Janus kinase 2 activation participates in prostaglandin E2-induced hyperalgesia

Vieira, André Schwambach; Araldi, Dionéia; Dias, Elayne Vieira; Prado, Filipe César do; Tambeli, Cláudia Herrera; Parada, Carlos Amílcar

doi:10.1016/j.lfs.2016.10.001

Cited by 4 publications

(4 citation statements)

References 32 publications

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“…Interestingly, a recent report has demonstrated that PKCε is a merger point for the actions of PGE 2 and JAK2 [94]. Intrathecal injection of the JAK2-selective inhibitor AG490 blocked the membrane translocation of PKCε in the L5 DRG in a carrageenan-inflamed hind paw model [94]. The same administration also blunted the hyperalgesia induced by an intraplantar injection of PGE 2 or carrageenan [94].…”

Section: Kinase-mediated Ep Signal Transductionmentioning

confidence: 98%

“…Intrathecal injection of the JAK2-selective inhibitor AG490 blocked the membrane translocation of PKCε in the L5 DRG in a carrageenan-inflamed hind paw model [94]. The same administration also blunted the hyperalgesia induced by an intraplantar injection of PGE 2 or carrageenan [94]. Furthermore, they showed that an in vitro pre-incubation of DRG neurons with AG490 prevented the potentiation of a TRPV1mediated Ca 2+ influx by PGE 2 .…”

Section: Kinase-mediated Ep Signal Transductionmentioning

confidence: 99%

“…A JAK2-induced transcriptional cascade has been shown to be involved in inflammatory and neuropathic pain [92,93]. Interestingly, a recent report has demonstrated that PKCε is a merger point for the actions of PGE 2 and JAK2 [94]. Intrathecal injection of the JAK2-selective inhibitor AG490 blocked the membrane translocation of PKCε in the L5 DRG in a carrageenan-inflamed hind paw model [94].…”

Section: Kinase-mediated Ep Signal Transductionmentioning

confidence: 99%

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Molecular mechanisms underlying the actions of arachidonic acid-derived prostaglandins on peripheral nociception

Jang

Kim

Hwang

2020

J Neuroinflammation

163

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Arachidonic acid-derived prostaglandins not only contribute to the development of inflammation as intercellular pro-inflammatory mediators, but also promote the excitability of the peripheral somatosensory system, contributing to pain exacerbation. Peripheral tissues undergo many forms of diseases that are frequently accompanied by inflammation. The somatosensory nerves innervating the inflamed areas experience heightened excitability and generate and transmit pain signals. Extensive studies have been carried out to elucidate how prostaglandins play their roles for such signaling at the cellular and molecular levels. Here, we briefly summarize the roles of arachidonic acid-derived prostaglandins, focusing on four prostaglandins and one thromboxane, particularly in terms of their actions on afferent nociceptors. We discuss the biosynthesis of the prostaglandins, their specific action sites, the pathological alteration of the expression levels of related proteins, the neuronal outcomes of receptor stimulation, their correlation with behavioral nociception, and the pharmacological efficacy of their regulators. This overview will help to a better understanding of the pathological roles that prostaglandins play in the somatosensory system and to a finding of critical molecular contributors to normalizing pain.

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Section: Kinase-mediated Ep Signal Transductionmentioning

confidence: 98%

Section: Kinase-mediated Ep Signal Transductionmentioning

confidence: 99%

Section: Kinase-mediated Ep Signal Transductionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular mechanisms underlying the actions of arachidonic acid-derived prostaglandins on peripheral nociception

Jang

Kim

Hwang

2020

J Neuroinflammation

163

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“…[ 75 ] It would be of paramount significance to mention that JAK2 activation also plays a role in PGE2‐induced hyperalgesia. [ 76 ] Since PGE2 has a great influence on pain signals, [ 77 ] it can be the main cause of chest pain, abdominal pain, chest tightness, and myalgia as secondary and rare side effects of COVID‐19.…”

Section: Most Covid‐19 Symptoms Are In Relation With Pge2 Secretionmentioning

confidence: 99%

Why does COVID‐19 pathology have several clinical forms?

Aliabadi

Ajami

2020

BioEssays

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The outbreak of a new, potentially fatal virus, SARS-COV-2, which started in December 2019 in Wuhan, China, and since developed into a pandemic has stimulated research for an effective treatment and vaccine. For this research to be successful, it is necessary to understand the pathology of the virus. So far, we know that this virus can harm different organs of the body. Although the exact mechanisms are still unknown, this phenomenon may result from the body's secretion of prostaglandin E2 (PGE2), which is involved in several inflammation and immunity pathways. Noticeably, the expression of this molecule can lead to a cytokine storm causing a variety of side effects. In this paper, we discuss those side effects in SARS-COV-2 infection separately to determine whether PGE2 is, indeed, an important causative factor. Lastly, we propose a mechanism by which PGE2 production increases in response to COVID-19 disease and suggest the possible direct relation between PGE2 levels and the severity of this disease.

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Early response to JAK inhibitors on central sensitization and pain catastrophizing in patients with active rheumatoid arthritis

et al. 2022

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Objectives To evaluate the effect of 4 weeks of treatment with Janus kinase inhibitors (JAKis) on central sensitization (CS) and pain catastrophizing, and to determine the pain-related variables predictive of disease activity improvement, in patients with active rheumatoid arthritis (RA). Methods Consecutive RA patients with active disease starting a JAKi have been enrolled in this prospective observational study. Patients have been assessed at baseline and after 4 weeks of treatment. The evaluation was comprehensive of disease activity [Simplified Disease Activity Index (SDAI) and ultrasonographic (US) score] and of questionnaires aimed at investigating primarily CS [Central Sensitization Inventory (CSI)] and pain catastrophizing [Pain Catastrophizing Scale (PCS)]. Differences (Δ values) between the final and baseline were studied with the t test, Δ values of the variables were correlated with each other using Pearson’s test, and predictor variables for improvement in SDAI were also investigated using multivariate regression analysis. Results A total of 115 patients were evaluated. Overall, all variables demonstrated significant improvement between baseline and final except the US score. In particular, CSI decreased from 36.73 to 32.57 (p < 0.0001), PCS decreased from 32.46 to 28.72 (p = 0.0001). ΔSDAI showed a significant correlation with both ΔPCS and ΔCSI (r = 0.466 and 0.386, respectively, p < 0.0001). ΔPCS was the only variable predictive of an improvement in SDAI (coefficient = 0.500, p = 0.0224). Conclusion JAKis would appear to have a positive effect on pain-related variables, particularly CS and pain catastrophizing, for the genesis of which extra-synovial mechanisms are responsible.

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Janus kinase 2 activation participates in prostaglandin E2-induced hyperalgesia

Cited by 4 publications

References 32 publications

Molecular mechanisms underlying the actions of arachidonic acid-derived prostaglandins on peripheral nociception

Molecular mechanisms underlying the actions of arachidonic acid-derived prostaglandins on peripheral nociception

Why does COVID‐19 pathology have several clinical forms?

Early response to JAK inhibitors on central sensitization and pain catastrophizing in patients with active rheumatoid arthritis

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