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Role of NMDA receptors blockade in the thalamic paraventricular nucleus in morphine dependent rat model of formalin-induced pain

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Abstract

Evidence shows that the N-methyl-d-aspartate (NMDA) antagonist MK801 reduces the development of morphine (Mor) tolerance. The paraventricular nucleus of the thalamus (PVT) comprises the highest levels of μ-opioid receptors in the thalamus and is involved in pain modulation. The present study examined whether blocking NMDA receptors by administration of MK801 in the PVT nucleus could affect the nociceptive behavioral manifestations caused by the formalin in Mor-dependent rats. Male Wistar rats weighing 250–300 g were dependent on Mor by subcutaneously (s.c.) injection (6, 16, 26, 36, 46, 56, and 66 mg/kg, 2 ml/kg) at an interval of 24 h for 7 days. Animals were randomized into four experimental groups in which the NMDA receptor antagonist, MK801 (20 mM in 0.1 ml), or its vehicle were injected into the PVT nucleus for 7 days before each Mor injection. On day 8, the formalin test was carried out. Results showed that repetitive Mor administration prompted antinociception in interphase and phase II of formalin test. Also, inhibition of NMDA receptors decreased formalin-induced nociceptive behaviors in all phases of the test in Mor-dependent rats. Our findings suggested that continuous co-administration of MK801 into PVT with Mor could enhance the antinociceptive effect of Mor and reduce the nociceptive behaviors prompted by formalin in Mor-dependent rats.

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Acknowledgements

This work is supported by the Neuroscience Research Center of the Iran University of Medical Sciences.

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Authors and Affiliations

  1. Department of Microbiology, Karaj Branch Islamic Azad University, Karaj, Iran

    Fatemeh Samani & Mona Farhadi

  2. Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran

    Masoumeh Kourosh Arami

  3. Department of Neuroscience, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran

    Masoumeh Kourosh Arami

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  1. Fatemeh Samani
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  2. Masoumeh Kourosh Arami
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  3. Mona Farhadi
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Contributions

FS, MKA, and MF were responsible for the study concept and design. FS performed the experiments. MKA was responsible for provision of study materials and equipment, study validation, and supervision. MKA and MF assisted with data analysis and interpretation of findings. MKA drafted the manuscript. All authors critically reviewed content and approved final version for publication.

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Correspondence to Masoumeh Kourosh Arami.

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Samani, F., Arami, M.K. & Farhadi, M. Role of NMDA receptors blockade in the thalamic paraventricular nucleus in morphine dependent rat model of formalin-induced pain. Neurosci Behav Physi 53, 670–677 (2023). https://doi.org/10.1007/s11055-023-01343-6

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  • DOI: https://doi.org/10.1007/s11055-023-01343-6

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