Transient Receptor Potential Melastatin 8 Contributes to Cystitis-Induced Neuronal Sprouting and Pain Hypersensitivity Through AKT/mTOR Signaling Pathway in Interstitial Cystitis/Bladder Pain Syndrome

IF 1.5 4区医学 Q3 UROLOGY & NEPHROLOGY

LUTS: Lower Urinary Tract Symptoms Pub Date : 2024-11-11 DOI:10.1111/luts.12537

Liyang Wu, Ran Chang, Peng Zhang

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引用次数: 0

Abstract

Objectives

The aim of this study was to investigate the mechanism of TRPM8 in neuroproliferation and pain, as well as the relevance of the Akt/mTOR signaling pathway in mice with IC/BPS.

Methods

The model of IC/BPS was established in wild and TRPM8^−/− mice. The mechanical sensitivity was measured. The number of neurite segments, length of neurites, and density of neurites were all counted. IL-6 and norepinephrine levels were detected by ELISA, Western blot was used to detect protein levels of TRPM8, Akt, p-Akt, mTOR, p-mTOR. Immunofluorescence was used to detect TRPM8 expression and distribution in neurites, neurons, and sensory nerves in mouse bladder tissue.

Results

Pain threshold in the IC/BPS group was decreased, and neurite segments, length, and density were all significantly enhanced when compared to the control group. The parameters in the IC/BPS model + Menthol group were more statistically significant. Neurite number and density were lower in TRPM8 knockout-model mice than in IC/BPS model mice. The expression of TRPM8 and the ratios of p-Akt/Akt and p-mTOR/mTOR rose in the IC/BPS model group. In TRPM8 knockout-model mice, the ratios of p-Akt/Akt and p-mTOR/mTOR were not substantially different from those in the control group. TRPM8 knockout-model mice had considerably lower levels of serum IL-6 and urine norepinephrine than IC/BPS model mice.

Conclusions

TRPM8 can induce pain hypersensitivity and sensory nerve proliferation by activating Akt/mTOR pathway and raising the expression of IL-6 and norepinephrine in IC/BPS models. These findings offer new perspectives on IC/BPS treatment.

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瞬时受体电位美司他丁 8 通过 AKT/mTOR 信号通路促进间质性膀胱炎/膀胱疼痛综合征中膀胱炎诱导的神经元萌发和疼痛超敏反应

研究目的本研究旨在探讨 TRPM8 在 IC/BPS 小鼠神经增殖和疼痛中的作用机制，以及 Akt/mTOR 信号通路的相关性：方法：在野生小鼠和TRPM8-/-小鼠中建立IC/BPS模型。方法：在野生小鼠和TRPM8-/-小鼠中建立IC/BPS模型，测量机械敏感性。方法：在野生小鼠和 TRPM8-/- 小鼠中建立 IC/BPS 模型，测量机械敏感性，计算神经元节段数量、神经元长度和神经元密度。ELISA检测IL-6和去甲肾上腺素的水平，Western印迹检测TRPM8、Akt、p-Akt、mTOR、p-mTOR的蛋白水平。免疫荧光法检测TRPM8在小鼠膀胱组织神经元、神经元和感觉神经中的表达和分布：结果：与对照组相比，IC/BPS 组疼痛阈值降低，神经元节段、长度和密度均明显增加。IC/BPS 模型 + 薄荷醇组的参数在统计学上更为显著。TRPM8基因敲除模型小鼠的神经元数目和密度均低于IC/BPS模型小鼠。IC/BPS模型组中TRPM8的表达以及p-Akt/Akt和p-mTOR/mTOR的比率上升。在TRPM8基因敲除模型小鼠中，p-Akt/Akt和p-mTOR/mTOR的比率与对照组没有实质性差异。TRPM8基因敲除模型小鼠的血清IL-6和尿去甲肾上腺素水平大大低于IC/BPS模型小鼠：结论：在 IC/BPS 模型中，TRPM8 可通过激活 Akt/mTOR 通路并提高 IL-6 和去甲肾上腺素的表达，诱导痛觉过敏和感觉神经增生。这些发现为IC/BPS的治疗提供了新的视角。

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

LUTS: Lower Urinary Tract Symptoms UROLOGY & NEPHROLOGY-

CiteScore

3.00

自引率

7.70%

发文量

审稿时长

>12 weeks

期刊介绍： LUTS is designed for the timely communication of peer-reviewed studies which provides new clinical and basic science information to physicians and researchers in the field of neurourology, urodynamics and urogynecology. Contributions are reviewed and selected by a group of distinguished referees from around the world, some of whom constitute the journal''s Editorial Board. The journal covers both basic and clinical research on lower urinary tract dysfunctions (LUTD), such as overactive bladder (OAB), detrusor underactivity, benign prostatic hyperplasia (BPH), bladder outlet obstruction (BOO), urinary incontinence, pelvic organ prolapse (POP), painful bladder syndrome (PBS), as well as on other relevant conditions. Case reports are published only if new findings are provided. LUTS is an official journal of the Japanese Continence Society, the Korean Continence Society, and the Taiwanese Continence Society. Submission of papers from all countries are welcome. LUTS has been accepted into Science Citation Index Expanded (SCIE) with a 2011 Impact Factor.