxygenase inhibitor ketorolac results in a synergistic interaction for antinociception in normal animals, suggesting that the combination of these drugs will enhance rather than detract from the analgesia of either alone.
Conklin
Dawn R
DR
Department of Anesthesiology and Center for the Study of Pharmacologic Plasticity in the Presence of Pain, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Eisenach
James C
JC
D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D003000:Clonidine / Q000627:therapeutic use*; D004357:Drug Synergism; D006358:Hot Temperature; D007278:Injections, Spinal; D020910:Ketorolac / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003000:Clonidine; D020910:Ketorolac