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Surfen is a broad-spectrum calcium channel inhibitor with analgesic properties in mouse models of acute and chronic inflammatory pain

  • Ion Channels, Receptors and Transporters
  • Published:
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Abstract

Multiple voltage-gated calcium channels (VGCCs) contribute to the processing of nociceptive signals in primary afferent fibers. In addition, alteration of calcium channel activity is associated with a number of chronic pain conditions. Therefore, VGCCs have emerged as prime target for the management of either neuropathic or inflammatory pain, and selective calcium channel blockers have been shown to have efficacy in animal models and in the clinic. However, considering that multiple calcium channels contribute pain afferent signaling, broad-spectrum inhibitors of several channel isoforms may offer a net advantage in modulating pain. Here, we have analyzed the ability of the compound surfen to modulate calcium channels, and assessed its analgesic potential. We show that surfen is an equipotent blocker of both low- and high-voltage-activated calcium channels. Furthermore, spinal (intrathecal) delivery of surfen to mice produces sustained analgesia against both acute and chronic pain. Collectively, our data establish surfen as a broad-spectrum calcium channel inhibitor with analgesic potential, and raise the possibility of using surfen-derived compounds for the development of new pain-relieving drugs.

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Authors and Affiliations

  1. Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic

    Paula Rivas-Ramirez & Norbert Weiss

  2. Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Canada

    Vinicius M. Gadotti & Gerald W. Zamponi

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  1. Paula Rivas-Ramirez
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  2. Vinicius M. Gadotti
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  3. Gerald W. Zamponi
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Correspondence to Norbert Weiss.

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Work in the Weiss laboratory is supported by the Czech Science Foundation (grant 15-13556S), the Czech Ministry of Education Youth and Sports (grant 7AMB15FR015), and the Institute of Organic Chemistry and Biochemistry (IOCB). GWZ is a Canada Research Chair and supported by the Canadian Institutes of Health Research.

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Rivas-Ramirez, P., Gadotti, V.M., Zamponi, G.W. et al. Surfen is a broad-spectrum calcium channel inhibitor with analgesic properties in mouse models of acute and chronic inflammatory pain. Pflugers Arch - Eur J Physiol 469, 1325–1334 (2017). https://doi.org/10.1007/s00424-017-2017-8

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