Spinal Involvement of TRPV1 and PI3K/AKT/mTOR Pathway During Chronic Postoperative Pain in Mice.

IF 2.8 3区 医学 Q3 NEUROSCIENCES Brain Sciences Pub Date : 2025-01-08 DOI:10.3390/brainsci15010053
Gabriela Xavier Santos, Tayllon Dos Anjos-Garcia, Ana Carolina de Jesus Vieira, Giovane Galdino
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Abstract

Background: Chronic postoperative pain (CPOP) is among the main consequences of surgical procedures, directly affecting the quality of life. Although many strategies have been used to treat this symptom, they are often ineffective. Thus, studies investigating CPOP-associated mechanisms may help to develop more effective treatment strategies. Therefore, the present study investigated the spinal participation of the transient potential receptor vanilloid type 1 (TRPV1) and PI3K/AKT/mTOR pathway activation during CPOP.

Methods: In this study C57BL/6 male mice were used, and CPOP was induced by muscle retraction and incision. The nociceptive threshold was measured by the von Frey filament test. For pharmacological evaluation, TRPV1 and PI3K/AKT/mTOR inhibitors were administered intrathecally. TRPV1 and PI3K/AKT/mTOR protein levels were evaluated by Western blotting.

Results: The results showed that CPOP increased TRPV1 and mTOR protein levels, and pretreatment with the specific inhibitors alleviated CPOP. In addition, pretreatment with the TRPV1 antagonist SB-366791 attenuated mTOR protein levels.

Conclusions: The results suggest that TRPV1 and the PI3K/AKT/mTOR pathway are involved in CPOP at the spinal level, and TRPV1 may activate mTOR during this process.

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小鼠术后慢性疼痛中TRPV1和PI3K/AKT/mTOR通路的脊柱受累
背景:慢性术后疼痛(CPOP)是外科手术的主要后果之一,直接影响生活质量。虽然有许多策略被用来治疗这种症状,但它们往往无效。因此,研究cpop相关机制可能有助于制定更有效的治疗策略。因此,本研究探讨了CPOP期间脊髓参与瞬时电位受体香草样蛋白1型(TRPV1)和PI3K/AKT/mTOR通路激活的情况。方法:以C57BL/6雄性小鼠为实验对象,采用肌肉收缩和切口诱导CPOP。伤害性阈值采用von Frey细丝法测定。为了进行药理学评估,在鞘内给予TRPV1和PI3K/AKT/mTOR抑制剂。Western blotting检测TRPV1和PI3K/AKT/mTOR蛋白水平。结果:CPOP使TRPV1和mTOR蛋白水平升高,特异性抑制剂预处理可减轻CPOP的作用。此外,TRPV1拮抗剂SB-366791预处理可降低mTOR蛋白水平。结论:TRPV1和PI3K/AKT/mTOR通路在脊髓水平参与CPOP, TRPV1可能在此过程中激活mTOR。
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来源期刊
Brain Sciences
Brain Sciences Neuroscience-General Neuroscience
CiteScore
4.80
自引率
9.10%
发文量
1472
审稿时长
18.71 days
期刊介绍: Brain Sciences (ISSN 2076-3425) is a peer-reviewed scientific journal that publishes original articles, critical reviews, research notes and short communications in the areas of cognitive neuroscience, developmental neuroscience, molecular and cellular neuroscience, neural engineering, neuroimaging, neurolinguistics, neuropathy, systems neuroscience, and theoretical and computational neuroscience. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.
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