ArticleNeurobiology of pain (Cambridge, Mass.)
EPAC1 and EPAC2 promote nociceptor hyperactivity associated with chronic pain after spinal cord injury.
Article 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 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Inhibition of adenylyl cyclase 1 or exchange protein activated by cAMP restores ATP-sensitive potassium channel activity after chronic opioid exposure.British journal of pharmacology · 2026Article
- C-C motif chemokine ligand 12 (CCL12) is a critical chemokine driving postoperative pain.Pain · 2026Article
- Targeting molecular pathways in neuropathic cancer pain: from mechanisms to novel therapeutics.iScience · 2026Review
- The Increased Activity of CaV3.2 Channels Contributes to Nociceptors' Hyperexcitability and Chronic Neuropathic Pain Following Spinal Cord Injury in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Unbiased quantification of persistent postural and motor deficits following spinal cord injury in mice.PloS one · 2026Article
- Article
- Maladaptive changes in the homeostasis of AEA-TRPV1/CB1R induces pain-related hyperactivity of nociceptors after spinal cord injury.Cell & bioscience · 2025Article
- B cells drive neuropathic pain-related behaviors in mice through IgG-Fc gamma receptor signaling.Science translational medicine · 2024Article
- Mechanism of gabapentinoid potentiation of opioid effects on cyclic AMP signaling in neuropathic pain.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Induction of long-term hyperexcitability by memory-related cAMP signaling in isolated nociceptor cell bodies.bioRxiv : the preprint server for biology · 2024Article
- Chemogenetic Attenuation of Acute Nociceptive Signaling Enhances Functional Outcomes Following Spinal Cord Injury.Journal of neurotrauma · 2024Article
- Role of EPAC1 in chronic pain.Biochemistry and biophysics reports · 2024Review
- Widespread latent hyperactivity of nociceptors outlasts enhanced avoidance behavior following incision injury.bioRxiv : the preprint server for biology · 2024Article
- Persistent nociceptor hyperactivity as a painful evolutionary adaptation.Trends in neurosciences · 2023Review
- Exaptation and Evolutionary Adaptation in Nociceptor Mechanisms Driving Persistent Pain.Brain, behavior and evolution · 2023Review
- Electrophysiological Alterations Driving Pain-Associated Spontaneous Activity in Human Sensory Neuron Somata Parallel Alterations Described in Spontaneously Active Rodent Nociceptors.The journal of pain · 2022Article
- Bioinformatics Analysis of the MicroRNA-Metabolic Gene Regulatory Network in Neuropathic Pain and Prediction of Corresponding Potential Therapeutics.Journal of molecular neuroscience : MN · 2022Article
- 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
- Reprogrammed mRNA translation drives resistance to therapeutic targeting of ribosome biogenesis.The EMBO journal · 2020Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
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
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