抑制 P2X3 和 P2X2/3 受体可产生一致的镇痛效果：临床前研究的系统回顾和元分析》。

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology Pub Date : 2024-10-10 DOI:10.1016/j.ejphar.2024.177052

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引用次数: 0

摘要

背景：P2X3和P2X2/3受体是很有希望的疼痛治疗靶点，目前正在临床试验中评估选择性抑制剂。在此，我们旨在整合并定量评估有关 P2X3 和 P2X2/3 受体抑制剂治疗疼痛的临床前证据：方法：2023 年 8 月 5 日，我们在 PubMed、Scopus 和 Web-of-Science 上进行了文献检索。采用随机效应模型提取数据并进行荟萃分析，以估算干预措施的镇痛疗效；然后进行了几项亚组分析：结果：共纳入 67 篇文章。干预对疼痛的减轻效果一致（66.5 [CI95% = 58.5, 74.5]; p < 0.0001），其中内脏痛的减轻效果最高（114.3），其次是肌肉痛（79.8）和神经痛（71.1），但癌症痛（64.1）、关节痛（57.5）和炎症痛（49.0）的减轻效果较低。进一步分析表明，与热过敏（64.5）和疼痛相关行为（54.1）相比，机械过敏（70.4）的影响更大。性别（雄性或雌性）或种间（小鼠或大鼠）差异不明显（P > 0.05）。使用最多的分子是 A-317491，但其他分子如吉法酯或艾利匹酯也有效（所有分子的 p < 0.0001）。全身或外周给药的镇痛效果高于鞘内给药。相反，脑室内给药不仅没有镇痛作用，反而会加剧疼痛：结论：P2X3 和 P2X2/3 受体抑制剂在临床前研究中表现出良好的镇痛效果，这取决于疼痛的病因、疼痛的测量结果、所用药物及其给药途径。要评估这些临床前研究结果的临床实用性，还需要进一步的研究：PROCMPERO.ID：CRD42023450685。

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P2X3 and P2X2/3 receptors inhibition produces a consistent analgesic efficacy: A systematic review and meta-analysis of preclinical studies

Background

P2X3 and P2X2/3 receptors are promising therapeutic targets for pain treatment and selective inhibitors are under evaluation in ongoing clinical trials. Here we aim to consolidate and quantitatively evaluate the preclinical evidence on P2X3 and P2X2/3 receptors inhibitors for pain treatment.

Methods

A literature search was conducted in PubMed, Scopus and Web-of-Science on August 5, 2023. Data was extracted and meta-analyzed using a random-effects model to estimate the analgesic efficacy of the intervention; then several subgroup analyses were performed.

Results

67 articles were included. The intervention induced a consistent pain reduction (66.5 [CI95% = 58.5, 74.5]; p < 0.0001), which was highest for visceral pain (114.3), followed by muscle (79.8) and neuropathic pain (71.1), but lower for cancer (64.1), joint (57.5) and inflammatory pain (49.0). Further analysis showed a greater effect for mechanical hypersensitivity (70.4) compared to heat hypersensitivity (64.5) and pain-related behavior (54.1). Sex (male or female) or interspecies (mice or rats) differences were not appreciated (p > 0.05). The most used molecule was A-317491, but other such as gefapixant or eliapixant were also effective (p < 0.0001 for all). The analgesic effect was higher for systemic or peripheral administration than for intrathecal administration. Conversely, intracerebroventricular administration was not analgesic, but potentiated pain.

Conclusion

P2X3 and P2X2/3 receptor inhibitors showed a good analgesic efficacy in preclinical studies, which was dependent on the pain etiology, pain outcome measured, the drug used and its route of administration. Further research is needed to assess the clinical utility of these preclinical findings.

Protocol registration

PROSPERO ID CRD42023450685.

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来源期刊

European journal of pharmacology 医学-药学

CiteScore

9.00

自引率

0.00%

发文量

572

审稿时长

34 days

期刊介绍： The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems. The scope includes: Behavioural pharmacology Neuropharmacology and analgesia Cardiovascular pharmacology Pulmonary, gastrointestinal and urogenital pharmacology Endocrine pharmacology Immunopharmacology and inflammation Molecular and cellular pharmacology Regenerative pharmacology Biologicals and biotherapeutics Translational pharmacology Nutriceutical pharmacology.