Potent analgesic effects of a store-operated calcium channel inhibitor.
Potent analgesic effects of a store-operated calcium channel inhibitor.
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作者：
Gao R;Gao X;Xia J;Tian Y;Barrett JE;Dai Y;Hu H
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's 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 administered systemically, intrathecally, and also 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 dose-dependently. YM-58483 produced antinociception in acute pain induced by heat or chemical or mechanical stimuli at the 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 non-nociceptors. 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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DOI：
10.1523/jneurosci.5053-10.2011
发表时间：
2011-03-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Gemes G;Bangaru ML;Wu HE;Tang Q;Weihrauch D;Koopmeiners AS;Cruikshank JM;Kwok WM;Hogan QH
通讯作者：
Hogan QH
影响因子：
4.8
作者：
He, LP;Hewavitharana, T;Gill, DL
通讯作者：
Gill, DL
影响因子：
4.8
作者：
Hu, HZ;Gu, QH;Zhu, MX
通讯作者：
Zhu, MX
影响因子：
7.4
作者：
Austin, Paul J.;Kim, Cristina F.;Moalem-Taylor, Gila
通讯作者：
Moalem-Taylor, Gila
影响因子：
4.4
作者：
Ishikawa, J;Ohga, K;Yamada, T
通讯作者：
Yamada, T