Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, Uttar Pradesh, India.
Neuroscience & Pain Research Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.
Neuromolecular Med. 2024 Nov 25;26(1):48. doi: 10.1007/s12017-024-08809-x.
Recent evidence highlights microparticles (MPs) as crucial players in intercellular communication among immune cells, yet their role in inflammation-induced chronic pain remains unexplored. In this study, we investigated the involvement of MPs in the progression of inflammation and associated pain using mouse models of chronic neuroinflammation induced by repeated intraperitoneal injections of lipopolysaccharide (LPS; 1 mg/kg for four consecutive days) in C57BL/6 mice. Chronic pain was analyzed at baseline (day 0) and on day 21 post-LPS injection using von Frey and the hot metal plate tests. We found a significant increase in the levels of proinflammatory mediators and activation of the TLR4-NFκB signaling pathways following LPS administration. Additionally, transcriptional upregulation of chronic pain-associated TRP channels and glutamate receptors, including TRPA1, TRPM2, and mGluR2 in the cortex and hippocampus as well as mGluR5 in the cortex, was noted on day 21 post-LPS injection. Moreover, upregulation of TRPM2, mGluR2, and mGluR5 was found in the spinal cord, along with increased TRPA1 protein expression in the brain cortex. Plasma-derived MPs were isolated, revealing a significant increase in concentration 21 days after LPS injection, accompanied by TNF-α DNA encapsulation and increased TNF-α mRNA expression within MPs. Furthermore, MPs concentration positively correlated with the expression of TRPA1, TRPM2, mGluR2, and mGluR5. These findings suggest that MPs contribute to inflammation-induced chronic pain, highlighting their potential as therapeutic targets.
最近的证据强调了微粒（MPs）作为免疫细胞之间细胞间通讯的关键参与者的作用，但它们在炎症引起的慢性疼痛中的作用仍未得到探索。在这项研究中，我们使用 C57BL/6 小鼠中由重复腹腔内注射脂多糖（LPS；1mg/kg，连续 4 天）引起的慢性神经炎症模型，研究 MPs 在炎症进展和相关疼痛中的作用。在基线（第 0 天）和 LPS 注射后第 21 天，使用 von Frey 和热金属板测试分析慢性疼痛。我们发现，LPS 给药后，促炎介质水平升高，TLR4-NFκB 信号通路激活。此外，在 LPS 注射后第 21 天，皮质和海马中的慢性疼痛相关 TRP 通道和谷氨酸受体（包括 TRPA1、TRPM2 和 mGluR2）以及皮质中的 mGluR5 的转录水平上调。此外，在脊髓中发现 TRPM2、mGluR2 和 mGluR5 的上调，以及大脑皮质中 TRPA1 蛋白表达增加。分离血浆衍生的 MPs，发现 LPS 注射 21 天后浓度显著增加，伴随 TNF-α DNA 包裹和 MPs 内 TNF-α mRNA 表达增加。此外， MPs 浓度与 TRPA1、TRPM2、mGluR2 和 mGluR5 的表达呈正相关。这些发现表明 MPs 有助于炎症引起的慢性疼痛，突出了它们作为治疗靶点的潜力。
