Antihyperalgesic effects of delta opioid agonists in a rat model of chronic inflammation.
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 microl 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 mu opioid receptor agonists, DAMGO and morphine, and the delta 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 mu and delta 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 mu and delta 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 delta agonists in the hyperalgesia model suggests that delta opioid receptors in the brain are promising targets for the treatment of pain arising from chronic inflammation.
Fraser
G L
GL
AstraZeneca R&D Montréal, H4S 1Z9 Canada.
Gaudreau
G A
GA
Clarke
P B
PB
Ménard
D P
DP
Perkins
M N
MN
D000818:Animals; D004195:Disease Models, Animal; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009294:Narcotics / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010146:Pain; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000819:agonists
D009294:Narcotics; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D005620:Freund's Adjuvant