Systemic, but not intrathecal ketorolac is antinociceptive to uterine cervical distension in rats

Abstract

Cyclooxygenase inhibitors demonstrate effective antinociception in many clinical and experimental pain models. Acute uterine cervical distension (UCD) forms the basis for obstetric and some gynecologic pain, and acute UCD in rats results in nocifensor reflexes which are inhibited by morphine in animals lacking, but not in animals with circulating estrogen. We studied the antinociceptive effect of intravenous and intrathecal injection of the cyclooxygenase inhibitor, ketorolac in acute UCD rats and its dependency on estrogen. Virgin rats received estrogen or placebo treatment for 1 week following oviarectomy. An intrathecal catheter was inserted for drug administration. Rats were anesthetized, then the electromyographic response in the rectus abdominus muscle and mean arterial blood pressure change to UCD was recorded before and with cumulative dosing of intravenous or intrathecal ketorolac. Intravenous ketorolac produced dose dependent inhibition of the responses to UCD, but intrathecal ketorolac was ineffective at the maximum test dose (300 μg). Estrogen replacement did not affect the stimulus response or maximum efficacy of ketorolac. Unlike morphine, which reduces response to UCD by spinal and supraspinal mechanisms and whose action is blocked by estrogen, the cyclooxygenase inhibitor, ketorolac acts at an estrogen-independent, non spinal site.