Methylglyoxal activates transient receptor potential A1/V1 via reactive oxygen species in the spinal dorsal horn.

IF 2.8 3区 医学 Q2 NEUROSCIENCES
Takeru Ueno, Manabu Yamanaka, Wataru Taniguchi, Naoko Nishio, Yuki Matsuyama, Ryo Miyake, Yuta Kaimochi, Terumasa Nakatsuka, Hiroshi Yamada
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引用次数: 0

Abstract

Methylglyoxal (MGO), a highly reactive dicarbonyl metabolite of glucose primarily formed during the glycolytic pathway, is a precursor of advanced glycation end-products (AGEs). Recently, numerous studies have shown that MGO accumulation can cause pain and hyperalgesia. However, the mechanism through which MGO induces pain in the spinal dorsal horn remains unclear. The present study investigated the effect of MGO on spontaneous excitatory postsynaptic currents (sEPSC) in rat spinal dorsal horn neurons using blind whole-cell patch-clamp recording. Perfusion of MGO increased the frequency and amplitude of sEPSC in spinal horn neurons in a concentration-dependent manner. Additionally, MGO administration increased the number of miniature EPSC (mEPSC) in the presence of tetrodotoxin, a sodium channel blocker. However, 6-cyano-7-nitroqiunocaline-2,3-dione (CNQX), an AMPA/kainate receptor antagonist, blocked the enhancement of sEPSC by MGO. HC-030031, a TRP ankyrin-1 (TRPA1) antagonist, and capsazepine, a TRP vanilloid-1 (TRPV1) antagonist, inhibited the action of MGO. Notably, the effects of MGO were completely inhibited by HC-030031 and capsazepine. MGO generates reactive oxygen species (ROS) via AGEs. ROS also potentially induce pain via TRPA1 and TRPV1 in the spinal dorsal horn. Furthermore, we examined the effect of MGO in the presence of N-tert-butyl-α-phenylnitrone (PBN), a non-selective ROS scavenger, and found that the effect of MGO was completely inhibited. These results suggest that MGO increases spontaneous glutamate release from the presynaptic terminal to spinal dorsal horn neurons through TRPA1, TRPV1, and ROS and could enhance excitatory synaptic transmission.

甲基乙二酸通过脊髓背角的活性氧激活瞬时受体电位 A1/V1
甲基乙二醛(MGO)是葡萄糖的一种高活性二羰基代谢产物,主要在糖酵解途径中形成,是高级糖化终产物(AGEs)的前体。最近,大量研究表明,MGO 的积累可导致疼痛和痛觉减退。然而,MGO 在脊髓背角诱发疼痛的机制仍不清楚。本研究采用盲法全细胞贴片钳记录法研究了 MGO 对大鼠脊髓背角神经元自发兴奋突触后电流(sEPSC)的影响。灌注 MGO 能以浓度依赖性方式增加脊髓角神经元的 sEPSC 频率和振幅。此外,在钠通道阻滞剂河豚毒素存在的情况下,灌注 MGO 还能增加微型 EPSC(mEPSC)的数量。然而,AMPA/kainate 受体拮抗剂 6-氰基-7-硝基喹喔啉-2,3-二酮(CNQX)阻断了 MGO 对 sEPSC 的增强作用。TRP ankyrin-1 (TRPA1) 拮抗剂 HC-030031 和 TRP vanilloid-1 (TRPV1) 拮抗剂 capsazepine 抑制了 MGO 的作用。值得注意的是,HC-030031 和卡扎西平能完全抑制 MGO 的作用。MGO 通过 AGEs 产生活性氧(ROS)。ROS还可能通过脊髓背角的TRPA1和TRPV1诱发疼痛。此外,我们还研究了 MGO 在非选择性 ROS 清除剂 N-叔丁基-α-苯基硝酮(PBN)存在下的效应,发现 MGO 的效应被完全抑制。这些结果表明,MGO 可通过 TRPA1、TRPV1 和 ROS 增加突触前末端到脊髓背角神经元的自发谷氨酸释放,并可增强兴奋性突触传递。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Pain
Molecular Pain 医学-神经科学
CiteScore
5.60
自引率
3.00%
发文量
56
审稿时长
6-12 weeks
期刊介绍: Molecular Pain is a peer-reviewed, open access journal that considers manuscripts in pain research at the cellular, subcellular and molecular levels. Molecular Pain provides a forum for molecular pain scientists to communicate their research findings in a targeted manner to others in this important and growing field.
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