Pioglitazone prevents morphine antinociception tolerance and withdrawal symptoms in rats

Ghavimi, Hamed; Hassanzadeh, Kambiz; Maleki‐Dizaji, Nasrin; Azarfardian, A.; Ghasami, Saeed; Zolali, Elmira; Charkhpour, Mohammad

doi:10.1007/s00210-014-0996-y

Cited by 21 publications

(18 citation statements)

References 47 publications

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“…No change was observed in the thalamus of the two groups of macaques. These findings are in keeping with the previous reports wherein morphine administered rats exhibited neuroinflammation in the cortex [84,85], nucleus accumbens [86], ventral tegmental area [87], and cerebellum [85], and decreased expression of proinflammatory cytokines in the rat hippocampus [88], and brain stem [86]. Interestingly, morphine-dependent animals exhibited increased proinflammatory cytokines expression in brain regions (frontal cortex, occipital cortex, cerebellum and basal ganglia) where the ER stress-mediated defective autophagy was predominant.…”

Section: Discussionsupporting

confidence: 93%

Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress-Autophagy Axis

et al. 2018

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A recent study from our lab has revealed a link between morphine-mediated autophagy and synaptic impairment. The current study was aimed at investigating whether morphine-mediated activation of astrocytes involved the ER stress/autophagy axis. Our in vitro findings demonstrated upregulation of GFAP indicating astrocyte activation with a concomitant increase in the production of proinflammatory cytokines in morphine-exposed human astrocytes. Using both pharmacological and gene-silencing approaches, it was demonstrated that morphine-mediated defective autophagy involved upstream activation of ER stress with subsequent downstream astrocyte activation via the μ-opioid receptor (MOR). In vivo validation demonstrated preferential activation of ER stress/autophagy axis in the areas of the brain not associated with pain such as the basal ganglia, frontal cortex, occipital cortex, and the cerebellum of morphine-dependent rhesus macaques, and this correlated with increased astrocyte activation and neuroinflammation. Interventions aimed at blocking either the MOR or ER stress could thus likely be developed as promising therapeutic targets for abrogating morphine-mediated astrocytosis.

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Section: Discussionsupporting

confidence: 93%

Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress-Autophagy Axis

et al. 2018

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“…The role of PPAR signalling in the development or modulation of other chronic pain conditions, such as osteoarthritis, cancer pain and migraine requires further study, as does the interaction of PPAR signalling with other well‐characterized endogenous pain control systems and currently prescribed analgesics. On this latter point, the PPARγ agonist pioglitazone has been shown to attenuate tolerance to morphine in a rat model of inflammatory pain (Ghavimi et al ., , Ghavimi et al ., ) and in the mouse tail immersion test (de Guglielmo et al ., ). Similar potential synergistic antinociceptive interactions with the cannabinoid (Russo et al ., ) and TRPV1 (Ambrosino et al ., ) signalling systems have been reported.…”

Section: Future Perspectivesmentioning

confidence: 99%

PPARs and pain

Okine

Gaspar

Finn

2018

British J Pharmacology

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Chronic pain is a common cause of disability worldwide and remains a global health and socio-economic challenge. Current analgesics are either ineffective in a significant proportion of patients with chronic pain or associated with significant adverse side effects. The PPARs, a family of nuclear hormone transcription factors, have emerged as important modulators of pain in preclinical studies and therefore a potential therapeutic target for the treatment of pain. Modulation of nociceptive processing by PPARs is likely to involve both transcription-dependent and transcription-independent mechanisms. This review presents a comprehensive overview of preclinical studies investigating the contribution of PPAR signalling to nociceptive processing in animal models of inflammatory and neuropathic pain. We examine current evidence from anatomical, molecular and pharmacological studies demonstrating a role for PPARs in pain control. We also discuss the limited evidence available from relevant clinical studies and identify areas that warrant further research.

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“…The rats in the saline group received only saline on the ninth day. One hour after the morning morphine injection on the ninth day, the rats received naloxone (4mg/kg) 27 intraperitoneally to induce the withdrawal signs. The rats were studied in a clear plexiglass chamber, and after naloxone injection, withdrawal signs were evaluated by an observer, who was not aware of the nature of the treatments received by animals, during a 60 minute period, and 11 distinct behaviors were recorded.…”

Section: Induction Of the Morphine Withdrawal And Measurement Of The mentioning

confidence: 99%

Evaluating the Effects of Chronic Administration of Natural Honey on the Development of Dependence on Morphine in the Male Rats

2019

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Background: According to the previous studies, the exact mechanism of dependence on opioids and withdrawal syndrome has not been fully understood but one of the most important mechanisms is the increase of pro-inflammatory cytokines in CNS. On the other way, previous studies showed that natural honey (NHO) has anti-inflammatory properties. This study was aimed to evaluate the effects of chronic administration of natural honey on the development of morphine dependence in male rats. Methods: Honey was prepared from Tarom Oliya region in Zanjan province. Experiments were performed on male Wistar rats weighing 225-275 g, randomly divided into 6 groups (n=8). The study groups included morphine group, the three doses of morphine plus honey group (at doses of 200,400 and 800 mg/kg, i.p.), the morphine plus vehicle group, and the saline group. The subcutaneous injections of additive doses of morphine were used for 9 days to create morphine dependency. On the 9th day, one hour after the morning dose of morphine, naloxone (4 mg/kg, i.p.) was injected, and symptoms of withdrawal syndrome were assessed for 60 minutes. Then, blood samples were taken to measure TNF-α. One-way ANOVA and Tukey tests were used to compare the results. P- Value of <0.05 was considered as statistically significant. Results: The results of this study showed that intraperitoneal injection of honey at 3 doses (200, 400 and 800 mg/kg with p <0.001) could significantly decrease the total score of the symptoms compared to the morphine-vehicle control group. Natural honey (NHO) could significantly decrease TNF-α at dose of 400 mg/kg. Conclusion: The results indicated that chronic administration of NHO had beneficial effects in reducing symptoms of morphine withdrawal syndrome, and this effect is probably due to the anti-inflammatory effect caused by the polyphenolic compounds in honey.<br />

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Pioglitazone prevents morphine antinociception tolerance and withdrawal symptoms in rats

Cited by 21 publications

References 47 publications

Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress-Autophagy Axis

Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress-Autophagy Axis

PPARs and pain

Evaluating the Effects of Chronic Administration of Natural Honey on the Development of Dependence on Morphine in the Male Rats

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