The First Affiliated Hospital of Jinan University, Guangzhou, China; Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China.
Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China.
Neurotherapeutics. 2024 Sep;21(5):e00383. doi: 10.1016/j.neurot.2024.e00383. Epub 2024 Jul 2.
Neuropathic pain (NP), a severe chronic pain condition, remains a substantial clinical challenge due to its complex pathophysiology and limited effective treatments. An association between the members of the Fibroblast Growth Factors (FGFs), particularly Fgf3, and the development of NP has become evident. In this study, utilizing a mouse model of NP, we observed a time-dependent increase in Fgf3 expression at both mRNA and protein levels within the dorsal root ganglia (DRG). Functional studies revealed that blocking Fgf3 expression mitigated nerve injury induced nociceptive hypersensitivity, suggesting its pivotal role in pain modulation. Moreover, our findings elucidate that Fgf3 contributes to pain hypersensitivity through the activation of the Akt/mTOR signaling in injured DRG neurons. These results not only shed light on the involvement of Fgf3 in nerve injury-induced NP but also highlight its potential as a promising therapeutic target for pain management. This study thereby advances our understanding of the molecular mechanisms underlying NP and opens new avenues for the development of effective treatment strategies.
神经病理性疼痛(NP)是一种严重的慢性疼痛病症,由于其复杂的病理生理学和有限的有效治疗方法,仍然是一个重大的临床挑战。成纤维细胞生长因子(FGFs)成员之间的关联,特别是 Fgf3,与 NP 的发展已经变得明显。在这项研究中,我们利用 NP 的小鼠模型,观察到在背根神经节(DRG)中 Fgf3 表达在 mRNA 和蛋白质水平上的时间依赖性增加。功能研究表明,阻断 Fgf3 表达减轻了神经损伤引起的痛觉过敏,表明其在疼痛调节中的关键作用。此外,我们的研究结果表明,Fgf3 通过激活损伤的 DRG 神经元中的 Akt/mTOR 信号通路导致疼痛过敏。这些结果不仅阐明了 Fgf3 在神经损伤引起的 NP 中的作用,而且还突出了它作为疼痛管理有希望的治疗靶点的潜力。因此,这项研究加深了我们对 NP 分子机制的理解,并为开发有效的治疗策略开辟了新的途径。