Stimulation of sensory neuropeptide release by nociceptin/orphanin FQ leads to hyperaemia in acutely inflamed rat knees

Zhang, Chunfen; McDougall, Jason J.

doi:10.1038/sj.bjp.0706804

Cited by 22 publications

(13 citation statements)

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“…Tested under our experimental conditions, N/OFQ(1-13)NH 2 had no effect (0-120 min), or tended to increase the oedema volume after 120 min (the effect was not statistically significant). In this case, a probable explanation might be a secondary release of HA and other pro-inflammatory mediators by N/OFQ [14,15,17]. The lack of effect of pre-treatment with N/OFQ has also been reported by Sun et al [56] on bee venom-induced increase in paw volume.…”

Section: Oh) Formed With Omentioning

confidence: 79%

“…Based on the same mechanism, the peptide evokes vasodilation and macromolecular leak from mesenteric blood vessels [11]. In acute inflamed knee joints, a topic application of N/OFQ leads to a secondary release of pro-inflammatory mediators (NK-1, SP, CGRP, VIP) after activation of N/OFQ/orphanin peptide (NOP)-receptors on synovial mast cells and leukocytes [17]. Based on data obtained in their experiments on rat paw oedema, Nemeth et al concluded that chemically induced discharge of mediators from mast cells and from capsaicin-sensitive afferent nerve terminals were inhibited by nociceptin.…”

Section: Introductionmentioning

confidence: 99%

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In vivo effects of N/OFQ(1–13)NH2 and its structural analogue [ORN9]N/OFQ(1–13)NH2 on carrageenan-induced inflammation: rat-paw oedema and antioxidant status

et al. 2009

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Abstract:The effects of nociceptin(1-13)NH 2 (N/OFQ(1-13)NH 2 ) and its structural analogue [Orn 9 ]N/OFQ(1-13)NH 2 on acute carrageenan (CG)-induced peripheral inflammation and paw antioxidant status were studied. CG was injected intraplantarly in the right hind paw of rats and the volume of the inflamed paw was measured each 30 min for a period of 4h. When administered simultaneously with CG, N/OFQ(1-13)NH 2 decreased the paw volume, whereas if injected 15 min before CG it had no effect. [Orn 9 ]N/OFQ(1-13)NH 2 produced the opposite effects at the same time-intervals of its administration. We also investigated whether these neuropeptides influence CG-induced changes in cell antioxidant system, especially at the 4 th hour of CG administration. CG alone decreased the glutathione level and superoxide dismutase activity, as measured in post-nuclear homogenate of the inflamed paw. However, CG injection increased glutathione peroxidase and glucose-6-phospate dehydrogenase activities, while the activity of glutathione reductase was unchanged. The peptides themselves did not change all measured parameters. Moreover, neither N/OFQ(1-13)NH 2 nor [Orn 9 ]N/OFQ(1-13)NH 2 modified CG-induced changes in the antioxidant status, regardless of the time of their injection (simultaneously or 15 min before CG). The present results suggest that N/OFQ(1-13)NH 2 and [Orn 9 ]N/OFQ(1-13)NH 2 most likely affect the neuronal inflammation, rather than act as pro-or antioxidants.

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Section: Oh) Formed With Omentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

In vivo effects of N/OFQ(1–13)NH2 and its structural analogue [ORN9]N/OFQ(1–13)NH2 on carrageenan-induced inflammation: rat-paw oedema and antioxidant status

et al. 2009

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“…These immunocyte-derived factors can themselves cause joint inflammation and impart tissue hyperalgesia. For example, in acutely inflamed knees the vasomotor effect of N/OFQ is dependent on the presence of synovial mast cells and leucocytes [124], indicating a neuroimmune mode of action for this neuropeptide.…”

