Review Article| Volume 234, P20-30, August 2021

Targeting T-type/CaV3.2 channels for chronic pain

  • Author Footnotes
    # Co-first authors.
    Song Cai
    Reprint requests: Song Cai, Department of Anatomy, Histology & Developmental Biology, School of Basic Medical Sciences, Shenzhen University Health Science Centre, Nanhai Ave 3688, Shenzhen, Guangdong Province, PR China 518060.
    # Co-first authors.
    Department of Anatomy, Histology & Developmental Biology, School of Basic Medical Sciences, Shenzhen University Health Science Centre, Shenzhen, Guangdong Province, PR China
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  • Author Footnotes
    # Co-first authors.
    Kimberly Gomez
    # Co-first authors.
    Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona
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  • Aubin Moutal
    Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona
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  • Rajesh Khanna
    Reprint requests: Rajesh Khanna, Department of Pharmacology, College of Medicine, University of Arizona, 1501 North Campbell Drive, P.O. Box 245050, Tucson, AZ 85724.
    Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona

    Comprehensive Pain and Addiction Center, The University of Arizona, Tucson, Arizona

    Regulonix LLC, Tucson, Arizona
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  • Author Footnotes
    # Co-first authors.
Published:January 07, 2021DOI:
      T-type calcium channels regulate neuronal excitability and are important contributors of pain processing. CaV3.2 channels are the major isoform expressed in nonpeptidergic and peptidergic nociceptive neurons and are emerging as promising targets for pain treatment. Numerous studies have shown that CaV3.2 expression and/or activity are significantly increased in spinal dorsal horn and in dorsal root ganglia neurons in different inflammatory and neuropathic pain models. Pharmacological campaigns to inhibit the functional expression of CaV3.2 for treatment of pain have focused on the development of direct channel blockers, but none have produced lead candidates. Targeting the proteins that regulate the trafficking or transcription, and the ones that modify the channels via post-translational modifications are alternative means to regulate expression and function of CaV3.2 channels and hence to develop new drugs to control pain. Here we synthesize data supporting a role for CaV3.2 in numerous pain modalities and then discuss emerging opportunities for the indirect targeting of CaV3.2 channels.



      AP (action potentials), CaV3.2 (voltage-gated calcium channel subfamily CaV3.2), CCD (chronic compression of DRG), CCI (chronic constriction injury), Cdk5 (cyclin-dependent kinase 5), CFA (complete Freund's adjuvant), CIPN (chemotherapy induced peripheral neuropathy), CRMP2 (collapsin response mediator protein), DRG (dorsal root ganglion), Egr-1 (early growth response 1), IGF-1 (insulin-like growth factor 1), HMGB1 (high mobility group box 1), HVA (high voltage-activated), H2S (hydrogen sulfide), LTMR (low-threshold mechanoreceptor), LVA (low-voltage activated), N2O (nitrous oxide), PDN (Peripheral diabetic neuropathy), PMA (phorbol 12-myristate 13-acetate), PKCα (protein kinase Cα), pSNL (partial sciatic nerve ligation), RAGE (receptor for advanced glycation end-products), REST (repressor element 1-silencing transcription factor), SDH (spinal dorsal horn), SNI (spared nerve injury), SNL (spinal nerve ligation), STZ (Streptozotocin), SUMO (small ubiquitin-related modifier), TTX-R (tetrodotoxin-resistant Na+ currents), USP5 (ubiquitin-specific cysteine protease 5/ isopeptidase T), WW1 (WW Domain Containing E3 Ubiquitin Protein Ligase 1)
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