Pacini Alessandra, Tomassoni Daniele, Trallori Elena, Micheli Laura, Amenta Francesco, Ghelardini Carla, Di Cesare Mannelli Lorenzo, Traini Enea
Department of Experimental and Clinical Medicine, Anatomy and Histology Section, University of Florence, Florence, Italy.
School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy.
Front Pharmacol. 2021 Feb 24;12:607572. doi: 10.3389/fphar.2021.607572. eCollection 2021.
Peripheral neuropathies, characterized by altered nociceptive and muscular functions, are related to oxidative stress. Thioctic acid is a natural antioxidant existing as two optical isomers, but most clinically used as racemic mixture. The present study investigated the central nervous system's changes which followed loose-ligation-derived compression of sciatic nerve, the putative neuroprotective role of thioctic acid and the pain-alleviating effect on low-back pain suffering patients. Loose ligation of the right sciatic nerve was performed in spontaneously hypertensive rats (SHR), a model of increased oxidative stress, and in normotensive Wistar-Kyoto rats (WKY). Animals with sciatic nerve ligation were left untreated or were treated intraperitoneally for 15 days with 250 μmol·kg·die of (+/-)-thioctic acid; 125 μmol·kg·die of (+/-)-thioctic acid; 125 μmol·kg·die of (+)-thioctic acid lysine salt; 125 μmol·kg·die of (-)-thioctic acid; 300 μmol·kg·die pregabalin. Control SHR and WKY rats received the same amounts of vehicle. The clinical trial NESTIORADE (Sensory-Motor Neuropathies of the Sciatic Nerve: Comparative evaluation of the effect of racemic and dextro-rotatory forms of thioctic acid) examined 100 patients (49 males and 51 females aged 53 ± 11 years) dividing them into two equal-numbered groups, each treated daily for 60 days with 600 mg of (+/-)-thioctic acid or (+)-thioctic acid, respectively. The trial was registered prior to patient enrollment at EudraCT website (OSSC Number: 2011-000964-81). In the preclinical study, (+)-thioctic acid was more active than (+/-)- or (-)-enantiomers in relieving pain and protecting peripheral nerve as well as in reducing oxidative stress and astrogliosis in the spinal cord. Main findings of NESTIORADE clinical trial showed a greater influence on painful symptomatology, a quicker recovery and a better impact on quality of life of (+)-thioctic acid vs. (+/-)-thioctic acid. These data may have a pharmacological and pharmacoeconomical relevance and suggest that thioctic acid, above all (+)-enantiomer, could be considered for treatment of low-back pain involving neuropathy.
以伤害性感受和肌肉功能改变为特征的周围神经病变与氧化应激有关。硫辛酸是一种天然抗氧化剂，以两种旋光异构体形式存在，但临床上大多使用外消旋混合物。本研究调查了坐骨神经松弛结扎所致压迫后中枢神经系统的变化、硫辛酸可能的神经保护作用以及对下腰痛患者的镇痛效果。在自发性高血压大鼠（SHR，一种氧化应激增加的模型）和正常血压的Wistar-Kyoto大鼠（WKY）中对右侧坐骨神经进行松弛结扎。坐骨神经结扎的动物不进行治疗或腹腔注射250 μmol·kg·d的（±）-硫辛酸、125 μmol·kg·d的（±）-硫辛酸、125 μmol·kg·d的（+）-硫辛酸赖氨酸盐、125 μmol·kg·d的（-）-硫辛酸、300 μmol·kg·d的普瑞巴林，持续15天；对照的SHR和WKY大鼠接受等量的赋形剂。NESTIORADE临床试验（坐骨神经感觉运动神经病变：硫辛酸外消旋体和右旋体效果的比较评估）检查了100例患者（49例男性和
