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The effect of spinal ibuprofen on opioid withdrawal in the rat
S A Dunbar1, I G Karamov, H Buerkle
1Department of Anesthesiology, Tufts University School of Medicine, Baystate Medical Center, Springfield, MA 02115, USA.
Unlabelled:
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.
Implications:
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.
Insights
Spinal ibuprofen effectively blocks pain sensitivity during opioid withdrawal in rats. This stereospecific effect suggests a role for spinal prostaglandins in opioid abstinence symptoms.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Opioid abstinence syndrome involves complex physiological and behavioral changes.
- Hyperalgesia, an increased sensitivity to pain, is a significant manifestation of opioid withdrawal.
Purpose of the Study:
- To investigate the effect of spinally administered ibuprofen on behavioral signs of opioid withdrawal.
- To determine if ibuprofen's effect is stereospecific and dose-dependent.
Main Methods:
- Rats were infused with morphine for five days.
- Spinal ibuprofen (S(+) and R(-) enantiomers) or saline was administered before naloxone-induced antagonism.
- Behavioral manifestations of opioid withdrawal, including hyperalgesia, were assessed.
Main Results:
- Spinal ibuprofen S(+) dose-dependently and stereospecifically blocked opioid withdrawal-induced hyperalgesia.
- The R(-) enantiomer of ibuprofen did not significantly affect hyperalgesia.
- Other signs of opioid abstinence were not significantly altered by ibuprofen.
Conclusions:
- Spinal ibuprofen can effectively block hyperalgesia associated with opioid withdrawal.
- The stereospecificity of the effect suggests a role for spinal prostaglandins in modulating nociception during withdrawal.
- These findings may inform future therapeutic strategies for managing opioid abstinence.
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