Veratramine Alleviates Neuropathic Pain in Male Rats With Chronic Constriction Injury and Inhibits the PI3K/Akt Pathway

IF 3.8 2区医学 Q1 ANESTHESIOLOGY

European Journal of Pain Pub Date : 2026-10-14 DOI:10.1002/ejp.70383

Yaoping Yu, Lijun Wang, Jie Cui, Yu Zhang, Fei Zhang

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Abstract

Background

Neuropathic pain (NP), a debilitating complication of chronic diseases such as diabetes and cancer, remains inadequately managed by current therapies; approximately 30% of patients are unresponsive to monotherapy. This study investigates the effects and potential mechanisms of veratramine, a natural compound, in a rodent model of chronic constriction injury (CCI)–induced neuropathic pain.

Methods

NP was induced via CCI in rodents. Veratramine's effects were assessed through behavioural tests (mechanical withdrawal threshold [MWT] and thermal withdrawal latency [TWL]). Apoptosis and inflammation in the sciatic nerve were analysed. Western blotting and immunofluorescence evaluated phosphorylation of NF-κB, IκB, p38 MAPK, and spinal glial activation. Transcriptome profiling identified key pathways, validated using the PI3K/Akt agonist 740 Y-P.

Results

Veratramine significantly increased MWT and TWL, alleviating mechanical and thermal hypersensitivity. It reduced neuronal apoptosis and inflammatory cytokine release at injury sites. Protein analysis showed suppressed phosphorylation of NF-κB, IκB, and p38 MAPK, alongside reduced numbers of Iba-1-positive and GFAP-positive cells in the spinal dorsal horn. Transcriptome data implicated PI3K/Akt signalling pathway inhibition, confirmed by 740 Y-P co-treatment reversing veratramine's anti-inflammatory and analgesic effects.

Conclusion

These findings indicate that veratramine attenuates neuropathic pain in CCI rats, and its effects may involve inhibition of the PI3K/Akt signalling pathway, leading to reduced neuroinflammation and apoptosis. This study supports a role for veratramine in the modulation of neuropathic pain and highlights the PI3K/Akt pathway as a potential target for further investigation.

Significance Statement

The results of this study suggest that veratramine alleviates neuropathic pain in a rat model of CCI, and this effect is associated with suppression of the PI3K/Akt signalling pathway. These findings support a role for veratramine in modulating neuroinflammation and apoptosis, and may contribute to a better understanding of the molecular mechanisms involved in neuropathic pain.

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Veratramine减轻慢性收缩性损伤雄性大鼠神经性疼痛及抑制PI3K/Akt通路

背景：神经性疼痛（NP）是慢性疾病（如糖尿病和癌症）的一种使人衰弱的并发症，目前的治疗方法仍然不能充分控制；大约30%的患者对单药治疗无反应。本研究探讨了天然化合物veratramine在慢性收缩损伤（CCI）诱导的神经性疼痛啮齿动物模型中的作用及其潜在机制。方法：采用CCI诱导小鼠NP。通过行为测试（机械戒断阈值[MWT]和热戒断潜伏期[TWL]）评估Veratramine的效果。分析了坐骨神经的细胞凋亡和炎症反应。Western blotting和免疫荧光检测NF-κB、i -κB、p38 MAPK磷酸化和脊髓胶质细胞活化。转录组分析鉴定了关键通路，使用PI3K/Akt激动剂740 Y-P进行了验证。结果：Veratramine显著提高MWT和TWL，减轻机械和热超敏反应。减少损伤部位的神经元凋亡和炎性细胞因子释放。蛋白分析显示NF-κB、i -κB和p38 MAPK的磷酸化受到抑制，同时脊髓背角中iba -1阳性和gfap阳性细胞数量减少。转录组数据表明PI3K/Akt信号通路受到抑制，740 Y-P联合治疗逆转了veratramine的抗炎和镇痛作用。结论：veratramine可减轻CCI大鼠的神经性疼痛，其作用可能与抑制PI3K/Akt信号通路有关，从而减少神经炎症和细胞凋亡。本研究支持veratramine在神经性疼痛调节中的作用，并强调PI3K/Akt通路是进一步研究的潜在靶点。意义声明：本研究结果提示，veratramine可减轻CCI大鼠模型的神经性疼痛，其作用与抑制PI3K/Akt信号通路有关。这些发现支持veratramine在调节神经炎症和细胞凋亡中的作用，并可能有助于更好地理解神经性疼痛的分子机制。

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

European Journal of Pain 医学-临床神经学

CiteScore

7.50

自引率

5.60%

发文量

163

审稿时长

4-8 weeks

期刊介绍： European Journal of Pain (EJP) publishes clinical and basic science research papers relevant to all aspects of pain and its management, including specialties such as anaesthesia, dentistry, neurology and neurosurgery, orthopaedics, palliative care, pharmacology, physiology, psychiatry, psychology and rehabilitation; socio-economic aspects of pain are also covered. Regular sections in the journal are as follows: • Editorials and Commentaries • Position Papers and Guidelines • Reviews • Original Articles • Letters • Bookshelf The journal particularly welcomes clinical trials, which are published on an occasional basis. Research articles are published under the following subject headings: • Neurobiology • Neurology • Experimental Pharmacology • Clinical Pharmacology • Psychology • Behavioural Therapy • Epidemiology • Cancer Pain • Acute Pain • Clinical Trials.