Du Junying, Yi Min, Xi Danning, Wang Sisi, Liu Boyi, Shao Xiaomei, Liang Yi, He Xiaofen, Fang Jianqiao, Fang Junfan
Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, China.
Front Mol Neurosci. 2023 Feb 2;16:1089162. doi: 10.3389/fnmol.2023.1089162. eCollection 2023.
Chronic pain is one of the most common clinical syndromes affecting patients' quality of life. Regulating the transition from acute to chronic pain is a novel therapeutic strategy for chronic pain that presents a major clinical challenge. However, the mechanism underlying pain transitions remains poorly understood. A rat hyperalgesic priming (HP) model, which mimics pain transition, was established decades ago. Here, this HP model and RNA sequencing (RNA-seq) were used to study the potential role of neuroinflammation in pain transition. In this study, HP model rats developed prolonged hyperalgesia in the hind paw after carrageenan (Car) and PGE2 injection, accompanied by obvious satellite glial cell (SGC) activation in the dorsal root ganglion (DRG), as indicated by upregulation of GFAP. RNA-Seq identified a total of differentially expressed genes in the ipsilateral DRG in HP model rats. The expression of several representative genes was confirmed by real-time quantitative PCR (qPCR). Functional analysis of the differentially expressed genes indicated that genes related to the inflammatory and neuroinflammatory response showed the most significant changes in expression. We further found that the expression of the chemokine CXCL1 was significantly upregulated in the rat DRG. Pharmacological blockade of CXCL1 reduced protein kinase C epsilon overproduction as well as hyperalgesia in HP rats but did not prevent the upregulation of GFAP in the DRG. These results reveal that neuroinflammatory responses are involved in pain transition and may be the source of chronic pain. The chemokine CXCL1 in the DRG is a pivotal contributor to chronic pain and pain transition in HP model rats. Thus, our study provides a putative novel target for the development of effective therapeutics to prevent pain transition.
慢性疼痛是影响患者生活质量的最常见临床综合征之一。调节从急性疼痛到慢性疼痛的转变是一种针对慢性疼痛的新型治疗策略，但这带来了重大的临床挑战。然而，疼痛转变背后的机制仍知之甚少。数十年前建立了一种模拟疼痛转变的大鼠痛觉过敏预处理（HP）模型。在此，利用该HP模型和RNA测序（RNA-seq）来研究神经炎症在疼痛转变中的潜在作用。在本研究中，HP模型大鼠在注射角叉菜胶（Car）和前列腺素E2（PGE2）后后爪出现了延长的痛觉过敏，同时背根神经节（DRG）中卫星胶质细胞（SGC）明显激活，胶质纤维酸性蛋白（GFAP）上调表明了这一点。RNA-Seq鉴定出HP模型大鼠同侧DRG中共有差异表达基因。通过实时定量PCR（qPCR）证实了几个代表性基因的表达。对差异表达基因的功能分析表明，与炎症和神经炎症反应相关的基因表达变化最为显著。我们进一步发现趋化因子CXCL1在大鼠DRG中的表达显著上调。对CXCL1的药理学阻断减少了蛋白激酶Cε的过量产生以及HP大鼠的痛觉过敏，但并未阻止DRG中GFAP的上调。这些结果表明神经炎症反应参与疼痛转变，可能是慢性疼痛的来源。DRG中的趋化因子CXCL1是HP模型大鼠慢性疼痛和疼痛转变的关键促成因素。因此，我们的研究为开发预防疼痛转变的有效疗法提供了一个假定的新靶点。
