Mesenchymal stem cells reduce the oxaliplatin-induced sensory neuropathy through the reestablishment of redox homeostasis in the spinal cord

Abstract

AimsThe present study was designed to investigate whether the antinociceptive effect of bone marrow-derived mesenchymal stem/stromal cells (MSC) during oxaliplatin (OXL)-induced sensory neuropathy is related to antioxidant properties. Main methodsMale mice C57BL/6 were submitted to repeated intravenous administration of OXL (1 mg/kg, 9 administrations). After the establishment of sensory neuropathy, mice were treated with a single intravenous administration of MSC (1 × 106), vehicle or gabapentin. Paw mechanical and thermal nociceptive thresholds were evaluated through von Frey filaments and cold plate test, respectively. Motor performance was evaluated in the rota-rod test. Gene expression profile, cytokine levels, and oxidative stress markers in the spinal cord were evaluated by real-time PCR, ELISA and biochemical assays, respectively. Key findingsOXL-treated mice presented behavioral signs of sensory neuropathy, such as mechanical allodynia and thermal hyperalgesia, which were completely reverted by a single administration of MSC. Repeated oral treatment with gabapentin (70 mg/kg) induced only transient antinociception. The IL-1β and TNF-α spinal levels did not differ between mice with or without sensory neuropathy. MSC increased the levels of anti-inflammatory cytokines, IL-10 and TGF-β, in the spinal cord of neuropathic mice, in addition to increasing the gene expression of antioxidant factors SOD and Nrf-2. Additionally, nitrite and MDA spinal levels were reduced by the MSC treatment. SignificanceMSC induce reversion of sensory neuropathy induced by OXL possibly by activation of anti-inflammatory and antioxidant pathways, leading to reestablishment of redox homeostasis in the spinal cord.