ReviewNeurobiology of pain (Cambridge, Mass.)
Cyclic nucleotide signaling in sensory neuron hyperexcitability and chronic pain after nerve injury.
Review in Neurobiology of pain (Cambridge, Mass.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Gnao1 acts as a gatekeeper to alleviate neuropathic pain by silencing pro-nociceptive signaling cascades.The journal of headache and pain · 2026Article
- Activation and sensitization of meningeal nociceptors by PACAP-38: implications for migraine headache.Brain : a journal of neurology · 2026Article
- Integrated Multi-Omics Analyses Identify Acupuncture-Associated Changes in Gut Microbiota, Short-Chain Fatty Acids, and TNC Gene Expression in Chronic Migraine Rats.Journal of inflammation research · 2026Article
- HCN2 channels: a potential therapeutic target for orofacial neuropathic pain after trigeminal nerve injury.Journal of oral & facial pain and headache · 2026Article
- Efficacy of MEDI0618, a pH-dependent monoclonal antibody targeting PAR2, in preclinical models of migraine.Brain : a journal of neurology · 2025Article
- Action potential-independent spontaneous microdomain CaProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Targeting L-arginine/NO/cGMP/KFrontiers in pharmacology · 2025Review
- Ethnopharmacological Profile, Phytochemistry and Therapeutic Potential ofJournal of nutrition and metabolism · 2025Review
- Involvement of sphingosine-1-phosphate receptor 1 in pain insensitivity in a BTBR mouse model of autism spectrum disorder.BMC medicine · 2024Article
- Glial KCNQ KNeuron · 2024Article
- Article
- Axonal Regeneration: Underlying Molecular Mechanisms and Potential Therapeutic Targets.Biomedicines · 2022Review
- Obesity-Associated Neuropathy: Recent Preclinical Studies and Proposed Mechanisms.Antioxidants & redox signaling · 2022Review
- Blockage of HCN Channels Inhibits the Function of P2X Receptors in Rat Dorsal Root Ganglion Neurons.Neurochemical research · 2022Article
- The α isoform of cGMP-dependent protein kinase 1 (PKG1α) is expressed and functionally important in intrinsic primary afferent neurons of the guinea pig enteric nervous system.Neurogastroenterology and motility · 2021Article
- Article
- Inhibition of cAMP-phosphodiesterase 4 (PDE4) potentiates the anesthetic effects of Isoflurane in mice.Biochemical pharmacology · 2021Article
- Dorsal root ganglia NR2B-mediated Epac1-Piezo2 signaling pathway contributes to mechanical allodynia of bone cancer pain.Oncology letters · 2021Article
- Serotonin enhances depolarizing spontaneous fluctuations, excitability, and ongoing activity in isolated rat DRG neurons via 5-HTNeuropharmacology · 2021Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cyclic nucleotide signaling, including cAMP-PKA and cGMP-PKG pathways, has been well known to play critical roles in regulating cellular growth, metabolism and many other intracellular processes. In recent years, more and more studies have uncovered the roles of cAMP and cGMP in the nervous system. The cAMP and cGMP signaling mediates chronic pain induced by different forms of injury and stress. Here we summarize the roles of cAMP-PKA and cGMP-PKG signaling pathways in the pathogenesis of chronic pain after nerve injury. In addition, acute dissociation and chronic compression of the dorsal root ganglion (DRG) neurons, respectively, leads to neural hyperexcitability possibly through PAR2 activation-dependent activation of cAMP-PKA pathway. Clinically, radiotherapy can effectively alleviate bone cancer pain at least partly through inhibiting the cancer cell-induced activation of cAMP-PKA pathway. Roles of cyclic nucleotide signaling in neuropathic and inflammatory pain are also seen in many other animal models and are involved in many pro-nociceptive mechanisms including the activation of hyperpolarization-activated cyclic nucleotide (HCN)-modulated ion channels and the exchange proteins directly activated by cAMP (EPAC). Further understanding the roles of cAMP and cGMP signaling in the pathogenesis of chronic pain is theoretically significant and clinically valuable for treatment of chronic pain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.