López-Tofiño Yolanda, López-Gómez Laura, Martín-Ruíz Marta, Uranga Jose Antonio, Nurgali Kulmira, Vera Gema, Abalo Raquel
Department of Basic Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain.
High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut), University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain.
Cells. 2024 Dec 30;14(1):26. doi: 10.3390/cells14010026.
Cisplatin, a chemotherapeutic drug, is known for causing gastrointestinal disorders and neuropathic pain, but its impact on visceral sensitivity is unclear. Monosodium glutamate (MSG) has been shown to improve gastrointestinal dysmotility and neuropathic pain induced by cisplatin in rats. This study aimed to determine if repeated cisplatin treatment alters visceral sensitivity and whether dietary MSG can prevent these changes. Male Wistar HAN rats were treated with saline or cisplatin (2 mg/kg/week, ip) for 5 weeks, and visceral sensitivity to intracolonic mechanical stimulation was recorded after the final cisplatin administration (week 5) and one-week post-treatment (week 6). In a second cohort, rats treated with cisplatin or saline also received MSG (4 g/L) in their drinking water, and visceral sensitivity was evaluated on week 6. Finally, the untouched distal colon was obtained from a third cohort of animals one week after treatment to assess immunocyte infiltration. Cisplatin significantly increased colonic mechanical sensitivity on week 6 but not on week 5. MSG did not prevent cisplatin-induced visceral hypersensitivity on week 6 and even exacerbated it. On week 6, compared with the control, cisplatin (with or without MSG) did not modify the colonic infiltration of eosinophils, macrophages, neutrophils, or mast cells. Although MSG seems to be useful in ameliorating some of the adverse effects of cisplatin, such as gastrointestinal motility disturbances or neuropathic pain, it does not alleviate visceral pain.
顺铂是一种化疗药物，以引起胃肠道疾病和神经性疼痛而闻名，但其对内脏敏感性的影响尚不清楚。已表明味精（MSG）可改善顺铂诱导的大鼠胃肠道运动障碍和神经性疼痛。本研究旨在确定重复给予顺铂治疗是否会改变内脏敏感性，以及饮食中的味精是否可以预防这些变化。雄性Wistar HAN大鼠用生理盐水或顺铂（2mg/kg/周，腹腔注射）治疗5周，并在最后一次给予顺铂后（第5周）和治疗后一周（第6周）记录对结肠内机械刺激的内脏敏感性。在第二个队列中，用顺铂或生理盐水治疗的大鼠在饮用水中也添加了味精（4g/L），并在第6周评估内脏敏感性。最后，在治疗一周后从第三组动物中获取未处理的远端结肠，以评估免疫细胞浸润情况。顺铂在第6周时显著增加了结肠机械敏感性，但在第5周时没有。味精在第6周时没有预防顺铂诱导的内脏超敏反应，甚至使其加剧。在第6周时，与对照组相比，顺铂（无论是否添加味精）均未改变嗜酸性粒细胞、巨噬细胞、中性粒细胞或肥大细胞在结肠中的浸润情况。尽管味精似乎有助于改善顺铂的一些不良反应，如胃肠道运动紊乱或神经性疼痛，但它并不能减轻内脏疼痛。
