ArticleMolecular pain2012
Activation of extracellular signal-regulated protein kinase 5 is essential for cystitis- and nerve growth factor-induced calcitonin gene-related peptide expression in sensory neurons.
Article in Molecular pain, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 21 citations in OpenAlex.
- Pathophysiology and multi-target prevention strategies for cyclophosphamide-induced bladder injury.iScience · 2026Review
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- Association of neutrophil to high-density lipoprotein cholesterol ratio with overactive bladder: a population-based study.Frontiers in endocrinology · 2025Article
- Imatinib Mesylate Reduces Neurotrophic Factors and pERK and pAKT Expression in Urinary Bladder of Female Mice With Cyclophosphamide-Induced Cystitis.Frontiers in systems neuroscience · 2022Article
- Review
- Neuroimmune Mechanisms in Signaling of Pain During Acute Kidney Injury (AKI).Frontiers in medicine · 2020Review
- Drug Targets in Neurotrophin Signaling in the Central and Peripheral Nervous System.Molecular neurobiology · 2018Review
- Regulation of transient receptor potential cation channel subfamily V1 protein synthesis by the phosphoinositide 3-kinase/Akt pathway in colonic hypersensitivity.Experimental neurology · 2017Article
- Colitis-induced bladder afferent neuronal activation is regulated by BDNF through PLCγ pathway.Experimental neurology · 2016Article
- EXPRESS: Phospholipase C gamma mediates endogenous brain-derived neurotrophic factor - regulated calcitonin gene-related peptide expression in colitis - induced visceral pain.Molecular pain · 2016Article
- Treatment of painful bladder syndrome/interstitial cystitis with botulinum toxin A: why isn't it effective in all patients?Translational andrology and urology · 2015Review
- Local translation and retrograde axonal transport of CREB regulates IL-6-induced nociceptive plasticity.Molecular pain · 2014Article
- Neurotrophin signaling and visceral hypersensitivity.Frontiers in biology · 2014Article
- Endogenous PI3K/Akt and NMDAR act independently in the regulation of CREB activity in lumbosacral spinal cord in cystitis.Experimental neurology · 2013Article
- Calcitonin gene-related peptide stimulates BMP-2 expression and the differentiation of human osteoblast-like cells in vitro.Acta pharmacologica Sinica · 2013Article
- Article
- VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity.BMC physiology · 2012Article
- Early NGF-TrkA-CGRP signaling-related changes in dorsal root ganglia are associated with mechanical hypersensitivity in a zymosan A-induced SKG model prior to overt arthritis.Neurobiology of pain (Cambridge, Mass.)Article
- Research progress of the role and mechanism of extracellular signal-regulated protein kinase 5 (ERK5) pathway in pathological pain.Journal of Zhejiang University. Science. BReview
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCystitis causes considerable neuronal plasticity in the primary afferent pathways. The molecular mechanism and signal transduction underlying cross talk between the inflamed urinary bladder and sensory sensitization has not been investigated.
resultsIn a rat cystitis model induced by cyclophosphamide (CYP) for 48 h, the mRNA and protein levels of the excitatory neurotransmitter calcitonin gene-related peptide (CGRP) are increased in the L6 dorsal root ganglia (DRG) in response to bladder inflammation. Cystitis-induced CGRP expression in L6 DRG is triggered by endogenous nerve growth factor (NGF) because neutralization of NGF with a specific NGF antibody reverses CGRP up-regulation during cystitis. CGRP expression in the L6 DRG neurons is also enhanced by retrograde NGF signaling when NGF is applied to the nerve terminals of the ganglion-nerve two-compartmented preparation. Characterization of the signaling pathways in cystitis- or NGF-induced CGRP expression reveals that the activation (phosphorylation) of extracellular signal-regulated protein kinase (ERK)5 but not Akt is involved. In L6 DRG during cystitis, CGRP is co-localized with phospho-ERK5 but not phospho-Akt. NGF-evoked CGRP up-regulation is also blocked by inhibition of the MEK/ERK pathway with specific MEK inhibitors U0126 and PD98059, but not by inhibition of the PI3K/Akt pathway with inhibitor LY294002. Further examination shows that cystitis-induced cAMP-responsive element binding protein (CREB) activity is expressed in CGRP bladder afferent neurons and is co-localized with phospho-ERK5 but not phospho-Akt. Blockade of NGF action in vivo reduces the number of DRG neurons co-expressing CGRP and phospho-CREB, and reverses cystitis-induced increases in micturition frequency.
conclusionsA specific pathway involving NGF-ERK5-CREB axis plays an essential role in cystitis-induced sensory activation.
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