Aim:Neuropathic pain can be caused by diabetes, nerve damage, postherpetic neuralgia, multiple sclerosis, and spinal cord injury, originating either in the peripheral or central nervous system. Several inflammatory mediators have a role in the pathogenesis of neuropathic pain. In this study, we evaluated the effects of tramadol on inflammation by measuring NLRP1 and IL-1 beta (IL-1β) levels in an experimental neuropathic pain model.Material and Methods:Sprague–Dawley rats were divided into three groups: control, chronic constriction injury (CCI), and CCI + tramadol. Neuropathic pain was assessed using mechanical allodynia, thermal hyperalgesia, and cold allodynia. IL-1β and NLRP1 levels were evaluated using ELISA on sciatic nerve (SN), dorsal root ganglion (DRG), and serum either on day 3 or days 8 postsurgery.Results:On day 3, paw withdrawal latency (PWL) was lower in the CCI and CCI + tramadol groups than the control group in both mechanical and cold allodynia tests. On day 8, the PWL in the CCI group was also lower than in the control group. In contrast, tramadol increased the PWL on day 8 compared to day 3 in the CCI group. During cold allodynia, PWL decreased in the CCI group, however, tramadol reversed this effect on days 3 and 8. Tramadol, therefore, ameliorated pain hypersensitivity in mechanical/cold allodynia tests. Serum IL-1β levels were higher in the CCI + tramadol and CCI groups than the control group, although serum IL-1β levels in the CCI and CCI + tramadol groups were comparable. Tramadol decreased the IL-1β and NLRP1 in DRG compared with the CCI group. A similar trend was observed in the SN samples.Conclusion:Our experiments revealed an increase in IL-1β and NLRP-1 levels in a neuropathic pain model and found that tramadol had an anti-inflammatory effect on the IL-1β and NLRP1 inflammasomes.