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Potent analgesic effects of a store-operated calcium channel inhibitor
Journal article   Open access   Peer reviewed

Potent analgesic effects of a store-operated calcium channel inhibitor

Ruby Gao, Xinghua Gao, Jingsheng Xia, Yuzhen Tian, James E. Barrett, Yue Dai and Huijuan Hu
Pain (Amsterdam), v 154(10), pp 2034-2044
Oct 2013
DOI: https://doi.org/10.1016/j.pain.2013.06.017
PMID: 23778292
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc3778044View
Accepted (AM) Open Open Access (License Unspecified)

Abstract

Dorsal root ganglia Inflammation Pain Store-operated calcium channels Tumor necrosis factor alpha YM-58483
The SOC channel inhibitor YM-58483 has analgesic actions in chronic pain, produces antinociceptive effects in acute pain and prevents the development of chronic pain in mice. Chronic pain often accompanies immune responses and immune cells are known to be involved in chronic pain. Store-operated calcium (SOC) channels are calcium-selective cation channels and play an important role in the immune system. YM-58483, a potent SOC channel inhibitor, has been shown to inhibit cytokine production from immune cells and attenuate antigen-induced hypersensitivity reactions. Here, we report that YM-58483 has analgesic actions in chronic pain and produces antinociceptive effects in acute pain and prevents the development of chronic pain in mice. Oral administration of 10mg/kg or 30mg/kg YM-58483 dramatically attenuated complete Freund adjuvant (CFA)-induced thermal hyperalgesia and prevented the development of thermal and mechanical hypersensitivity in a dose-dependent manner. Analgesic effects were observed when YM-58483 was administered systemically, intrathecally and intraplantarly. YM-58483 decreased spared nerve injury (SNI)-induced thermal and mechanical hypersensitivity and prevented the development of SNI-induced pain hypersensitivity. Pretreatment with YM-58483 strongly reduced both the first and second phases of formalin-induced spontaneous nocifensive behavior in a dose-dependent manner. YM-58483 produced antinociception in acute pain induced by heat or chemical or mechanical stimuli at a dose of 30mg/kg. YM-58483 diminished CFA-induced paw edema, and reduced production of TNF-α, IL-1β and PGE2 in the CFA-injected paw. In vitro, SOC entry in nociceptors was more robust than in nonnociceptors, and the inhibition of SOC entry by YM-58483 in nociceptors was much greater than in nonnociceptors. Our findings indicate that YM-58483 is a potent analgesic and suggest that SOC channel inhibitors may represent a novel class of therapeutics for pain.

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Collaboration types
Domestic collaboration
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Web of Science research areas
Anesthesiology
Clinical Neurology
Neurosciences
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