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ANALGESIA

Intrathecal Administration of a Cylcooxygenase-1, but Not a Cyclooxygenase-2 Inhibitor, Reverses the Effects of Laparotomy on Exploratory Activity in Rats

Thomas J. Martin, PhD^*, Nancy L. Buechler, BS^*, and James C. Eisenach, MD

From the Departments of *Physiology and Pharmacology and Anesthesiology, the Center for the Study of Pharmacologic Plasticity in the Presence of Pain, Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Address correspondence and reprint requests to Thomas J. Martin, PhD, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157. Address e-mail to tjmartin{at}wfubmc.edu.

Abstract

Studies of hypersensitivity to mechanical stimuli after incisional surgery suggest that cyclooxygenase (COX)-1, but not COX-2, in the spinal cord participates in postoperative pain. In the current study, we sought to determine the role of COX isoenzymes after laparotomy, examining spontaneous exploratory behavior rather than withdrawal reflexes. Adult male Sprague-Dawley rats underwent subcostal laparotomy surgery under isoflurane anesthesia or received anesthesia without surgery. Exploratory locomotor activity was measured on the first postoperative day after intrathecal injection of dimethyl sulfoxide (vehicle) or COX-1 (SC-560) or COX-2 (NS-398) inhibitors. Laparotomy reduced ambulation, rearing, and rapid small movements (stereotypy) similarly in animals without intrathecal catheters and those receiving intrathecal vehicle control. SC-560 produced a dose-related return to normal exploratory behavior with complete return at doses of 20 µg and larger. In contrast, NS-398 in doses up to 50 µg failed to increase exploratory behavior. These data with exploratory behavior and laparotomy agree with studies with reflexive withdrawal responses after incisional surgery and indicate that COX-1 inhibition reduces pain responses after surgery. Spinal COX-1 inhibition completely restores exploratory activity, including rearing behavior that stretches the abdominal muscles. These data suggest that targeting COX-1 in the spinal cord may produce postoperative analgesia.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999