LAUSR

HIGHLIGHTSPTX caused neuronal oxidative stress, inflammation and apoptosis.PTX activated Notch 1 receptor and JAK/STAT signal pathway.PGB and/or BM‐MSCs treatments alleviated peripheral neuropathy evoked by PTX.BM‐MSCs with PGB improved motor dysfunction induced by PGB therapy alone.BM‐MSCs with PGB provided an additional benefit compared to PGB therapy alone. ABSTRACT Peripheral neuropathy is a common adverse effect observed during the use of paclitaxel (PTX) as chemotherapy. The present investigation was directed to estimate the modulatory effect of bone marrow derived mesenchymal stem cells (BM‐MSCs) on pregabalin (PGB) treatment in PTX‐induced peripheral neuropathy. Neuropathic pain was induced in rats by injecting PTX (2 mg/kg, i.p) 4 times every other day. Rats were then treated with PGB (30 mg/kg/day, p.o.) for 21 days with or without a single intravenous administration of BM‐MSCs. At the end of experiment, behavioral and motor abnormalities were assessed. Animals were then sacrificed for measurement of total antioxidant capacity (TAC), nerve growth factor (NGF), nuclear factor kappa B p65 (NF‐&kgr;B p65), tumor necrosis factor‐alpha (TNF‐&agr;), interleukin‐6 (IL‐6), and active caspase‐3 in the sciatic nerve. Moreover, protein expressions of Notch1 receptor, phosphorylated Janus kinase 2 (p‐JAK2), phosphorylated signal transducer and activator of transcription 3 (p‐STAT3), and phosphorylated p38 mitogen‐activated protein kinase (p‐p38‐MAPK) were estimated. Finally, histological examinations were performed to assess severity of sciatic nerve damage and for estimation of BM‐MSCs homing. Combined PGB/BM‐MSCs therapy provided an additional improvement toward reducing PTX‐induced oxidative stress, neuro‐inflammation, and apoptotic markers. Interestingly, BM‐MSCs therapy effectively prevented motor impairment observed by PGB treatment. Combined therapy also induced a significant increase in cell homing and prevented PTX‐induced sciatic nerve damage in histological examination. The present study highlights a significant role for BM‐MSCs in enhancing treatment potential of PGB and reducing its motor side effects when used as therapy in the management of peripheral neuropathy.