Carta Giacomo, Fornasari Benedetta Elena, Fregnan Federica, Ronchi Giulia, De Zanet Stefano, Muratori Luisa, Nato Giulia, Fogli Marco, Gambarotta Giovanna, Geuna Stefano, Raimondo Stefania
Department of Clinical and Biological Sciences, University of Torino, 10043 Torino, Italy.
Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Torino, 10043 Torino, Italy.
Biomedicines. 2022 May 31;10(6):1296. doi: 10.3390/biomedicines10061296.
Somatic nerve injuries are a rising problem leading to disability associated with neuropathic pain commonly reported as mechanical allodynia (MA) and hyperalgesia. These symptoms are strongly dependent on specific processes in the dorsal root ganglia (DRG). Neurodynamic treatment (NDT), consisting of selective uniaxial nerve repeated tension protocols, effectively reduces pain and disability in neuropathic pain patients even though the biological mechanisms remain poorly characterized. We aimed to define, both in vivo and ex vivo, how NDT could promote nerve regeneration and modulate some processes in the DRG linked to MA and hyperalgesia.
We examined in Wistar rats, after unilateral median and ulnar nerve crush, the therapeutic effects of NDT and the possible protective effects of NDT administered for 10 days before the injury. We adopted an ex vivo model of DRG organotypic explant subjected to NDT to explore the selective effects on DRG cells.
Behavioural tests, morphological and morphometrical analyses, and gene and protein expression analyses were performed, and these tests revealed that NDT promotes nerve regeneration processes, speeds up sensory motor recovery, and modulates mechanical pain by affecting, in the DRG, the expression of TACAN, a mechanosensitive receptor shared between humans and rats responsible for MA and hyperalgesia. The ex vivo experiments have shown that NDT increases neurite regrowth and confirmed the modulation of TACAN.
The results obtained in this study on the biological and molecular mechanisms induced by NDT will allow the exploration, in future clinical trials, of its efficacy in different conditions of neuropathic pain.
躯体神经损伤问题日益严重,常导致与神经性疼痛相关的残疾,神经性疼痛通常表现为机械性异常性疼痛(MA)和痛觉过敏。这些症状在很大程度上依赖于背根神经节(DRG)中的特定过程。神经动力治疗(NDT),包括选择性单轴神经反复拉伸方案,尽管其生物学机制仍不清楚,但能有效减轻神经性疼痛患者的疼痛和残疾。我们旨在通过体内和体外实验确定NDT如何促进神经再生,并调节DRG中与MA和痛觉过敏相关的一些过程。
我们在Wistar大鼠单侧正中神经和尺神经挤压伤后,研究了NDT的治疗效果以及在损伤前10天给予NDT的可能保护作用。我们采用了对DRG器官型外植体进行NDT处理的体外模型,以探索对DRG细胞的选择性作用。
进行了行为测试、形态学和形态计量学分析以及基因和蛋白质表达分析,这些测试表明NDT促进神经再生过程,加速感觉运动恢复,并通过影响DRG中TACAN的表达来调节机械性疼痛,TACAN是人与大鼠共有的一种机械敏感受体,负责MA和痛觉过敏。体外实验表明NDT增加了神经突再生并证实了对TACAN的调节作用。
本研究中关于NDT诱导的生物学和分子机制的结果,将有助于在未来的临床试验中探索其在不同神经性疼痛情况下的疗效。