Aim:Nerve entrapment syndromes are the most common causes of neuropathic pain. Surgical decompression is preferred method of treatment. The goal of the study was to compare the efficacy of curcumin, tramadol and chronic constriction release treatment (CCR), individually or together, in a rat model of sciatic nerve injury.Material and Methods:Eighty male-rats were divided into eight study groups. Group 1 was the sham group. Group 2 was the control group with established chronic constriction injury (CCI). CCI was also established in Groups 3–8. Group 3 underwent chronic constriction release (CCR). Groups 4 and 5 received curcumin and tramadol. Groups 6 and 7 also received curcumin (100 mg kg-1 daily, oral) and tramadol (10 mg kg-1 daily, intraperitoneal, 14 days) after CCR, respectively. Combined curcumin-tramadol treatment was applied to Group 8. Behavioral tests (thermal hyperalgesia, dynamic plantar, cold plate test) were performed on days 0, 3, 7, 13, 17, and 21. Tissue tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) levels were analyzed in the nerve and dorsal root ganglion (DRG) samples on day 21.days. Histopathologic examination was performed on nervous tissue and DRG.Results:Tramadol-CCR and tramadol-curcumin significantly attenuated mechanical allodynia and thermal hyperalgesia. In CCI-CCR-tramadol treatment, TNF-α levels were found significantly lower in the sciatic nerve tissue and DRG, and IL-10 levels were significantly higher in the sciatic nerve tissue. Conclusion:CCI-CCR-tramadol treatment is highly effective in the symptomatic treatment of neuropathic pain. CCR-curcumin is associated with decreased degeneration and increased regeneration of the nerve tissue.