• Turk J Med Sci · Dec 2020

    Anakinra, an interleukin-1 receptor antagonist, increases morphine analgesic effect and decreases morphine tolerance development by modulating oxidative stress and endoplasmic reticulum stress in rats.

    • Onur Avcı and Ahmet Şevki Taşkıran.
    • Department of Anesthesiology and Reanimation, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkey
    • Turk J Med Sci. 2020 Dec 17; 50 (8): 204820582048-2058.

    Background/AimRecent studies have shown that inflammation plays a role in morphine analgesia and tolerance development. Anakinra is a competitive inhibitor of IL-1 receptors and an antiinflammatory protein regulating IL-1β’s biological activity by avoiding signal transduction. In this study, we aimed to examine the effects of anakinra on morphine analgesia and tolerance.Materials And MethodsIn this study, 36 Wistar Albino (230–250 g) male rats were used. Animals were divided into 6 groups: saline (S), 100 mg/kg anakinra (A), 5mg/kg morphine (M), M+A, morphine tolerance (MT), and MT+A. The resulting analgesic effect was measured with hot plate and tail-flick analgesia tests. After the analgesia tests, the dorsal root ganglions (DRG) tissues were removed. Oxidative stress parameters [total antioxidant status (TAS), total oxidant status (TOS)], endoplasmic reticulum (ER) stress, and apoptosis proteins [E74-like factor 2 (elF-2α), activating transcription factor 4 (ATF-4), C/EBP homologous protein (CHOP), caspase-3, and bcl-2-associated X protein (bax)] were measured in DRG tissues.ResultsAnakinra showed an antinociceptive effect when given alone (P < 0.001). In addition, anakinra increased the analgesic effect of morphine (P < 0.05 to P < 0.001), and also decreased the tolerance to morphine at a significant level (P < 0.05 to P < 0.001). Moreover, it decreased oxidative stress and ER-stress when given as a single-dose morphine and tolerance induction (P < 0.01 to P < 0.001). Furthermore, anakinra decreased apoptosis proteins after tolerance development (P < 0.001).ConclusionAnakinra has antinociceptive properties, and it increases the analgesic effect of morphine and also prevents tolerance development. These effects probably occur by the modulation of oxidative stress and ER-stress pathways.This work is licensed under a Creative Commons Attribution 4.0 International License.

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