Capsaicin-sensitive sensory nerves exert complex regulatory functions in the serum-transfer mouse model of autoimmune arthritis

Borbély, Éva; Botz, Bálint; Bölcskei, Kata; Kenyér, Tibor; Kereskai, László; Kiss, Tamás; Szolcsányi, Janós; Pintér, Erika; Csepregi, Janka Zsófia; Mócsai, Attila; Helyes, Zsuzsanna

doi:10.1016/j.bbi.2014.12.012

Cited by 56 publications

(61 citation statements)

References 56 publications

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“…The unique features of SzV-1287 compared to other SSAO inhibitors are its COX inhibitory action, without ulcerogenic effects25, and potent dual antagonistic property at the TRPV1/TRPA1 ion channels localised on peptidergic sensory nerves39, inflammatory cells40, and chondrocytes4142. The importance of TRPV1/TRPA1-dependent neurogenic inflammatory mechanisms in RA has been extensively investigated and received a great attention434445. Both receptors are a ligand-gated cation channel activated by various inflammatory mediators including protons, lipids, reactive oxygen species and lipoxygenase products, which result in the release of a broad range of neuropeptides40.…”

Section: Discussionmentioning

confidence: 99%

Analgesic and Anti-Inflammatory Effects of the Novel Semicarbazide-Sensitive Amine-Oxidase Inhibitor SzV-1287 in Chronic Arthritis Models of the Mouse

Horváth

Menghis

Botz

et al. 2017

Sci Rep

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Semicarbazide-sensitive amine oxidase (SSAO) catalyses oxidative deamination of primary amines. Since there is no data about its function in pain and arthritis mechanisms, we investigated the effects of our novel SSAO inhibitor SzV-1287 in chronic mouse models of joint inflammation. Effects of SzV-1287 (20 mg/kg i.p./day) were investigated in the K/BxN serum-transfer and complete Freund’s adjuvant (CFA)-evoked active immunization models compared to the reference SSAO inhibitor LJP-1207. Mechanonociception was assessed by aesthesiometry, oedema by plethysmometry, clinical severity by scoring, joint function by grid test, myeloperoxidase activity by luminescence, vascular leakage by fluorescence in vivo imaging, histopathological changes by semiquantitative evaluation, and cytokines by Luminex assay. SzV-1287 significantly inhibited hyperalgesia and oedema in both models. Plasma leakage and keratinocyte chemoattractant production in the tibiotarsal joint, but not myeloperoxidase activity was significantly reduced by SzV-1287 in K/BxN-arthritis. SzV-1287 did not influence vascular and cellular mechanisms in CFA-arthritis, but significantly decreased histopathological alterations. There was no difference in the anti-hyperalgesic and anti-inflammatory actions of SzV-1287 and LJP-1207, but only SzV-1287 decreased CFA-induced tissue damage. Unlike SzV-1287, LJP-1207 induced cartilage destruction, which was confirmed in vitro. SzV-1287 exerts potent analgesic and anti-inflammatory actions in chronic arthritis models of distinct mechanisms, without inducing cartilage damage.

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Section: Discussionmentioning

confidence: 99%

Analgesic and Anti-Inflammatory Effects of the Novel Semicarbazide-Sensitive Amine-Oxidase Inhibitor SzV-1287 in Chronic Arthritis Models of the Mouse

Horváth

Menghis

Botz

et al. 2017

Sci Rep

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“…In mBSA antigen-induced arthritis (AIA), the initial steps of joint inflammation are abrogated when IL-6 signal transducer is knocked out of Na v 1.8-positive nociceptor neurons [92]. By contrast, removal of TRPV1-positive nociceptor neurons by pre-treatment with resiniferatoxin (RTX) exacerbates joint inflammation in the K/BxN arthritis model [93] (Figure 4b). This could be due to differences in animal models as well as the role of specific nociceptor subtypes targeted in these studies.…”

Section: Nociceptor Neuron Regulation Of Inflammation and Immunitymentioning

confidence: 99%

Nociceptor Sensory Neuron–Immune Interactions in Pain and Inflammation

Pinho‐Ribeiro

Verri

Chiu

2017

Trends in Immunology

746

626

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Nociceptor sensory neurons protect organisms from dangers by eliciting pain and driving avoidance. Pain also accompanies many types of inflammation and injury. It is increasingly clear that active crosstalk occurs between nociceptor neurons and the immune system to regulate pain, host defense, and inflammatory diseases. Immune cells at peripheral nerve terminals and within the spinal cord release mediators that modulate mechanical and thermal sensitivity. In turn, nociceptor neurons release neuropeptides and neurotransmitters from nerve terminals that regulate vascular, innate, and adaptive immune cell responses. Therefore, the dialogue between nociceptor neurons and the immune system is a fundamental aspect of inflammation, both acute and chronic. A better understanding of these interactions could produce approaches to treat chronic pain and inflammatory diseases.

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“…Sympathetic and TRPV1 + sensory neurons exert pro-inflammatory activity during disease initiation, while established RA results in a loss of immunomodulatory sympathetic fibers and outgrowth of sensory innervation, which may contribute to disease chronicity [236–242]. …”

Section: Neuro-immune Interactions During Infection and Diseasementioning

confidence: 99%

The Regulation of Immunological Processes by Peripheral Neurons in Homeostasis and Disease

Ordovás-Montañés

Rakoff-Nahoum

Huang

et al. 2015

Trends in Immunology

149

123

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The nervous system and the immune system are the principal sensory interfaces between the internal and external environment. They are responsible for recognizing, integrating, and responding to varied stimuli, and have the capacity to form memories of these encounters leading to learned or ‘adaptive’ future responses. Here, we review the current understanding of the cross-regulation between these systems. The autonomic and somatosensory nervous systems regulate both the development and deployment of immune cells, with broad functions that impact hematopoiesis as well as priming, migration and cytokine production. In turn, specific immune cell subsets contribute to homeostatic neural circuits such as those controlling metabolism, hypertension and the inflammatory reflex. We examine the contribution of the somatosensory system to autoimmune, autoinflammatory, allergic, and infectious processes in barrier tissues and in this context, discuss opportunities for therapeutic manipulation of neuro-immune interactions.

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Capsaicin-sensitive sensory nerves exert complex regulatory functions in the serum-transfer mouse model of autoimmune arthritis

Cited by 56 publications

References 56 publications

Analgesic and Anti-Inflammatory Effects of the Novel Semicarbazide-Sensitive Amine-Oxidase Inhibitor SzV-1287 in Chronic Arthritis Models of the Mouse

Analgesic and Anti-Inflammatory Effects of the Novel Semicarbazide-Sensitive Amine-Oxidase Inhibitor SzV-1287 in Chronic Arthritis Models of the Mouse

Nociceptor Sensory Neuron–Immune Interactions in Pain and Inflammation

The Regulation of Immunological Processes by Peripheral Neurons in Homeostasis and Disease

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