Cyclic nucleotide signaling in sensory neuron hyperexcitability and chronic pain after nerve injury

Li, Ze-Hua; Cui, Dong; Qiu, Chengjie; Song, Xue-Jun

doi:10.1016/j.ynpai.2019.100028

Cited by 34 publications

(27 citation statements)

References 196 publications

(272 reference statements)

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“…Signaling by cAMP-PKA has been well established as a driver of sensory neuron sensitization (Bavencoffe et al, 2016, Efendiev et al, 2013, Li et al, 2019, Song et al, 2006, Villarreal et al, 2009). Much less is known about the roles of another downstream effector, EPAC (Hucho and Levine, 2007).…”

Section: Discussionmentioning

confidence: 99%

EPAC1 and EPAC2 promote nociceptor hyperactivity associated with chronic pain after spinal cord injury

Berkey

Herrera

Odem

et al. 2020

Neurobiology of Pain

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Chronic pain following spinal cord injury (SCI) is associated with electrical hyperactivity (spontaneous and evoked) in primary nociceptors. Cyclic adenosine monophosphate (cAMP) signaling is an important contributor to nociceptor excitability, and knockdown of the cAMP effector, exchange protein activated by cAMP (EPAC), has been shown to relieve pain-like responses in several chronic pain models. To examine potentially distinct roles of each EPAC isoform (EPAC1 and 2) in maintaining chronic pain, we used rat and mouse models of contusive spinal cord injury (SCI). Pharmacological inhibition of EPAC1 or 2 in a rat SCI model was sufficient to reverse SCI-induced nociceptor hyperactivity, indicating that EPAC1 and 2 signaling activity are complementary, with both required to maintain hyperactivity. However, EPAC activation was not sufficient to induce similar hyperactivity in nociceptors from naïve rats, and we observed no change in EPAC protein expression after SCI. In the mouse SCI model, inhibition of both EPAC isoforms through a combination of pharmacological inhibition and genetic deletion was required to reverse SCI-induced nociceptor hyperactivity. This was consistent with our finding that neither EPAC1−/− nor EPAC2−/− mice were protected against SCI-induced chronic pain as assessed with an operant mechanical conflict test. Thus, EPAC1 and 2 activity may play a redundant role in mouse nociceptors, although no corresponding change in EPAC protein expression levels was detected after SCI. Despite some differences between these species, our data demonstrate a fundamental role for both EPAC1 and EPAC2 in mechanisms maintaining nociceptor hyperactivity and chronic pain after SCI.

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Section: Discussionmentioning

confidence: 99%

EPAC1 and EPAC2 promote nociceptor hyperactivity associated with chronic pain after spinal cord injury

Berkey

Herrera

Odem

et al. 2020

Neurobiology of Pain

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show abstract

“…Hence, treatments targeting the PI3K-Akt signaling pathway provide a promising approach to prevent ESCA and/or to slow its progression. The cGMP-PKG signaling pathway modulates massive physiological and pathological parameters [ 35 ]. Correlation between inflammation and the cGMP-PKG signaling pathway has been identified, involving mechanisms of neutrophil migration, mitochondrial permeability transition, and oscillations of calcium ions [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of Hub Genes and Pathways In Esophageal Carcinoma Based on NCBI’s Gene Expression Omnibus (GEO) Database: A Bioinformatics Analysis

Yu-Jing

Tang

2020

Med Sci Monit

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Background Esophageal carcinoma (ESCA) is a health challenge with poor prognosis and limited treatment options. Our aim is to screen for hub genes and pathways associated with ESCA pathology as diagnostic or therapeutic targets. Material/Methods We downloaded 2 ESCA-related datasets from the Gene Expression Omnibus (GEO) database. Subsequently, differentially expressed genes (DEGs) of ESCA were determined by statistical analysis. Both Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed using online analytic tools. Network analysis was employed to construct a protein-protein interaction (PPI) network and to filter hub genes. We evaluated the expression level and impact of hub genes on survival of ESCA patients using the OncoLoc webserver. Results A total of 210 DEGs were identified. The GO analysis showed that the DEGs were enriched in cell division. The KEGG pathway analysis showed DEGs that were enriched in cell cycle regulation, known cancer pathways, the PI3K-Akt signaling pathway, and the cGMP-PKG signaling pathway. The top 10 hub genes were markedly upregulated in ESCA tissue compared with normal esophageal tissue. Moreover, the expression level of the hub genes was different at different pathological stages of ESCA. Further prognostic analysis identified that the top 10 hub genes were related to late survival of ESCA patients, while exhibiting few associations with early survival time. Conclusions The signaling pathways involving the DEGs probably represent the pathological mechanism underlying ESCA. The hub genes were associated with survival of ESCA patients, and as such have the potential to serve as diagnostic indicators and therapeutic targets.

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“…The role of cGMP/PKG signaling in neuropathic and inflammatory pain has also been observed in many other animal models, and it involves many mechanisms of ACTH. 30 Through the no/cGMP/PKG/…”

Section: Dovepressmentioning

confidence: 99%

<p>ATAS Acupuncture Reduces Chemotherapy Induced Fatigue in Breast Cancer Through Regulating ADROA1 Expression: A Randomized Sham-Controlled Pilot Trial</p>

Li¹,

Liu²,

Nie³

et al. 2020

OTT

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Cyclic nucleotide signaling in sensory neuron hyperexcitability and chronic pain after nerve injury

Abstract: Highlights Activation of cAMP-PKA and cGMP-PKG pathways contributes to injury-induced sensory neuron hyperexcitability. Activation of cAMP and cGMP contributes to the development of bone cancer pain. PAR2 activation mediates injury-induced cAMP-dependent sensory neuron hyperexcitability.

Cited by 34 publications

References 196 publications

EPAC1 and EPAC2 promote nociceptor hyperactivity associated with chronic pain after spinal cord injury

EPAC1 and EPAC2 promote nociceptor hyperactivity associated with chronic pain after spinal cord injury

Integrated Analysis of Hub Genes and Pathways In Esophageal Carcinoma Based on NCBI’s Gene Expression Omnibus (GEO) Database: A Bioinformatics Analysis

<p>ATAS Acupuncture Reduces Chemotherapy Induced Fatigue in Breast Cancer Through Regulating ADROA1 Expression: A Randomized Sham-Controlled Pilot Trial</p>

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