The effect of spinal ibuprofen on opioid withdrawal in the rat

• Published in: Anesthesia and analgesia Vol. 91; no. 2; pp. 417 - 422
• Main Authors: DUNBAR, S. A, KARAMOV, I. G, BUERKLE, H
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 01.08.2000
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Behavior, Animal - drug effects; Biological and medical sciences; Drug toxicity and drugs side effects treatment; Hyperalgesia - chemically induced; Hyperalgesia - prevention & control; Ibuprofen - administration & dosage; Injections, Spinal; Male; Medical sciences; Morphine - adverse effects; Naloxone - administration & dosage; Narcotic Antagonists - administration & dosage; Narcotics - adverse effects; Pain Threshold; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Reaction Time; Substance Withdrawal Syndrome - drug therapy; Toxicity: nervous system and muscle; Prostaglandin; Rat; Toxicity; Rodentia; Morphine; Opiates; Narcotic analgesic; Intrathecal administration; Hyperalgesia; Non steroidal antiinflammatory agent; Stereoselectivity; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Enantiomer; Ibuprofen; Arylpropionic acid derivatives; Withdrawal syndrome
• ISSN: 0003-2999; 1526-7598
• DOI: 10.1097/00000539-200008000-00035

This study examines the effect of spinal ibuprofen on the behavioral manifestations associated with the opioid abstinence syndrome. Rats (n = 8 per group) were infused for 5 days with morphine and then pretreated with a spinal bolus dose of ibuprofen before systemic naloxone antagonism (300 microg). Groups included ibuprofen S(+) 1. 36, 13.6, and 136 nmol, and ibuprofen R(-) 136 nmol. A separate group of saline-infused rats was given ibuprofen S(+) 136 nmol before naloxone antagonism. Ibuprofen S(+), but not R(-), dose-dependently and stereospecifically blocked opioid withdrawal hyperalgesia but did not significantly alter other signs of the opioid abstinence syndrome. We conclude that hyperalgesia associated with opioid withdrawal can be blocked by spinally administered ibuprofen, and suggest that there may be a role for spinal prostaglandins in the enhancement of nociception observed in association with the opioid abstinence syndrome. This study shows that spinal ibuprofen blocks opioid withdrawal hyperalgesia in the rat in a stereospecific fashion, implicating the likely release of spinal prostaglandins during withdrawal and their possible role as neuromodulators in the enhancement of nociception that accompanies this phenomenon.