Reassessment of capsaicin desensitization in the rodent spinal dorsal horn

IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemistry international Pub Date : 2024-10-20 DOI:10.1016/j.neuint.2024.105887
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Abstract

Capsaicin activates primary afferent transient receptor potential vanilloid 1 (TRPV1) in the spinal dorsal horn and induces exaggerated glutamate release. This capsaicin action is followed by a lasting refractory state referred to as “capsaicin desensitization”, which is considered a presynaptic event. In this study, using whole-cell recordings and holographic photostimulation, we reassessed this notion by investigating presynaptic glutamate release and the postsynaptic glutamate response during capsaicin administration. We found that both presynaptic synchronous glutamate release and the postsynaptic glutamate response were largely attenuated in this refractory state; in contrast, asynchronous release was exaggerated. Further behavioral studies revealed a quick increase in the mechanical pain threshold with intrathecal capsaicin administration. Taken together, both presynaptic synchronous glutamate release and the postsynaptic response are downregulated during capsaicin desensitization, and this desensitization may transiently increase the pain threshold. Since both presynaptic synchronous release and postsynaptic glutamate responses are attenuated, the traditional electrophysiological evidence supporting capsaicin desensitization as a presynaptic event should be reassessed.
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重新评估啮齿类动物脊髓背角的辣椒素脱敏。
辣椒素可激活脊髓背角的初级传入瞬时受体电位类香草素 1(TRPV1),并诱导谷氨酸的大量释放。这种辣椒素作用之后会出现一种持久的折射状态,被称为 "辣椒素脱敏",它被认为是一种突触前事件。在本研究中,我们使用全细胞记录和全息光刺激,通过研究辣椒素给药期间突触前谷氨酸释放和突触后谷氨酸反应,重新评估了这一概念。我们发现,在这种难治性状态下,突触前同步谷氨酸释放和突触后谷氨酸反应在很大程度上被削弱;相反,异步释放被夸大。进一步的行为学研究表明,鞘内注射辣椒素可迅速提高机械痛阈。综上所述,在辣椒素脱敏过程中,突触前同步谷氨酸释放和突触后反应都被下调,这种脱敏可能会短暂提高痛阈。由于突触前同步释放和突触后谷氨酸反应都会减弱,支持辣椒素脱敏是突触前事件的传统电生理学证据应该重新评估。
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来源期刊
Neurochemistry international
Neurochemistry international 医学-神经科学
CiteScore
8.40
自引率
2.40%
发文量
128
审稿时长
37 days
期刊介绍: Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.
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