Acute and persistent nociceptive paw sensitisation in mice: The involvement of distinct signalling pathways

Villarreal, Cristiane Flora; Funez, Mani Indiana; Figueiredo, Florêncio; Cunha, Fernando; Parada, Carlos Amílcar; Ferreira, Sérgio Henrique

doi:10.1016/j.lfs.2009.10.018

Cited by 35 publications

(33 citation statements)

References 58 publications

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“…Studies using a model of persistent inflammatory sensitisation in rats and mice show that PKA could exert a role in the maintenance of the chronic state. The persistent sensitisation is abolished by injection of PKA inhibitors, and PKA expression and activity were up-regulated in DRG (Villarreal et al, 2009a(Villarreal et al, , 2009b. The contribution of PKA to sensitisation maintenance seems to be due to the regulation of the Na v 1.8 sodium channel expression (Villarreal et al, 2009a).…”

Section: Pkamentioning

confidence: 93%

“…Studies suggest that PKC activity in the DRG is up-regulated by and is at least partially responsible for the persistent condition, as shown by analyses of PKC activity in rat DRGs (Villarreal et al 2009a). Moreover, the local administration of a selective PKC inhibitor abolished the persistent state induced by PGE 2 in rats and mice (Villarreal et al 2009a;Villarreal et al, 2009b). Evaluation of the mechanisms downstream of PKC activation found that Na v 1.8 mRNA levels in the DRG from rats was up-regulated and inhibition of PKC activity reduced these levels (Villarreal et al, 2009a).…”

Section: Pkcmentioning

confidence: 99%

“…Inflammatory sensitisation has a "sympathetic" component that involves the release of amines such as epinephrine and dopamine (Coderre et al 1984;Nakamura and Ferreira 1987). Evidence suggests that mechanical sensitisation induced either by epinephrine in rats (Khasar et al 1999b) or dopamine in mice (Villarreal et al, 2009b) is blocked by PKCε-selective inhibition. Cesare et al (1999) found that bradykinin exposure induces PKCε translocation from the cytosol to a membrane-associated position in cultured DRG neurons, thus contributing to heat sensitisation.…”

Section: Pkcmentioning

confidence: 99%

“…Mechanical persistent inflammatory sensitisation can also be induced by intraplantar administration of inflammatory mediators like prostaglandins and sympathetic amines in rats and mice Villarreal et al, 2009b). Studies suggest that PKC activity in the DRG is up-regulated by and is at least partially responsible for the persistent condition, as shown by analyses of PKC activity in rat DRGs (Villarreal et al 2009a).…”

Section: Pkcmentioning

confidence: 99%

“…Since this original study, many subsequent studies have shown that cAMP generation is induced by a plethora of inflammatory stimuli. The mechanical nociceptor sensitisation that occurs during inflammation or induced by either inflammatory mediators (PGE 2 , dopamine, serotonin) is blocked by treatment with PKA inhibitors in rats and mice (Taiwo and Levine 1991;Taiwo et al, 1992;Aley and Levine, 1999;Aley et al, 2000;Sachs et al, 2009;Villarreal et al, 2009b).…”

Section: Pkamentioning

confidence: 99%

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Section: Pkamentioning

confidence: 93%

Section: Pkcmentioning

confidence: 99%

Section: Pkcmentioning

confidence: 99%

Section: Pkcmentioning

confidence: 99%

Section: Pkamentioning

confidence: 99%

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G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub

Penela

Ribas

Sánchez-Madrid

et al. 2019

Cell. Mol. Life Sci.

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Accumulating evidence indicates that G protein-coupled receptor kinase 2 (GRK2) is a versatile protein that acts as a signaling hub by modulating G protein-coupled receptor (GPCR) signaling and also via phosphorylation or scaffolding interactions with an extensive number of non-GPCR cellular partners. GRK2 multifunctionality arises from its multidomain structure and from complex mechanisms of regulation of its expression levels, activity, and localization within the cell, what allows the precise spatio-temporal shaping of GRK2 targets. A better understanding of the GRK2 interactome and its modulation mechanisms is helping to identify the GRK2-interacting proteins and its substrates involved in the participation of this kinase in different cellular processes and pathophysiological contexts.

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Carvacrol attenuates mechanical hypernociception and inflammatory response

Guimarães

Xavier

Santana

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

151

104

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Carvacrol is a phenolic monoterpene present in the essential oil of the family Lamiaceae, as in the genera Origanum and Thymus. We previously reported that carvacrol is effective as an analgesic compound in various nociceptive models, probably by inhibition of peripheral mediators that could be related with its strong antioxidant effect observed in vitro. In this study, the anti-hypernociceptive activity of carvacrol was tested in mice through models of mechanical hypernociception induced by carrageenan, and the involvement of important mediators of its signaling cascade, as tumor necrosis factor-alpha (TNF-α), prostaglandin E(2) (PGE(2)), and dopamine, were assessed. We also investigated the anti-inflammatory effect of carvacrol on the model of carrageenan-induced pleurisy and mouse paw edema, and the lipopolysaccharide (LPS)-induced nitrite production in murine macrophages was observed. Systemic pretreatment with carvacrol (50 or 100 mg/kg; i.p.) inhibited the development of mechanical hypernociception and edema induced by carrageenan and TNF-α; however, no effect was observed on hypernociception induced by PGE(2) and dopamine. Besides this, carvacrol significantly decreased TNF-α levels in pleural lavage and suppressed the recruitment of leukocytes without altering the morphological profile of these cells. Carvacrol (1, 10, and 100 μg/mL) also significantly reduced (p < 0.001) the LPS-induced nitrite production in vitro and did not produce citotoxicity in the murine peritoneal macrophages in vitro. The spontaneous locomotor activity of mice was not affected by carvacrol. This study adds information about the beneficial effects of carvacrol on mechanical hypernociception and inflammation. It also indicates that this monoterpene might be potentially interesting in the development of novel tools for management and/or treatment of painful conditions, including those related to inflammatory and prooxidant states.

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Acute and persistent nociceptive paw sensitisation in mice: The involvement of distinct signalling pathways

Cited by 35 publications

References 58 publications

Protein Kinases and Pain

Protein Kinases and Pain

G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub

Carvacrol attenuates mechanical hypernociception and inflammatory response

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