Potent analgesic effects of a store-operated calcium channel inhibitor

Ruby Gao, Xinghua Gao, Jingsheng Xia, Yuzhen Tian, James E. Barrett, Yue Dai, Huijuan Hu

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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 10 mg/kg or 30 mg/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 30 mg/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.

Original languageEnglish (US)
Pages (from-to)2034-2044
Number of pages11
JournalPain
Volume154
Issue number10
DOIs
StatePublished - Oct 2013

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All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Keywords

  • Dorsal root ganglia Inflammation Pain Store-operated calcium channels Tumor necrosis factor alpha YM-58483

Cite this

Gao, R., Gao, X., Xia, J., Tian, Y., Barrett, J. E., Dai, Y., & Hu, H. (2013). Potent analgesic effects of a store-operated calcium channel inhibitor. Pain, 154(10), 2034-2044. https://doi.org/10.1016/j.pain.2013.06.017