Pregabalin and lacosamide ameliorate paclitaxel-induced peripheral neuropathy via inhibition of JAK/STAT signaling pathway and Notch-1 receptor

Publication date: Available online 15 August 2018Source: Neurochemistry InternationalAuthor(s): Khaled F. Al-Massri, Lamiaa A. Ahmed, Hanan S. El-AbharAbstractAnticonvulsant 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 f...
Source: Neurochemistry International - Category: Neuroscience Source Type: research