ArticlePloS one2015
Carbonic anhydrase-8 regulates inflammatory pain by inhibiting the ITPR1-cytosolic free calcium pathway.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Applications of Carbonic Anhydrase Inhibitors in Neurological Disorders, Mechanisms and Therapeutic Potential.Sub-cellular biochemistry · 2026Review
- ER stress-induced ITPR1/ANO1 signaling drives trigeminal neuropathic pain through calcium-dependent neuronal hyperexcitability.The journal of headache and pain · 2025Article
- Biosafety and efficacy of Kv7 activating rdHSV-CA8∗ analgesic gene therapy for chronic pain via the intra-articular route in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The Integrated Transcriptome Bioinformatics Analysis of Energy Metabolism-Related Profiles for Dorsal Root Ganglion of Neuropathic Pain.Molecular neurobiology · 2025Article
- Chronic vertigo and central oculomotor dysfunction with evidence of anti-ITPR1 antibodies.Journal of neurology · 2025Article
- Carbonic anhydrase 8 regulates basophil activation and interleukin 4 production.Frontiers in immunology · 2025Article
- Carbonic anhydrase inhibitor alleviates retinal barrier toxicity in paclitaxel-induced retinopathy and macular edema by inhibiting CAXIV.International ophthalmology · 2024Article
- Cytokines reprogram airway sensory neurons in asthma.bioRxiv : the preprint server for biology · 2024Article
- Disease-modifying rdHSV-CA8* non-opioid analgesic gene therapy treats chronic osteoarthritis pain by activating Kv7 voltage-gated potassium channels.Frontiers in molecular neuroscience · 2024Article
- rdHSV-CA8 non-opioid analgesic gene therapy decreases somatosensory neuronal excitability by activating Kv7 voltage-gated potassium channels.Frontiers in molecular neuroscience · 2024Article
- scRNA-seq generates a molecular map of emerging cell subtypes after sciatic nerve injury in rats.Communications biology · 2022Article
- Sensory neuron inositol 1,4,5-trisphosphate receptors contribute to chronic mechanoreflex sensitization in rats with simulated peripheral artery disease.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Thromboxane APhysiological reports · 2021Article
- Exaggerated sympathetic and cardiovascular responses to dynamic mechanoreflex activation in rats with heart failure: Role of endoperoxide 4 and thromboxane AAutonomic neuroscience : basic & clinical · 2021Article
- Alterations in the CaExploration of targeted anti-tumor therapy · 2021Article
- Reversion mutation of cDNA CA8-204 minigene construct produces a truncated functional peptide that regulates calcium release in vitro and produces profound analgesia in vivo.Mammalian genome : official journal of the International Mammalian Genome Society · 2020Article
- Thromboxane AAmerican journal of physiology. Heart and circulatory physiology · 2020Article
- Gene expression profiles for low-dose exposure to diethyl phthalate in rodents and humans: a translational study with implications for breast carcinogenesis.Scientific reports · 2020Article
- Structural Characterization of Carbonic Anhydrase VIII and Effects of Missense Single Nucleotide Variations to Protein Structure and Function.International journal of molecular sciences · 2020Article
- Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA-mRNA Interaction Involvement.International journal of molecular sciences · 2020Article
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
Calcium dysregulation is causally linked with various forms of neuropathology including seizure disorders, multiple sclerosis, Huntington's disease, Alzheimer's, spinal cerebellar ataxia (SCA) and chronic pain. Carbonic anhydrase-8 (Car8) is an allosteric inhibitor of inositol trisphosphate receptor-1 (ITPR1), which regulates intracellular calcium release fundamental to critical cellular functions including neuronal excitability, neurite outgrowth, neurotransmitter release, mitochondrial energy production and cell fate. In this report we test the hypothesis that Car8 regulation of ITPR1 and cytoplasmic free calcium release is critical to nociception and pain behaviors. We show Car8 null mutant mice (MT) exhibit mechanical allodynia and thermal hyperalgesia. Dorsal root ganglia (DRG) from MT also demonstrate increased steady-state ITPR1 phosphorylation (pITPR1) and cytoplasmic free calcium release. Overexpression of Car8 wildtype protein in MT nociceptors complements Car8 deficiency, down regulates pITPR1 and abolishes thermal and mechanical hypersensitivity. We also show that Car8 nociceptor overexpression alleviates chronic inflammatory pain. Finally, inflammation results in downregulation of DRG Car8 that is associated with increased pITPR1 expression relative to ITPR1, suggesting a possible mechanism of acute hypersensitivity. Our findings indicate Car8 regulates the ITPR1-cytosolic free calcium pathway that is critical to nociception, inflammatory pain and possibly other neuropathological states. Car8 and ITPR1 represent new therapeutic targets for chronic pain.
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