Pharmazentrum Frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor Stern-Kai 7, 60590 Frankfurt am Main, Germany.
Cells. 2022 Jun 19;11(12):1967. doi: 10.3390/cells11121967.
(1) AlphαSynuclein (αSyn) is a synaptic protein which is expressed in the nervous system and has been linked to neurodegenerative diseases, in particular Parkinson's disease (PD). Symptoms of PD are mainly due to overexpression and aggregation of αSyn and include pain. However, the interconnection of αSyn and pain has not been clarified so far. (2) We investigated the potential effects of a αSyn knock-out on the nociceptive behaviour in mouse models of acute, inflammatory and neuropathic pain. Furthermore, we assessed the impact of αSyn deletion on pain-related cellular and molecular mechanisms in the spinal cord in these models. (3) Our results showed a reduction of acute cold nociception in αSyn knock-out mice while responses to acute heat and mechanical noxious stimulation were similar in wild type and knock-out mice. Inflammatory nociception was not affected by αSyn knock-out which is also mirrored by unaltered inflammatory gene expression. In contrast, in the SNI model of neuropathic pain, αSyn knock-out mice showed decreased mechanical allodynia as compared to wild type mice. This effect was associated with reduced proinflammatory mechanisms and suppressed activation of MAP kinase signalling in the spinal cord while endogenous antinociceptive mechanisms are not inhibited. (4) Our data indicate that αSyn plays a role in neuropathy and its inhibition might be useful to ameliorate pain symptoms after nerve injury.
(1) α-突触核蛋白（αSyn）是一种突触蛋白，在神经系统中表达，与神经退行性疾病有关，特别是帕金森病（PD）。PD 的症状主要是由于 αSyn 的过度表达和聚集，包括疼痛。然而，αSyn 和疼痛之间的联系尚未得到阐明。(2) 我们研究了αSyn 敲除对急性、炎症和神经病理性疼痛小鼠模型中痛觉行为的潜在影响。此外，我们评估了在这些模型中，αSyn 缺失对脊髓中与疼痛相关的细胞和分子机制的影响。(3) 我们的结果表明，αSyn 敲除小鼠的急性冷觉痛觉降低，而对急性热觉和机械性伤害性刺激的反应在野生型和敲除型小鼠中相似。αSyn 敲除对炎症性疼痛没有影响，这也反映在炎症基因表达没有改变。相比之下，在 SNI 神经病理性疼痛模型中，与野生型小鼠相比，αSyn 敲除小鼠的机械性触诱发痛降低。这种效应与脊髓中促炎机制减少和 MAP 激酶信号通路激活受到抑制有关，而内源性抗伤害机制不受抑制。(4) 我们的数据表明，αSyn 在神经病变中起作用，其抑制可能有助于改善神经损伤后的疼痛症状。
