Evidence for an exclusive antinociceptive effect of nociceptin/orphanin FQ, an endogenous ligand for the ORL1 receptor, in two animal models of neuropathic pain.
Nociceptin/orphanin FQ (noci/OFQ), the endogenous ligand for the orphan ORL1 (opioid receptor-like1), has been shown to be anti- or pronociceptive and modify morphine analgesia in rats after central administration. We comparatively examined the effect of noci/OFQ on hyperalgesia and morphine analgesia in two experimental models of neuropathic pain: diabetic (D) and mononeuropathic (MN) rats. Noci/OFQ, when intrathecally (i.t.) injected (0.1, 0.3, or 1, to 10 microg/rat) was ineffective in normal rats, but reduced and suppressed mechanical hyperalgesia (paw-pressure test) in D and MN rats, respectively. This spinal inhibitory effect was suppressed by naloxone (10 microg/rat, i.t.) in both models. Combinations of systemic morphine with spinal noci/OFQ resulted in a strong potentiation of analgesia in D rats. In MN rats, an isobolographic analysis showed that the morphine+noci/OFQ association (i.t.) suppressed mechanical hyperalgesia in a superadditive manner. In summary, the present findings reveal that spinal noci/OFQ produces a differential antinociception in diabetic and traumatic neuropathic pain according to the etiology of neuropathy, an effect possibly mediated by opioid receptors. Moreover, noci/OFQ combined with morphine produces antinociceptive synergy in experimental neuropathy, opening new opportunities in the treatment of neuropathic pain.
EMI 9904 INSERM/UdA, Department of Pharmacology, Faculty of Pharmacy, 28 place Henri Dunant, BP 38, 63001 Clermont-Ferrand Cedex 1, France. christine.courteix@u-clermont1.fr
Christine
C
Courteix
Marie-Ange
MA
Coudoré-Civiale
Anne-Marie
AM
Privat
Teresa
T
Pélissier
Alain
A
Eschalier
Joseph
J
Fialip
D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006930:Hyperalgesia / Q000503:physiopathology; D008297:Male; D020422:Mononeuropathies / Q000378:metabolism / Q000503:physiopathology*; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000502:physiology*; D010146:Pain / Q000378:metabolism / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism*; D012584:Sciatic Nerve / Q000293:injuries; D013311:Streptozocin; D013997:Time Factors; D014828:Vocalization, Animal / Q000187:drug effects; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D009020:Morphine; D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D013311:Streptozocin; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat