Abstract
BackgroundChronic neuropathic pain syndrome is associated with impaired quality of life and is poorly manageable. Alpha lipoic acid (ALA) is a powerful antioxidant and showed its effectiveness on diabetic neuropathy and other acute peripheral nerve injuries but it was not evaluated in the chronic neuropathic pain, chronic constriction injury (CCI) in rat model by using duloxetine (DLX) as standard.MethodologyThe main objective of the study was to expedite ALA effect on chronic peripheral neuropathy induced by CCI of sciatic nerve in rats. In this study, male Wister rats were randomly divided into six groups (n = 8) including, normal saline, sham operated, surgery control, DLX 30mg/kg treated, ALA treated 25mg/kg, and ALA+DLX. The CCI of sciatic nerve was conducted on all animals except normal saline group and studied for 21 days (i.e. 14 days treatment period & 7 days treatment free period) by using different behavioral, biochemical and, histopathology studies.ResultsALA showed minor but significant decrease of thermal hyperalgesia, cold allodynia, malondialdehyde (MDA), total protein, lipid peroxidation, and nitric oxide levels and significant increase of motor coordination, glutathione level and decreased axonal degeneration significantly. These effects sustained even during treatment free period. ALA enhanced the effect of DLX when given in combination by showing sustained effect. In conclusion, ALA acted as potent antioxidant may be this activity is responsible for the potent neuroprotective effect.ConclusionHence, ALA attenuated the nueroinflammation mediated by chronic peripheral neuropathy. Further studies are warranted with ALA to develop as a clinically relevant therapeutic agent for the treatment of neuropathic pain.
Highlights
Neuropathic pain is due to the pain caused by lesion and/or disease of the somatosensory neurons [1]
In animals subjected to constriction injury (CCI), surgery control group there was a significant increase in protein level on 15th day and 22nd day compared to saline treated group
In animals subjected to CCI, surgery control group showed significant decrease in glutathione levels on 15th day compared to normal group, whereas the groups with Surgery control (SC), DLX, and DLA + Alpha lipoic acid (ALA) showed significant increase from 0.0140 ± 0.002 to 0.043 ± 0.003 and 0.086 ± 0.002 mM respectively in glutathione levels on 15th day compared to surgery control
Summary
Neuropathic pain is due to the pain caused by lesion and/or disease of the somatosensory neurons [1]. The animal models plays important role to explain the mechanisms responsible for the neuropathic pain [9]. The animal models of neuropathic pain describes that the hyperalgesia is related to the inflammatory response and inflammatory mediators are elevated in hyperalgesia in nerve injured rat models [10, 11]. The research studies explain that both peripheral and central mechanism(s) are involved in pathogenesis of neuropathic pain [12, 13]. Alpha lipoic acid (ALA) is a powerful antioxidant and showed its effectiveness on diabetic neuropathy and other acute peripheral nerve injuries but it was not evaluated in the chronic neuropathic pain, chronic constriction injury (CCI) in rat model by using duloxetine (DLX) as standard
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