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The Pronociceptive Effect of Paradoxical Sleep Deprivation in Rats: Evidence for a Role of Descending Pain Modulation Mechanisms

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Abstract

The mechanisms underlying the pronociceptive effect of paradoxical sleep deprivation (PSD) are not known. In this study, we asked whether PSD increases tonic nociception in the formalin test, decreases the antinociceptive effect of morphine administered into the periaqueductal gray matter (PAG), and disrupts endogenous descending pain modulation. PSD for either 24 or 48 h significantly increased formalin-induced nociception and decreased mechanical nociceptive paw withdrawal threshold. The maximal antinociceptive effect induced by morphine (0.9–9 nmol, intra-PAG) was significantly decreased by PSD. The administration of a low dose of the GABAA receptor antagonist, bicuculline (30–300 pmol, intra-PAG), decreased nociception in control rats, but not in paradoxical-sleep-deprived ones. Furthermore, the administration of the cholecystokinin (CCK) 2 receptor antagonist, YM022 (0.5–2 pmol) in the rostral ventral medulla (RVM), decreased nociception in paradoxical-sleep-deprived rats but not in control ones. While a dose of the CCK 2 receptor agonist, CCK-8 (8–24 pmol intra-RVM), increased nociception in control rats, but not in paradoxical-sleep-deprived ones. In addition, the injection of lidocaine (QX-314, 2 %, intra-RVM) decreased nociception in sleep-deprived rats, but not in control rats, while the lesion of the dorsolateral funiculus prevented the pronociceptive effect of PSD. Finally, PSD significantly increased c-Fos expression in the RVM. Therefore, PSD increases pain independently of its duration or of the characteristic of the nociceptive stimulus and decreases morphine analgesia at the PAG. PSD appears to increase pain by decreasing descending pain inhibitory activity and by increasing descending pain facilitatory activity.

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Acknowledgments

This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil. D.H.T was a recipient of a Master of Science fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)—Brazil. G.T. is a recipient of a PhD fellowship from CAPES. M.M.S.L. is a recipient of a research fellowship from CNPq.

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  1. Department of Physiology, Division of Biological Sciences, Federal University of Parana, Curitiba, Parana, Brazil

    Dabna H. Tomim, Felipe M. Pontarolla, Jessica F. Bertolini, Mauricio Arase, Glaucia Tobaldini, Marcelo M. S. Lima & Luana Fischer

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  1. Dabna H. Tomim
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Tomim, D.H., Pontarolla, F.M., Bertolini, J.F. et al. The Pronociceptive Effect of Paradoxical Sleep Deprivation in Rats: Evidence for a Role of Descending Pain Modulation Mechanisms. Mol Neurobiol 53, 1706–1717 (2016). https://doi.org/10.1007/s12035-014-9059-0

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