Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162473 (Frey)
 2,599 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nociceptin, acting through the opioid receptor-like 1 (ORL1) receptor, produces anti-nociception in several models of neuropathy. We examined the involvement of the ORL1 receptor system in the allodynia developed after sciatic nerve ligation. Allodynic rats were selected by the von Frey hair and treated intrathecally with nociceptin or morphine. The peptide induced dose-dependent anti-allodynic activities, while morphine was effective at the higher dose only. By the semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay, the two described ORL1 receptor isoforms were up-regulated in the allodynic animals, but unmodified in non-allodynic rats. Both short and long ORL1 receptor mRNA isoforms increased in the ipsilateral lumbar enlargement (by 50% and 100%, respectively), while 50% and 60% increases were found in the ipsilateral L5-L6 dorsal root ganglia, respectively. No significant changes were observed for either the nociceptin precursor or mu-opioid receptor expression. Thus, the ORL1 receptor system seems to regulate the mechano-allodynia that developed after nerve damage, suggesting its potential role in the treatment of neuropathic pain.
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PMID:Up-regulation of ORL-1 receptors in spinal tissue of allodynic rats after sciatic nerve injury. 1210 3

The nociceptin system seems to be involved in modulation of acute nociceptive stimulation and in chronic pain processes, e.g. inflammation and neuropathy. In the present study, we examined the analgesic effect of a new opioid receptor-like (ORL1) receptor agonist, Ro64-6198, and compared it with the effect of endogenous ORL1 receptor agonist, nociceptin/orphanin FQ (N/OFQ), in a model of neuropathic pain in the rat. Ro64-6198 was injected intrathecaly (i.t.), intraplantarly (i.pl.) and subcutaneously (s.c.), and responses of neuropathic rats were measured in tactile (von Frey) and thermal (cold water) allodynia tests. Ro64-6198 did not change the pain threshold in naive animals, but exhibited antiallodynic activity in neuropathic rats. This effect was observed after i.t. and i.pl. but not after s.c. administration. Moreover, the observed antiallodynic potency of Ro64-6198 was weaker in comparison with N/OFQ after i.t. administration of either agonist, but almost equal after i.pl. injection. Selective antagonists of the ORL1 receptor, [Phe1Psi(CH2-NH)Gly2]NC(1-13)NH2 (PhePsi) and [N-Phe1]-NC(1-13)NH2 (NPhe), inhibited the antiallodynic actions of Ro64-6198 which indicated that the spinal and peripheral antinociceptive effects were mediated by ORL1 receptors. Therefore, besides spinal, also peripheral ORL1 receptors may be targeted by drugs designed for the long-term treatment of chronic pain.
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PMID:Spinal and local peripheral antiallodynic activity of Ro64-6198 in neuropathic pain in the rat. 1592 83

There has been a flurry of activity to develop agonists and antagonists for the member of the opioid receptor family, NOP receptor (also known as ORL1), in part to understand its role in pain. Modifications of a hexapeptide originally identified from a combinatorial library have led to the discovery of a high affinity hexapeptide agonist Ac-RY(3-Cl)YRWR-NH2 (Syn 1020). In the following experiments we characterized the anti-nociceptive effects of Syn 1020 in the tail-flick model of acute pain and the diabetic neuropathy model of chronic pain in mice and rats, respectively. Acute antinociception was assessed using the tail-flick assay in mice in which animals received intracerebroventricular (i.c.v.) or subcutaneous (s.c.) injections of Syn 1020 alone or with morphine and were tested for tail-flick latencies. In the chronic pain model, diabetic neuropathy was induced by injections of streptozotocin in rats. Tactile allodynia was measured, with von Frey hair filaments, following intraperitoneal (i.p.) injections of Syn 1020 or gabapentin (positive control). In mice, i.c.v. injections of Syn 1020 did not have any pro- or anti-nociceptive effects, however, Syn 1020 reversed morphine antinociception with a similar potency as N/OFQ (the natural ligand to NOP). S.c. injections of Syn 1020 in mice also produced analgesic effects. In rats, i.p, injections of Syn 1020 produced anti-allodynic effects. Thus, Syn 1020, a NOP receptor directed peptide, administered systemically has anti-nociceptive activity in both acute and chronic pain models in mice and rats respectively.
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PMID:Anti-nociceptive and anti-allodynic effects of a high affinity NOP hexapeptide [Ac-RY(3-Cl)YRWR-NH2] (Syn 1020) in rodents. 1730 10

Nociceptin/Orphanin FQ (N/OFQ) is a neuropeptide that modulates pain transmission, learning/memory, stress, anxiety, and fear responses via activation of the N/OFQ peptide (NOP or ORL1) receptor. Post-traumatic stress disorder (PTSD) is an anxiety disorder that may arise after exposure to a traumatic or fearful event, and often is co-morbid with chronic pain. Using an established animal model of PTSD, single-prolonged stress (SPS), we were the first to report that NOP receptor antagonist treatment reversed traumatic stress-induced allodynia, thermal hyperalgesia, and anxiety-like behaviors in male Sprague-Dawley rats. NOP antagonist treatment also reversed SPS-induced serum and CSF N/OFQ increase and circulating corticosterone decrease. The objective of this study was to examine the role of the NOP receptor in male and female rats subjected to traumatic stress using Wistar wild type (WT) and NOP receptor knockout (KO) rats. The severity of co-morbid allodynia was assessed as change in paw withdrawal threshold (PWT) to von Frey and paw withdrawal latency (PWL) to radiant heat stimuli, respectively. PWT and PWL decreased in male and female WT rats within 7 days after SPS, and remained decreased through day 28. Baseline sensitivity did not differ between genotypes. However, while male NOP receptor KO rats were protected from SPS-induced allodynia and thermal hypersensitivity, female NOP receptor KO rats exhibited tactile allodynia and thermal hypersensitivity to the same extent as WT rats. Male NOP receptor KO rats had a lower anxiety index (AI) than WT, but SPS did not increase AI in WT males. In contrast, SPS significantly increased AI in WT and NOP receptor KO female rats. SPS increased circulating N/OFQ levels in male WT, but not in male NOP receptor KO, or WT or KO female rats. These results indicate that the absence of the NOP receptor protects males from traumatic-stress-induced allodynia and hyperalgesia, consistent with our previous findings utilizing a NOP receptor antagonist. However, female NOP receptor KO rats experience allodynia, hyperalgesia and anxiety-like symptoms to the same extent as WT females following SPS. This suggests that endogenous N/OFQ-NOP receptor signaling plays an important, but distinct, role in males and females following exposure to traumatic stress.
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PMID:Sex Differences in Nociceptin/Orphanin FQ Peptide Receptor-Mediated Pain and Anxiety Symptoms in a Preclinical Model of Post-traumatic Stress Disorder. 3067 Sep 88