Antihyperalgesic effects of δ opioid agonists in a rat model of chronic inflammation
Article first published online: 30 JAN 2009
2000 British Pharmacological Society
British Journal of Pharmacology
Volume 129, Issue 8, pages 1668–1672, April 2000
How to Cite
Fraser, G. L., Gaudreau, G.-A., Clarke, P. B. S., Ménard, D. P. and Perkins, M. N. (2000), Antihyperalgesic effects of δ opioid agonists in a rat model of chronic inflammation. British Journal of Pharmacology, 129: 1668–1672. doi: 10.1038/sj.bjp.0703248
- Issue published online: 30 JAN 2009
- Article first published online: 30 JAN 2009
- (Received September 23, 1999, Revised January 1, 2000, Accepted January 18, 2000)
- μ opioid receptor;
- δ opioid receptor;
- chronic inflammation;
- Freund's Adjuvant
Opioid receptors in the brain activate descending pain pathways to inhibit the nociceptive response to acute noxious stimuli. The aim of the present study was to clarify the role of supraspinal opioid receptors in modulating the nociceptive response to persistent inflammation in rats.
Subcutaneous administration of 50 μl of complete Freund's Adjuvant (CFA) into the plantar surface of the hindpaw induced a significant decrease in paw withdrawal latency to thermal stimuli (P<0.01) at 24 h post-injection.
Intracerebroventricular (i.c.v.) administration of the μ opioid receptor agonists, DAMGO and morphine, and the δ opioid receptor agonists, deltorphin II and SNC80, significantly reversed the hyperalgesic response associated with peripheral inflammation in a dose-dependent manner (P<0.0001).
The μ and δ agonists also significantly attenuated the antinociceptive response to acute thermal stimulation in rats (P<0.001). However, deltorphin II and SNC80 were less potent, and in the case of SNC80 less efficacious, in modulating the response to acute thermal nociception in comparison to hyperalgesia associated with persistent inflammation.
These results indicate that μ and δ opioid receptors in the brain modulate descending pain pathways to attenuate the nociceptive response to acute thermal stimuli in both normal and inflamed tissues. The heightened response to δ agonists in the hyperalgesia model suggests that δ opioid receptors in the brain are promising targets for the treatment of pain arising from chronic inflammation.
British Journal of Pharmacology (2000) 129, 1668–1672; doi:10.1038/sj.bjp.0703248