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多次给予多酚提取物可通过调节脊髓损伤雌性小鼠的胶质增生和CCL2-CCR2/CX3CL1-CX3CR1信号通路,预防慢性反射性和非反射性神经性疼痛反应。

Repeated Administrations of Polyphenolic Extracts Prevent Chronic Reflexive and Non-Reflexive Neuropathic Pain Responses by Modulating Gliosis and CCL2-CCR2/CX3CL1-CX3CR1 Signaling in Spinal Cord-Injured Female Mice.

作者信息

Bagó-Mas Anna, Korimová Andrea, Bretová Karolína, Deulofeu Meritxell, Verdú Enrique, Fiol Núria, Dubový Petr, Boadas-Vaello Pere

机构信息

Research Group of Clinical Anatomy, Embryology and Neuroscience (NEOMA), Department of Medical Sciences, University of Girona, 17071 Girona, Catalonia, Spain.

Division of Neuroanatomy, Department of Anatomy, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic.

出版信息

Int J Mol Sci. 2025 Apr 2;26(7):3325. doi: 10.3390/ijms26073325.

Abstract

Neuropathic pain after spinal cord injury lacks any effective treatments, often leading to chronic pain. This study tested whether the daily administration of fully characterized polyphenolic extracts from grape stalks and coffee could prevent both reflexive and non-reflexive chronic neuropathic pain in spinal cord-injured mice by modulating the neuroimmune axis. Female CD1 mice underwent mild spinal cord contusion and received intraperitoneal extracts in weeks one, three, and six post-surgery. Reflexive pain responses were assessed weekly for up to 10 weeks, and non-reflexive pain was evaluated at the study's end. Neuroimmune crosstalk was investigated, focusing on glial activation and the expression of CCL2/CCR2 and CX3CL1/CX3CR1 in supraspinal pain-related areas, including the periaqueductal gray, rostral ventromedial medulla, anterior cingulate cortex, and amygdala. Repeated treatments prevented mechanical allodynia and thermal hyperalgesia, and also modulated non-reflexive pain. Moreover, they reduced supraspinal gliosis and regulated CCL2/CCR2 and CX3CL1/CX3CR1 signaling. Overall, the combination of polyphenols in these extracts may offer a promising pharmacological strategy to prevent chronic reflexive and non-reflexive pain responses by modifying central sensitization markers, not only at the contusion site but also in key supraspinal regions implicated in neuropathic pain. Overall, these data highlight the potential of polyphenolic extracts for spinal cord injury-induced chronic neuropathic pain.

摘要

脊髓损伤后的神经性疼痛缺乏有效的治疗方法,常常导致慢性疼痛。本研究测试了每日给予从葡萄茎和咖啡中提取的特征明确的多酚提取物,是否能够通过调节神经免疫轴,预防脊髓损伤小鼠的反射性和非反射性慢性神经性疼痛。雌性CD1小鼠接受轻度脊髓挫伤,并在术后第1、3和6周接受腹腔注射提取物。每周评估反射性疼痛反应,最长持续10周,并在研究结束时评估非反射性疼痛。研究神经免疫相互作用,重点关注与脊髓上疼痛相关区域(包括导水管周围灰质、延髓头端腹内侧、前扣带回皮层和杏仁核)中的胶质细胞活化以及CCL2/CCR2和CX3CL1/CX3CR1的表达。重复治疗可预防机械性异常性疼痛和热痛觉过敏,还可调节非反射性疼痛。此外,它们可减轻脊髓上胶质增生并调节CCL2/CCR2和CX3CL1/CX3CR1信号传导。总体而言,这些提取物中的多酚组合可能提供一种有前景的药理学策略,通过改变中枢敏化标志物来预防慢性反射性和非反射性疼痛反应,不仅在挫伤部位,而且在与神经性疼痛相关的关键脊髓上区域。总体而言,这些数据突出了多酚提取物对脊髓损伤诱导的慢性神经性疼痛的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe8/11989601/7230bea98e2b/ijms-26-03325-g001.jpg

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