Anticonvulsant drugs such as pregabalin (PGB) and lacosamide (LCM), exhibit potent analgesic effects in diabetic neuropathy; however, their possible role/mechanisms in paclitaxel (PTX)-induced peripheral neuropathy have not been elucidated, which is the aim of the present study. Neuropathic pain was induced in rats by injecting PTX (2 mg/kg, i. p) on days 0, 2, 4 and 6. Forty eight hours after the last dose of PTX, rats were treated orally with 30 mg/kg/day of either PGB or LCM for 21 days. Both therapies improved thermal hyperalgesia and cold allodynia induced by PTX. Interestingly, LCM therapy showed no motor impairment that was observed upon using PGB, as demonstrated using rotarod test. Treatment with PGB or LCM restored the sciatic nerve content of the depleted total antioxidant capacity (TAC) and nerve growth factor (NGF), and lessened the elevated contents of nuclear factor kappa B p65 (NF-kB p65), tumor necrosis factor-α (TNF-α), and active caspase-3. On the molecular level, the drugs reduced the protein expression of Notch1 receptor, phosphorylated p38 mitogen-activated protein kinase (p-p38-MAPK), and the trajectory interleukin-6/phosphorylated janus kinase 2/phosphorylated signal transducer and activator of transcription 3 (IL-6/p-JAK2/p-STAT3). Therefore, the current study demonstrated a pivotal role for LCM in the management of PTX-induced peripheral neuropathy similar to PGB, but without motor adverse effects via the inhibition of oxidative stress, inflammation and apoptosis, as well as IL-6/JAK/STAT pathway and Notch1 receptor over-expression.

普瑞巴林（PGB）和拉考酰胺（LCM）等抗惊厥药在糖尿病性神经病中表现出有效的镇痛作用。然而，尚未阐明它们在紫杉醇（PTX）引起的周围神经病中的可能作用/机制，这是本研究的目的。通过在第0、2、4和6天注射PTX（2 mg / kg，i。p）在大鼠中诱发神经性疼痛。在最后一次服用PTX后48小时，大鼠口服30 mg / kg /天PGB或LCM为21天。两种疗法均能改善PTX引起的热痛觉过敏和冷异常性疼痛。有趣的是，LCM治疗未显示使用PGB时观察到的运动障碍，如使用旋转脚踏试验所证明的。用PGB或LCM治疗可恢复坐骨神经的总抗氧化剂能力（TAC）和神经生长因子（NGF）减少，并减少了核因子κBp65（NF-kB p65），肿瘤坏死因子-α（TNF-α）和活性caspase-3含量的升高。在分子水平上，这些药物降低了Notch1受体（磷酸化的p38丝裂原活化蛋白激酶）的蛋白表达（p -p38-MAPK），以及轨迹白介素6 /磷酸化的janus激酶2 /磷酸化的信号转导子和转录激活子3（IL-6 / p -JAK2 / p -STAT3）。因此，当前的研究表明LCM在PTX诱导的周围神经病变的治疗中起着关键作用，类似于PGB，但没有通过抑制氧化应激，炎症和细胞凋亡以及IL-6 / JAK / STAT而产生运动不良反应通路和Notch1受体过表达。