Icilin reduces voltage-gated calcium channel currents in na茂ve and injured DRG neurons in the rat spinal nerve ligation model
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- 作者：T. Hagenacker ; tim.hagenacker@uk-essen.de" class="auth_mail ; M. Lampe ; M. Schä ; fers
- 关键词：TRPM8 ; transient receptor potential melastatin 8 ; TRPA1 ; transient receptor potential ankyrin 1 ; SNL ; spinal nerve ligation ; CCI ; chronic constriction injury ; DRG ; dorsal root ganglion ; VGCC ; voltage gated calcium channel ; EPSC ; excitatory postsynaptic current ; ICa(V) ; VGCC currents ; IV-curve ; current&ndash ; voltage relation
- 刊名：Brain Research
- 出版年：4 April, 2014
- 年：2014
- 卷：1557
- 期：Complete
- 页码：171-179
- 全文大小：1242 K
文摘
Recently, the transient receptor potential (TRP) channels TRPM8 and TRPA1 have been identified as molecular sensors for cold, and it has been suggested that they play a crucial role in allodynia by modulating voltage-gated calcium channel currents (ICa(V)). The aim of this study was to analyze the modulation of ICa(V) by the TRPM8-agonist icilin in vitro and to investigate the analgesic effect of icilin in a neuropathic pain model in vivo. Whole cell patch-clamp recordings were performed on isolated na茂ve and injured rat dorsal root ganglia (DRG) neurons, and the analgesic efficacy of icilin applied topically to the paws or intrathecally was tested in rats after spinal nerve ligation (SNL). ICa(V) (depolarization from 鈭?0 to 0 mV) in na茂ve DRG neurons was reduced dose dependently (0.002-200 碌M) by icilin (18-80%). Subtype isolation of calcium channels show a marked reduction of L-type channel currents compared to N-type channel currents. The effects of icilin on ICa(V) were not significantly different in non-injured and SNL-injured DRG neurons. In vivo, neither topical (10-200 碌M) nor intrathecal application of icilin (0.1 nM to 1 碌M) affected tactile allodynia or thermal hyperalgesia after SNL, but it increases cold allodynia 6 h after application. We conclude that the icilin-induced modulation of ICa(V) in DRG neurons is unlikely to mediate analgesic effects or contribute directly to the pathogenesis of cold allodynia in the rat SNL model, but it is a potential mechanism for the analgesic effects of icilin in other pain models.