Hyporesponsivity to mu-opioid receptor agonism in the Wistar-Kyoto rat model of altered nociceptive responding associated with negative affective state.

Autor:	Ferdousi MI; Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, Galway, Ireland.; Physiology, School of Medicine, National University of Ireland Galway, Galway, Ireland., Calcagno P; Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, Galway, Ireland.; Centre for Pain Research and Galway Neuroscience Centre, National University of Ireland Galway, Galway, Ireland.; Physiology, School of Medicine, National University of Ireland Galway, Galway, Ireland., Clarke M; Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, Galway, Ireland.; Centre for Pain Research and Galway Neuroscience Centre, National University of Ireland Galway, Galway, Ireland.; Physiology, School of Medicine, National University of Ireland Galway, Galway, Ireland., Aggarwal S; Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, Galway, Ireland.; Centre for Pain Research and Galway Neuroscience Centre, National University of Ireland Galway, Galway, Ireland.; Physiology, School of Medicine, National University of Ireland Galway, Galway, Ireland., Sanchez C; Alkermes Inc, Waltham, MA, United States., Smith KL; Alkermes Inc, Waltham, MA, United States., Eyerman DJ; Alkermes Inc, Waltham, MA, United States., Kelly JP; Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, Galway, Ireland.; Physiology, School of Medicine, National University of Ireland Galway, Galway, Ireland., Roche M; Centre for Pain Research and Galway Neuroscience Centre, National University of Ireland Galway, Galway, Ireland.; Physiology, School of Medicine, National University of Ireland Galway, Galway, Ireland., Finn DP; Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, Galway, Ireland.; Physiology, School of Medicine, National University of Ireland Galway, Galway, Ireland.
Jazyk:	angličtina
Zdroj:	Pain [Pain] 2021 Feb 01; Vol. 162 (2), pp. 405-420.
DOI:	10.1097/j.pain.0000000000002039
Abstrakt:	Abstract: Chronic pain is often comorbid with anxiety and depression, altering the level of perceived pain, which negatively affects therapeutic outcomes. The role of the endogenous mu-opioid receptor (MOP) system in pain-negative affect interactions and the influence of genetic background thereon are poorly understood. The inbred Wistar-Kyoto (WKY) rat, which mimics aspects of anxiety and depression, displays increased sensitivity (hyperalgesia) to noxious stimuli, compared with Sprague-Dawley (SD) rats. Here, we report that WKY rats are hyporesponsive to the antinociceptive effects of systemically administered MOP agonist morphine in the hot plate and formalin tests, compared with SD counterparts. Equivalent plasma morphine levels in the 2 rat strains suggested that these differences in morphine sensitivity were unlikely to be due to strain-related differences in morphine pharmacokinetics. Although MOP expression in the ventrolateral periaqueductal gray (vlPAG) did not differ between WKY and SD rats, the vlPAG was identified as a key locus for the hyporesponsivity to MOP agonism in WKY rats in the formalin test. Moreover, morphine-induced effects on c-Fos (a marker of neuronal activity) in regions downstream of the vlPAG, namely, the rostral ventromedial medulla and lumbar spinal dorsal horn, were blunted in the WKY rats. Together, these findings suggest that a deficit in the MOP-induced recruitment of the descending inhibitory pain pathway may underlie hyperalgesia to noxious inflammatory pain in the WKY rat strain genetically predisposed to negative affect. (Copyright © 2020 International Association for the Study of Pain.)
Databáze:	MEDLINE
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