Dimethyl Fumarate Ameliorates Paclitaxel-Induced Neuropathic Pain in Rats

• Published in: Curēus (Palo Alto, CA) CA), 2022-09, Vol.14 (9), p.e28818-e28818
• Main Authors: Singh, Jagjit, Thapliyal, Surabhi, Kumar, Ashish, Paul, Pranoy, Kumar, Nitesh, Bisht, Manisha, Naithani, Manisha, Rao, Shalinee, Handu, Shailendra S
• Format: Article
• Language: English
• Subjects: Adenosine; Antioxidants; Cellulose; Chemotherapy; Cold; Cytokines; Drug dosages; Drug withdrawal; Enzymes; Experiments; Gene expression; Hyperalgesia; Kinases; Laboratory animals; Life Sciences; Multiple sclerosis; Neurology; Other; Pain; Pain Management; Peripheral neuropathy; Polymerase chain reaction; Proteins; Spinal cord; Tumor necrosis factor-TNF
• ISSN: 2168-8184; 2168-8184
• DOI: 10.7759/cureus.28818

BackgroundPaclitaxel (PTX)-induced peripheral neuropathy (PIPN) is nonresponsive to the currently available analgesics. Previous studies have shown the role of oxidative stress and central sensitization in the development of peripheral neuropathy. Dimethyl fumarate (DMF) acts as a nuclear factor erythroid-2-related factor 2 (Nrf2) activator with neuroprotective benefits and is approved for use in multiple sclerosis.Materials and methodsIn the current research, we evaluated the efficacy of DMF on paclitaxel-induced peripheral neuropathy in rats. Every alternate day for one week, paclitaxel 2 mg/kg dose was injected to establish a rat model of PIPN. Animals were treated with 25 mg/kg and 50 mg/kg of DMF. All the animals were assessed for thermal hyperalgesia, cold allodynia, and mechanical allodynia once a week. The gene expression of Nrf2 and the levels of pro-inflammatory mediators (interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and IL-1β) were quantified in the sciatic nerves of these rats. The levels of p38 mitogen-activated protein kinase (MAPK) and brain-derived neurotrophic factor (BDNF) were quantified in the dorsal horn of the spinal cord.ResultsDMF significantly attenuated paclitaxel-induced thermal hyperalgesia and cold/mechanical allodynia. A significant decrease in the levels of pro-inflammatory cytokines with the levels of p38 MAPK and BDNF was observed in the DMF-treated animals. DMF treatment significantly upregulated the gene expression of Nrf2 in the sciatic nerve.ConclusionThese findings suggest that DMF prevented the development of PIPN in rats through the activation of Nrf2 and the inhibition of p38 MAPK and BDNF.