Modulatory effect of mesenchymal stem cells on pregabalin and lacosamide in paclitaxel-induced neuropathic pain in rats / Khaled Faisal Abed Elsalam Amassri ; Supervised Hanan Salah Eldin Elabhar , Lamiaa Ahmed Ahmed Attia

Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Peripheral neuropathy is a common adverse effect observed during the use of paclitaxel (PTX) as chemotherapy. The present investigation was directed to estimate the possible neuroprotective effect of pregabalin (PGB) and lacosamide (LCM) in PTX-induced peripheral neuropathy and the modulatory role of bone marrow-derived mesenchymal stem cells (BM-MSCs) on these treatments. 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 PGB (30 mg/kg/day) and LCM (30 mg/kg/day) for 21 days with or without a single intravenous administration of BM-MSCs. All therapies improved thermal hyperalgesia and cold allodynia induced by PTX. Interestingly, BM-MSCs therapy effectively prevented motor impairment observed by PGB treatment as demonstrated using rotarod test. Treatment with PGB, LCM and BM-MSCs 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-mB p65), tumor necrosis factor-Ü (TNF-Ü), and active caspase-3. On the molecular level, all therapies reduced the protein expression of Notch1 receptor, phosphorylated p38 mitogen-activated protein kinase (p-p38-MAPK), and the interleukin-6/phosphorylated Janus kinase 2/phosphorylated signal transducer and activator of transcription 3 (IL-6/p-JAK2/p-STAT3) trajectory

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