Peripheral anti-nociceptive effect of nociceptin/orphanin FQ in inflammation and stress-induced colonic hyperalgesia in rats

Abstract

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.

Genotype-dependent responsivity to inflammatory pain: A role for TRPV1 in the periaqueductal grey

“…It is expressed in peripheral tissues (intestine, vas deferens, spleen and immune system) and also in the central nervous system (cortical brain areas, olfactory regions, hippocampus, amygdala and thalamus) (Tariq et al, 2013). A role for the NOP receptor has been demonstrated in peripherally mediated stress-induced hyperalgesia (Agostini et al, 2009) and further studies are required to decipher its role within the CNS in pain and stress interactions.…”

Expression of the nociceptin/orphanin FQ receptor in the intestinal mucosa of IBS patients

“…N/OFQ and the NOP receptor are present in the central nervous system (CNS) and in the periphery, playing important roles in the modulation of gastrointestinal function and pain (13). To assess whether the NOP receptor is involved in the pathogeneses of IBS, we measured the levels of NOP receptor mRNA and protein in the jejunal and colonic tissues of healthy subjects and of patients with D-IBS and C-IBS.…”

Nociceptin Inhibits Uterine Contractions in Term-Pregnant Rats by Signaling Through Multiple Pathways1

“…Sensory neuropeptides (e.g., tachykinin, calcitonin gene-related peptide, and galanin), released in an efferent fashion from sensory nerve endings, regulate uterine contractility and also play important roles in the mediation of peripheral nociception [15,18,19]. Previous results on the role of PNOC in central and peripheral pain processing [4,32] aroused our interest regarding its participation in the modulation of uterine contractions of the latepregnant rat.…”