Therapeutic Efficacy of Digoxin in Oxaliplatin and Chronic Constriction Injury Model of Neuropathic Pain in Rats

Abstract

Background: Neuropathic pain poses a considerable challenge in clinical practice, affecting a significant portion of the global population. Existing treatments often provide only symptomatic relief and are associated with limited efficacy and adverse effects, highlighting the need for novel therapeutic strategies. Methods: This study investigates the repurposing potential of digoxin for neuropathic pain management. Digoxin works as a soluble epoxide hydrolase (sEH) enzyme inhibitor, traditionally given for cardiac conditions. The neuropathic pain management (anti-nociceptive and anti-inflammatory role) of digoxin at 0.1 & 0.2 mg/kg was studied in a rat model having chronic constriction injury (CCI) and oxaliplatin-induced neuropathy. The reduction in pain was assessed through multiple behavioural assays like the acetone drop test, hot plate test, and pin-prick test. The mitochondrial functions, oxidative stress, & inflammation condition were estimated by biochemical analyses & gene expression studies of relevant markers. The histopathological examination depicts the morphology of tissue damage. Results: Digoxin administration attenuated neuropathic pain behaviour and reduced neuroinflammation in both CCI and oxaliplatin-induced models. Additionally, digoxin treatment significantly improved mitochondrial function and decreased oxidative stress levels in rat models. Histopathological analysis revealed a reduction in axonal damage in the sciatic nerve. Gene expression analysis indicates downregulation of pro-inflammatory markers such as tumor necrosis factor-α (TNF-α) and nuclear factor-kappa B (NF-κB). Conclusion: This study concludes that digoxin acts as a sEH inhibitor and holds promise for repurposing for neuropathic pain management.