Peripheral anti-nociceptive effect of nociceptin/orphanin FQ in inflammation and stress-induced colonic hyperalgesia in rats.
Nociceptin/orphanin FQ (N/OFQ) and its NOP receptors are present in the central nervous system and in the periphery playing important roles in the modulation of gastrointestinal functions and pain. The aim of this study was to investigate the role of central and peripheral N/OFQ-NOP receptor system in the nociceptive response to colorectal distension (CRD) in basal condition and in two models of gut hypersensitivity triggered by both inflammation and stress. Male Wistar rats were tested in basal and in post-inflammatory conditions, i.e., 5 days after IC TNBS instillation (80 mg/Kg) and received N/OFQ (2 nmol/Kg IP), UFP-101 (a selective NOP receptor antagonist, 10 nmol/Kg IP), N/OFQ+UFP-101, N/OFQ (0.5 nmol/rat ICV) or vehicle. Female rats were tested in basal and after partial restraint stress receiving the same pharmacological treatment. CRD was performed using barostat and abdominal contractions were recorded by electromyography. In basal condition, N/OFQ, ICV and IP injected, did not modify basal visceral sensitivity. Both in TNBS and stress-induced hyperalgesia, IP but not ICV injection of N/OFQ significantly decreased the number of abdominal contractions. Peripheral injection of UFP-101 antagonized N/OFQ effect. Moreover, in post-inflammatory colitis, UFP-101, injected alone, exacerbated visceral hyperalgesia to CRD compared with vehicle. These findings indicate that in rats, N/OFQ, only peripherally injected, reduces visceral hypersensitivity triggered by inflammation or stress without affecting basal sensitivity. N/OFQ visceral anti-hyperalgesic effect involves peripheral NOP receptors. In a post-inflammatory, but not in an acute stress colitis model, N/OFQergic system is endogenously activated.
Agostini
Simona
S
INRA, EI-Purpan, UMR 1054 Neuro-Gastroenterology and Nutrition Unit, 180 Chemin de Tournefeuille - BP3, 31931 Toulouse Cedex 9, Toulouse, France Department of Human Physiology and Pharmacology, University La Sapienza, Rome, Italy.
Eutamene
Helene
H
Broccardo
Maria
M
Improta
Giovanna
G
Petrella
Carla
C
Theodorou
Vassillia
V
Bueno
Lionel
L
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D003092:Colitis / Q000188:drug therapy*; D003106:Colon / Q000294:innervation*; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D004347:Drug Interactions; D004576:Electromyography / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D018847:Opioid Peptides / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism; D012149:Restraint, Physical; D012684:Sensory Thresholds / Q000187:drug effects; D013315:Stress, Psychological / Q000150:complications; D014302:Trinitrobenzenesulfonic Acid; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000700:Analgesics; D018847:Opioid Peptides; D009195:Peroxidase; D011957:Receptors, Opioid; D014302:Trinitrobenzenesulfonic Acid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C479838:(Nphe(1),Arg(14),Lys(15))N-OFQ NH(2); C000722285:Oprl1 protein, rat