Abstract
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.
Highlights
Neuropathic pain is a chronic pain state caused by primary damage or dysfunction of the nervous system [1]
We downloaded a neuropathic painrelated gene expression dataset from the Gene Expression Omnibus (GEO) database [9], and we identified differentially expressed genes (DEGs) using the R software
We hypothesized that protein kinase A (PKA) is involved in neuropathic pain by activating the p38MAPK pathway to mediate spinal cord cell apoptosis
Summary
Neuropathic pain is a chronic pain state caused by primary damage or dysfunction of the nervous system [1]. Neuropathic pain is a severely debilitating state that seriously affects the quality of life of patients [3]. Numerous in-depth studies have been conducted on neuropathic pain, its pathogenesis has not yet been fully elucidated. Recent evidence suggests that the generation of neuropathic pain is related to changes in pain-related expression of genes such as COMT, TRPV1, MC1R, GCH1, and CACNA2D3 [4]. Studies have shown that herpes simplex virus vector-mediated TNF-α receptor expression significantly attenuated neuropathic pain [5, 6]. Studying gene expression is important for elucidating the molecular mechanisms of neuropathic pain and discovering potential therapeutic targets
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