Involvement of the PKA pathway and inhibition of voltage gated Ca2+ channels in antihyperalgesic activity of Lippia grata/β-cyclodextrin

Siqueira-Lima, Pollyana S.; Quintans, Jullyana S.S.; Heimfarth, Luana; Passos, Fabíolla Rocha Santos; Pereira, Erik Willyame Menezes; Rezende, Marilia M.; Menezes-Filho, José Evaldo Rodrigues de; Barreto, Rosana S.S.; Coutinho, Henrique D.M.; Araújo, Adriano A. S.; Medrado, Aline S.; Naves, Ligia A.; Bomfim, Horácio Freitas; Lucchese, Angélica Maria; Gandhi, Sathiyabama Rajiv; Quintans‐Júnior, Lucindo J.

doi:10.1016/j.lfs.2019.116961

Cited by 4 publications

(1 citation statement)

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“…It transfers phosphate groups from ATP to serine or threonine residues of a specific protein for phosphorylation, and the phosphorylated proteins can regulate the activity of target proteins [10]. Studies have shown that PKA is closely related to inflammatory pain and bone cancer pain [11,12]. However, it is unclear whether PKA is involved in neuropathic pain caused by nerve damage.…”

Section: Introductionmentioning

confidence: 99%

Protein Kinase A Is Involved in Neuropathic Pain by Activating the p38MAPK Pathway to Mediate Spinal Cord Cell Apoptosis

Deng

Yang

Xie

et al. 2020

Mediators of Inflammation

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Neuropathic pain is a serious clinical problem to be solved. This study is aimed at investigating protein kinase A (PKA) expression in neuropathic pain and its possible mechanisms of involvement. A neuropathic pain-related gene expression dataset was downloaded from Gene Expression Omnibus, and differentially expressed genes were screened using the R software. cytoHubba was used to screen for hub genes. A spared nerve injury (SNI) rat model was established, and the paw withdrawal threshold was determined using von Frey filaments. Western blotting and immunofluorescence were used to detect the expression and cellular localization, respectively, of key proteins in the spinal cord. Western blot, ELISA, and TUNEL assays were used to detect cell signal transduction, inflammation, and apoptosis, respectively. Pka was identified as a key gene involved in neuropathic pain. After SNI, mechanical allodynia occurred, PKA expression in the spinal cord increased, the p38MAPK pathway was activated, and spinal cord inflammation and apoptosis occurred in rats. PKA colocalized with neurons, astrocytes, and microglia, and apoptotic cells were mainly neurons. Intrathecal injection of a PKA inhibitor not only relieved mechanical hyperalgesia, inflammatory reaction, and apoptosis in SNI rats but also inhibited p38MAPK pathway activation. However, intrathecal injection of a p38MAPK inhibitor attenuated mechanical hyperalgesia, inflammation, and apoptosis, but did not affect PKA expression. In conclusion, PKA is involved in neuropathic pain by activating the p38MAPK pathway to mediate spinal cord cell apoptosis.

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Section: Introductionmentioning

confidence: 99%