Nociceptin and the ORL-1 ligand [Phe(1)psi (CH2-NH)Gly(2)]nociceptin(1-13)NH2 exert anti-opioid effects in the Freund's adjuvant-induced arthritic rat model of chronic pain

1 Stimulation of the opioid receptor-like1 (ORL-1) receptor by nociceptin ( NC) produces hyperalgesia and reverses the antinociceptive effects induced by opioids. Most studies concerning the central effects of NC were conducte d using acute pain models. The role NC may play in chronic inflammation rem ains unelucidated. 2 The present study was undertaken to assess the action of NC in the Freund 's adjuvant-induced monoarthritic rat model. The effects of drugs known to act as analgesics in this model were evaluated. The effects of NC, NCNH2. a nd the ORL-1 ligand, [Phe(1)Psi(CH2-NH)Gly(2)]NC(1-13)NH2 ([FIG]NC(1-13)NH, ), were also studied alone or in association with morphine. 3 NC (1-30 nmol, i.c.v.) was inactive, whilst NCNH2 (10 nmol, i.c.v.) exert ed hyperalgesic effects (-4.5+/-0.9 vs -0.7+/-0.8 s of vehicle-treated anim als). [F/G]NC(1-13)NH2 (0.01-10 nmol, i.c.v.) induced hyperalgesia in the a rthritic paw (--3.3 +/- 0.6 vs --0.3 +/- 0.5 s of vehicle-treated animals; 10 nmol). 4 Both NC (0.01-10 nmol, i.c.v.) and [F/G]NC(1-13)NH2 (0.01-1 nmol, i.c.v), 30 min after morphine (3 mg kg(-1), s.c. induced an immediate and short-li ved reversal of morphine effects (2.6 +/- 0.3 vs 10.4 +/- 1.0 and 1.2 +/- 1 .5 vs 9.3 +/- 1.1 s of morphine alone, respectively), therefore displaying anti-opioid activity. 5 In the Freund's adjuvant-induced rat model of arthritis, both NC and [F/G ]NC(1-13)NH2 act as anti-opioid peptides. Furthermore, NCNH2 and [F/G]NC(1- 13)NH2 induce hyperalgesia when given alone. Further investigations and the identification of a centrally acting ORL-1 antagonist are necessary to bet ter understand the role of NC in pain mechanisms.