The Effect of Anakinra on Paclitaxel-Induced Peripheral Neuropathic Pain in Rats.

Objective: Paclitaxel is used in the treatment of cancer, and it may cause interleukin-1 beta (IL-1β)-related peripheral neuropathic pain. While our primary aim was to investigate the analgesic efficacy of an IL-1β antagonist, a secondary outcome was to assess whether a correlation exists between analgesic effects and antioxidant activity.

Methods: A total of 24 albino Wistar male rats were divided into the following groups: paclitaxel-control, paclitaxel+50 mg kg anakinra, paclitaxel+100 mg kg anakinra and healthy group (HG). After the normal paw pain threshold in all animal groups was measured using a Basile algesimeter, a single dose of 2 mg kg paclitaxel was intraperitoneally administered on the 1, 3, 5 and 7 days. Anakinra was intraperitoneally administered following the final paclitaxel administration. The paw pain thresholds in the groups were measured before and seven days after paclitaxel administration and at the 1 and 3 hours after anakinra administration. After the third hour of measurement, the rats were killed with high doses of ketamine, and the paw tissues were removed. Malondialdehyde, myeloperoxidase and total glutathione levels were measured in claw tissues, and IL-1β gene expression was determined. The biochemical results were compared with the results of the HG; in the meanwhile the claw pain threshold results were compared with the results obtained after the last paclitaxel and the results obtained from the 1 and 3 hours after the anakinra application.

Results: The claw paw pain threshold of the rats decreased one and three hours after anakinra administration. Further, 100 mg kg anakinra had greater analgesic activity than 50 mg kg anakinra. A correlation was found between the antioxidant and analgesic activities of 100 mg kg anakinra.

Conclusion: Anakinra may be useful to reduce paclitaxel-induced neuropathic pain; further, 100 mg kg anakinra may have greater analgesic and antioxidant activities.