Antagonism of Antinociception Produced by Intrathecal Clonidine by Ketorolac in the Rat: The Role of the Opioid System

Abstract

The management of severe pain may require “balanced analgesia,” involving the use of analgesics with different modes of action. Clonidine, an α2-adrenoreceptor agonist produces analgesia by itself as well as when given with morphine and local anesthetics. Ketorolac is indicated for the management of moderately severe acute pain and causes analgesia equivalent to morphine. This study was designed to investigate whether the addition of ketorolac promotes antinociception produced by intrathecal administration of clonidine in male Sprague-Dawley rats. Intrathecal injection of clonidine (1–30 μg) induced a dose-dependent increase in antinociception as measured by the tail flick (TF) and hot plate tests. Ketorolac alone (150–600 μg) increased the antinociception by 50%–60% only in the TF test. Ketorolac (10 μg) decreased clonidine (10 μg)-induced antinociception from 69.1% ± 7.8% to 23.5% ± 1.6% (P P Clonidine and ketorolac are two important drugs used to give pain relief to patients. We observed that ketorolac inhibits clonidine-induced analgesia in the rat. We recommend that this drug interaction should be taken into account when both clonidine and ketorolac are used together to alleviate pain in patients.