Co-administration of ibuprofen and L-carnosine ameliorates neuropathic pain and inflammatory changes in a rat model of chronic constriction injury

This study evaluated the anti-inflammatory mechanisms involved in antinociceptive effect of co-administration of Ibuprofen and L-carnosine in chronic constriction injury (CCI)-induced peripheral neuropathy in male Wistar rats. Fifty six male Wistar rats were randomly divided into seven groups ( n = 8): 1: Unligated vehicle-treated, 2: Sham-operated, 3: CCI vehicle-treated, 4: Ibuprofen (30 mg/kg) pretreatment + CCI, 5: Ibuprofen (30 mg/kg) pretreatment + L-carnosine (100 mg/kg) pretreatment + CCI, 6: CCI + Ibuprofen (30 mg/kg) post-treatment, 7: CCI + Ibuprofen (30 mg/kg) post-treatment + L-carnosine (100 mg/kg) post-treatment. Hyperalgesia and allodynia were assessed using hotplate and von Frey tests, respectively. After twenty-one days of treatment, spinal cord cytokines levels were evaluated. Possible structural alterations in sciatic nerve were histopathologically examined. Ibuprofen and L-carnosine alone and co-administered as pre- or post-treatment significantly reduced CCI-induced mechanical, thermal and cold hypersensitivity ( P < 0.05). CCI increased spinal NF-κB, TNF-α, IL-1β, and Ca²⁺ levels ( P < 0.05). These elevations were reduced by pre-treatment, specifically the co-administration, while post-treatment mainly reduced the TNF-α and IL-1β concentrations. Histology revealed comparatively well-preserved tissue architecture after treatment. Overall, ibuprofen and L-carnosine reduced CCI-induced neuropathic pain and neuroinflammatory changes, suggesting their possible therapeutic approaches for neuropathic pain.