Original articleNrf2 and NF-κB modulation by Plumbagin attenuates functional, behavioural and biochemical deficits in rat model of neuropathic pain

- Antioxidants are beneficial in peripheral nerve injury induced neuropathic pain (NP).
- Oxidative stress and neuroinflammation play a critical role in pathogenesis of NP.
- Simultaneous regulation of Nrf-2 and NF-κB could attenuate NP.
- Plumbagin can be further evaluated for management of NP.

BackgroundPlumbagin is known to exhibit a broad range of biological activities including anti-cancer, antimicrobial and has been widely used traditionally. Nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) inhibitory and Nuclear factor (erythroid derived-2) like-2 (Nrf2) modulatory activities of Plumbagin have been reported already. In nerve injury model of neuropathy in rats, the role of NF-κB upregulation and declined antioxidant defence has been well recognized. So, we evaluated neuroprotective potential of Plumbagin in chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in male Sprague-Dawley rats.MethodsAnimals were tested for functional, behavioural and biochemical changes. Various markers associated with oxidative stress and inflammatory changes were assessed in the sciatic nerve and dorsal root ganglion (DRG) of the animals exposed to CCI mediated nerve injury.ResultsCCI induced nerve injury led to long-lasting mechanical hyperalgesia, loss of hind limb function and abnormal pain sensation. Plumbagin treatment (10 and 20 mg/kg, po) significantly and dose-dependently reversed mechanical hyperalgesia and other functional deficits. There was a marked increase in NF-κB and reduced Nrf2 levels in sciatic nerve and DRG following nerve injury. Plumbagin strengthened the antioxidant defence by improving Nrf2 levels and checked the neuroinflammation by decreasing NF-κB levels in sciatic nerve and DRG.ConclusionsTogether, these results suggested that Plumbagin alleviated CCI-induced neuropathic pain via antioxidant and anti-inflammatory mechanisms. Hence, the study suggests that Plumbagin may be useful for the management of trauma-induced neuropathic pain.

Schematic diagram predicting the possible effects of Plumbagin against CCI induced neuropathy and neuropathic pain.100