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Antihyperalgesic effects of δ opioid agonists in a rat model of chronic inflammation
Author(s) -
Fraser Graeme L,
Gaudreau GenevièveAnne,
Clarke Paul B S,
Ménard Daniel P,
Perkins Martin N
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703248
Subject(s) - opioid , hyperalgesia , nociception , damgo , medicine , pharmacology , μ opioid receptor , δ opioid receptor , noxious stimulus , chronic pain , agonist , inflammation , receptor , stimulation , opioid receptor , endocrinology , psychiatry
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