title: Effects of intraplantar nocistatin and (±)-J 113397 injections on nociceptive behavior in a rat model of inflammation.
abstract: Nocistatin (NST) and Nociceptin/Orphanin FQ (N/OFQ) are derived from the same precursor protein, pre-proN/OFQ, and exert opposite effects on the modulation of pain signals. However, the role of the peripheral N/OFQ and the NOP receptor, which is located at the endings of sensory nerves, in inflammatory pain was not ascertained. NST administered intrathecally (i.t.) prevented the nociceptive effects induced by i.t. N/OFQ and PGE₂. Moreover an up regulation of N/OFQ was shown in the rat in response to peripheral inflammation. Here, we investigated the effects of intraplantar (i.pl.) administration of functional N/OFQ and NOP receptor antagonists in a rat model of inflammatory pain. Our findings showed that i.pl. injection of (±)-J 113397, a selective antagonist of the NOP receptor, and NST, the functional N/OFQ antagonist, prior to carrageenan significantly reduced the paw allodynic and thermal hyperalgesic threshold induced by the inflammatory agent. The resulting antiallodynic and antihyperalgesic effects by co-administering NST and (±)-J 113397 prior to carrageenan were markedly enhanced, and the basal latencies were restored. Thus, it is likely that the peripheral N/OFQ/NOP receptor system contributes to the abnormal pain sensitivity in an inflammatory state.
authors: Department of Drug Sciences-Pharmacology and Toxicology Section, University of Catania, v.le A. Doria 6, 95125 Catania, Italy. scotog@unict.it
authors: Giovanna M
authors: GM
authors: Scoto
authors: Giuseppina
authors: G
authors: Aricò
authors: Simone
authors: S
authors: Ronsisvalle
authors: Carmela
authors: C
authors: Parenti
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006930:Hyperalgesia / Q000517:prevention & control; D007249:Inflammation / Q000503:physiopathology*; D007279:Injections, Subcutaneous; D008297:Male; D008684:Metatarsus; D009292:Narcotic Antagonists; D059226:Nociceptive Pain / Q000209:etiology / Q000517:prevention & control*; D018847:Opioid Peptides / Q000008:administration & dosage* / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D017288:Pain Threshold / Q000187:drug effects; D010525:Peripheral Nerves / Q000187:drug effects*; D010880:Piperidines / Q000008:administration & dosage* / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid; D015398:Signal Transduction / Q000187:drug effects; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D001562:Benzimidazoles; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010880:Piperidines; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C402921:J 113397; C111148:nocistatin; C000722285:Oprl1 protein, rat