Section: Neuroimmune Pain Pathwaysmentioning

confidence: 99%

Untitled

McDougall

2006

Arthritis Res Ther

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225

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Arthritis pain affects millions of people worldwide yet we still have only a limited understanding of what makes our joints ache. This review examines the sensory innervation of diarthroidal joints and discusses the neurophysiological processes that lead to the generation of painful sensation. During inflammation, joint nerves become sensitized to mechanical stimuli through the actions of neuropeptides, eicosanoids, proteinase-activated receptors and ion channel ligands. The contribution of immunocytes to arthritis pain is also reviewed. Finally, the existence of an endogenous analgesic system in joints is considered and the reasons for its inability to control pain are postulated. IntroductionAccording to a recent report released by the World Health Organization [1], musculoskeletal disorders are the most frequent cause of disability in the modern world, and the prevalence of these diseases is rising at an alarming rate. The most prominent reason for loss of joint mobility and function is chronic or episodic pain, which leads to psychological distress and impaired quality of life. Current therapies to help alleviate joint pain have limited effectiveness and certain drugs produce unwanted negative side effects, thereby precluding their long-term use. In short, millions of patients are suffering from the debilitating effects of joint pain for which there is no satisfactory treatment. One of the reasons for this lack of effective pain management is the paucity in our knowledge of what actually causes joint pain. We are only now starting to identify some of the mediators and mechanisms that cause joints to become painful, allowing us to develop future new targets that could better alleviate arthritis pain. This review summarizes what is known about the origin of joint pain by describing the neurobiological processes initiated in the joint that give rise to neural signals and that are ultimately decoded by the central nervous system into pain perception. Joint innervation and nociceptionKnee joints are richly innervated by sensory and sympathetic nerves [2,3]. Postganglionic sympathetic fibres terminate near articular blood vessels, where they regulate joint blood flow through varying degrees of vasoconstrictor tone. The primary function of sensory nerves is to detect and transmit mechanical information from the joint to the central nervous system. Large diameter myelinated nerve fibres encode and transmit proprioceptive signals, which can be interpreted as being either dynamic (movement sensations) or static (position sense). Pain-sensing nerve fibres are typically less than 5 µm in diameter and are either unmyelinated (type IV) or myelinated with an unmyelinated 'free' nerve ending (type III). These slowly conducting fibres typically have a high threshold and only respond to noxious mechanical stimuli, and as such are referred to as nociceptors [4]. In the rat and cat, 80% of all knee joint afferent nerve fibres are nociceptive [5][6][7], suggesting that joints are astutely designed to sense abnormal and p...

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“…Behavioral arousal and alertness are prerequisites of the stress response. The Hcrt system sets the baseline of arousal and vigilant state under normal conditions, and also plays a critical role in stress responses and behavioral defense under threat situations (Kayaba et al, 2003;Zhang and McDougall, 2006). The involvement of Hcrt in the generation of SIA was first shown by Watanabe and his colleagues (Watanabe et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Direct inhibition of hypocretin/orexin neurons in the lateral hypothalamus by nociceptin/orphanin FQ blocks stress-induced analgesia in rats

2011

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We recently demonstrated that hypocretin/orexin (Hcrt) and nociceptin/orphanin FQ (N/OFQ) systems coordinately regulate nociception in a mouse model of stress-induced analgesia (SIA). However, the site of N/OFQ action on modulation of SIA was elusive, since N/OFQ was administered via intracerebroventricular (i.c.v.) injection acting on widely distributed N/OFQ receptors (NOP) in the brain. In the present study, we tested the hypothesis that N/OFQ modulates the SIA directly via the inhibition of the Hcrt neurons in the lateral hypothalamus. Using both fluorescent and electron microscopy, we found that N/OFQ-containing neurons are located in the lateral hypothalamus and the N/OFQ-containing fibers make direct contacts with the Hcrt neurons. Paw thermal nociceptive test revealed that the immobilization restraint of the rat increased the thermal pain threshold by 20.5±7.6%. Bilateral microinjection of N/OFQ (9 µg/side) into the rat perifornical area of the lateral hypothalamus, the brain area in which the Hcrt neurons are exclusively located, abolished the SIA. Activity of Hcrt neurons in the same animals was assessed using Fos immunohistochemistry. Percentage of Fos+/Hcrt neurons was lower in rats injected with N/OFQ than rats injected with saline, with the difference between groups stronger in the Hcrt neurons located medially to the fornix than in Hcrt neurons located laterally to the fornix. These results suggest that N/OFQ modulation of SIA is mediated by direct inhibition of Hcrt neuronal activity in the perifornical area. The uncovered peptidergic interaction circuitry may have broad implication in coordinated modulation by Hcrt and N/OFQ on other stress adaptive responses.

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Stimulation of sensory neuropeptide release by nociceptin/orphanin FQ leads to hyperaemia in acutely inflamed rat knees

Cited by 22 publications

References 51 publications

In vivo effects of N/OFQ(1–13)NH2 and its structural analogue [ORN9]N/OFQ(1–13)NH2 on carrageenan-induced inflammation: rat-paw oedema and antioxidant status

In vivo effects of N/OFQ(1–13)NH2 and its structural analogue [ORN9]N/OFQ(1–13)NH2 on carrageenan-induced inflammation: rat-paw oedema and antioxidant status

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Direct inhibition of hypocretin/orexin neurons in the lateral hypothalamus by nociceptin/orphanin FQ blocks stress-induced analgesia in rats

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