Anakinra, an interleukin-1 receptor antagonist, increases the morphine analgesic effect and decreases morphine tolerance development by modulating oxidative stress and endoplasmic reticulum stress in rats
Turk J Med Sci
; 50(8): 2048-2058, 2020 12 17.
Article
em En
| MEDLINE
| ID: mdl-32659878
ABSTRACT
Background/aim:
Recent 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-1ß's biological activity by avoiding signal transduction. In this study, we aimed to examine the effects of anakinra on morphine analgesia and tolerance. Materials andmethods:
In this study, 36 Wistar Albino (230250 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.Results:
Anakinra 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).Conclusion:
Anakinra 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dor
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Estresse Oxidativo
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Tolerância a Medicamentos
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Proteína Antagonista do Receptor de Interleucina 1
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Estresse do Retículo Endoplasmático
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Analgésicos Opioides
/
Morfina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Turk J Med Sci
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Turquia
País de publicação:
TR
/
TURKEY
/
TURQUIA