Accepted manuscript
Antinociception produced by nonsteroidal anti-inflammatory drugs in female vs male rats
Behavioural pharmacology, Vol.32(2-3), pp.153-169
04/01/2021
PMID: 33290343
Abstract
The primary aim of this study was to examine sex differences in acute antinociceptive and anti-inflammatory effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in rats. Complete Freund's adjuvant (CFA) was administered to adult Sprague-Dawley rats to induce pain and inflammation in one hindpaw; 2.5 h later, vehicle or a single dose of the NSAIDs ibuprofen (1.0-32 mg/kg) or ketoprofen (0.1-10 mg/kg), or the COX-2-preferring inhibitor celecoxib (1.0-10 mg/kg) was injected i.p. Mechanical allodynia, heat hyperalgesia, biased weight-bearing, and hindpaw thickness were assessed 0.5-24 h after drug injection. Ibuprofen and ketoprofen were more potent or efficacious in females than males in reducing mechanical allodynia and increasing weight-bearing on the CFA-injected paw, and celecoxib was longer-acting in females than males on these endpoints. In contrast, ketoprofen and celecoxib were more potent or efficacious in males than females in reducing hindpaw edema. When administered 3 days rather than 2.5 h after CFA, ketoprofen (3.2-32 mg/kg) was minimally effective in attenuating mechanical allodynia and heat hyperalgesia, and did not restore weight-bearing or significantly decrease hindpaw edema, with no sex differences in any effect. Neither celecoxib nor ketoprofen effects were significantly attenuated by cannabinoid receptor 1 or 2 (CB1 or CB2) antagonists in either sex. These results suggest that common NSAIDs administered shortly after induction of inflammation are more effective in females than males in regard to their antinociceptive effects, whereas their anti-inflammatory effects tend to favor males; effect sizes indicate that sex differences in NSAID effect may be functionally important in some cases.
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Details
- Title
- Antinociception produced by nonsteroidal anti-inflammatory drugs in female vs male rats
- Creators
- Rebecca M. Craft - Washington State UniversityKelly A. Hewitt - Washington State UniversityStevie C. Britch - University of Kentucky
- Publication Details
- Behavioural pharmacology, Vol.32(2-3), pp.153-169
- Academic Unit
- Psychology, Department of
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 17
- Grant note
- Herbert L. Eastlick Professorship Psychopharmacology Research Fund T32 DA035200 / National Institute on Drug Abuse; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission
- Identifiers
- 99900907905101842
- Language
- English
- Resource Type
- Accepted manuscript