Abstract
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.
Highlights
Morphine is an opiate receptor agonist and analgesic that is routinely administered in cases of strong and chronic pain in clinics
Anakinra increased the analgesic effect of morphine (P < 0.05 to P < 0.001), and decreased the tolerance to morphine at a significant level (P < 0.05 to P < 0.001)
It decreased oxidative stress and endoplasmic reticulum (ER)-stress when given as a single-dose morphine and tolerance induction (P < 0.01 to P < 0.001)
Summary
Morphine is an opiate receptor agonist and analgesic that is routinely administered in cases of strong and chronic pain in clinics. The duration of morphine’s effect is reduced by the development of tolerance to its antinociceptive properties. Recent studies propose that an endogenous proinflammatory cytokine, especially interleukin 1 beta (IL-1 β), linked to the regulation of many physiological and pathological pathways, is involved in morphine analgesia and tolerance development [1,2,3]. Glia cells have important roles in facilitating pain by secreting proinflammatory cytokines, such as IL-1 [4]. Previous studies reported that it improves the clinical markers of rheumatoid arthritis (RA) at significant levels.
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