Neuronal P2X3 receptor activation is essential to the hyperalgesia induced by prostaglandins and sympathomimetic amines released during inflammation

Prado, Filipe César do; Araldi, Dionéia; Vieira, A.S.; Oliveira, Maria Cláudia G.; Tambeli, Cláudia Herrera; Parada, Carlos A.

doi:10.1016/j.neuropharm.2012.11.011

Cited by 59 publications

(45 citation statements)

References 42 publications

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“…During the inflammatory process in peripheral tissue, neither prostaglandins nor sympathetic amines can sensitize primary afferent neurons by themselves; they depend on previous neuronal P2X3 receptor activation [103]. Spontaneous and evoked responses of spinal nociceptive neurons are attenuated by P2X3 receptor antagonism in inflamed rats [104].…”

Section: Inflammatory Painmentioning

confidence: 99%

P2X ion channel receptors and inflammation

Burnstock

2016

Purinergic Signalling

184

153

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Neuroinflammation limits tissue damage in response to pathogens or injury and promotes repair. There are two stages of inflammation, initiation and resolution. P2X receptors are gaining attention in relation to immunology and inflammation. The P2X7 receptor in particular appears to be an essential immunomodulatory receptor, although P2X1 and P2X4 receptors also appear to be involved. ATP released from damaged or infected cells causes inflammation by release of inflammatory cytokines via P2X7 receptors and acts as a danger signal by occupying upregulated P2X receptors on immune cells to increase immune responses. The purinergic involvement in inflammation is being explored for the development of novel therapeutic strategies.

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Section: Inflammatory Painmentioning

confidence: 99%

P2X ion channel receptors and inflammation

Burnstock

2016

Purinergic Signalling

184

153

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“…Clinically the P2X7 receptor antagonists CE-224535 and AZD9056 have not demonstrated efficacy in rheumatoid arthritis and it is unknown whether they may be useful in pain indications [45,46]. P2X3 receptor expression changes in animal pain models of P2X3 knock-out mice have shown the development of reduced mechanical allodynia [47] and neuronal P2X3 receptor activation predisposing afferent neurons to inflammatory hyperalgesia [48]. The antitussive actions of the P2X3 antagonist AF-219 occurs in the absence of any effect on capsaicin-induced cough [49], which is consistent with preclinical cough studies in guinea pigs showing that ATP and capsaicin have independent mechanisms of action [50].…”

Section: Introductionmentioning

confidence: 99%

An update and systematic review on drug therapies for the treatment of refractory chronic cough

Ryan

Vertigan

Birring

2018

Expert Opinion on Pharmacotherapy

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Introduction: Chronic Cough (CC) is common and often associated with significant comorbidity and decreased quality of life. In up to 50% of cases, the cough is refractory despite extensive investigation and treatment trials. It is likely that the key abnormality in refractory CC is dysfunctional, hypersensitive sensory nerves, similar to conditions such as laryngeal hypersensitivity and neuropathic pain.Areas covered: The aim of this systematic review is to assess drug therapies for refractory CC. The authors review the current management of CC and provide discussion of the similarities between neuropathic pain and refractory CC. They review repurposed and new pharmacological treatments. Several meta-analyses were performed to compare the efficacy of treatments where possible.Expert opinion: Repurposed pain medications such as gabapentin and pregabalin reduce the frequency of cough and improve quality of life. Along with speech pathology, they are important and alternate treatments for refractory CC. However, more treatments are needed and the P2X3 ion channel receptor antagonists show the most promise. With a better understanding of neuronal activation and sensitisation and their signal processing in the brain, improved animal models of cough, and the use of validated cough measurement tools, more effective treatments will develop.

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“…The edema induced is mediated by histamine and 5HT during the 1st hour after which the increased vascular permeability is maintained by kinin release up to 2.5 hours. Thereafter up to 6 hours the mediator appears to be prostaglandins 28 , release of which is closely associated with migration of leucocytes into the inflamed site. All the mediators appear to be dependent upon an intact complement system for their activation and release 29 .…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Activity of H1 Receptor Antagonist Cetirizine in Animal Models

S.H¹,

Santoshkumar²

2013

jemds

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AIM:The present study was designed to study anti-inflammatory activity of Cetirizine in albino rats and compare with standard drug Diclofenac. MATERIAL & METHODS: 1. Carrageenin induced rat paw edema method (Acute inflammation): 5 animals in each group (3groups) received orally 4% Gum acacia, Diclofenac sodium and Cetirizine respectively one hour before carrageenin injection into right paw. The rat paw edema was measured with plethysmograph after 3 hours and percentage inhibition of edema was calculated in each group. 2. Rexin pellet granuloma method (Chronic inflammation): Four rexin pellets were implanted into dorsum skin of each rat of 3 groups (n=5), which include control, Diclofenac and Cetirizine respectively. The animals were treated with fixed doses of drugs once a day for 7 days including the day of implantation of pellets and on 8th day rexin pellets were removed after sacrificing animals. Rexin pellets were kept in incubator at 60 0 C overnight. Pellets were then weighed and percent inhibition of granuloma tissue was calculated. 3. Study of Mast cell counts. RESULT: Cetirizine showed significant anti-inflammatory activity both in acute and chronic animal models. CONCLUSION: Cetirizine may be used as potential drug for both acute and chronic inflammation due to its anti-inflammatory property.

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Neuronal P2X3 receptor activation is essential to the hyperalgesia induced by prostaglandins and sympathomimetic amines released during inflammation

Cited by 59 publications

References 42 publications

P2X ion channel receptors and inflammation

P2X ion channel receptors and inflammation

An update and systematic review on drug therapies for the treatment of refractory chronic cough

Anti-Inflammatory Activity of H1 Receptor Antagonist Cetirizine in Animal Models

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