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Advanced age attenuates the antihyperalgesic effect of morphine and decreases μ-opioid receptor expression and binding in the rat midbrain Periaqueductal Gray in male and female rats

Evan F. Fullerton, Myurajan Rubaharan, Mary C. Karom, Richard I. Hanberry, Anne Z. Murphy
doi: https://doi.org/10.1101/2020.06.16.154740
Evan F. Fullerton
Neuroscience Institute, Georgia State University, Atlanta, Georgia, 30303, United States
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Myurajan Rubaharan
Neuroscience Institute, Georgia State University, Atlanta, Georgia, 30303, United States
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Mary C. Karom
Neuroscience Institute, Georgia State University, Atlanta, Georgia, 30303, United States
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Richard I. Hanberry
Neuroscience Institute, Georgia State University, Atlanta, Georgia, 30303, United States
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Anne Z. Murphy
Neuroscience Institute, Georgia State University, Atlanta, Georgia, 30303, United States
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  • For correspondence: amurphy@gsu.edu
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Abstract

The present study investigated the impact of advanced age on morphine modulation of persistent inflammatory pain in male and female rats. The impact of age, sex, and pain on μ-opioid receptor (MOR) expression and binding in the ventrolateral PAG (vlPAG) was also examined using immunohistochemistry and receptor autoradiography. Intraplantar administration of Complete Freund’s adjuvant induced comparable levels of edema and hyperalgesia in adult (2-3mos) and aged (16-18mos) male and female rats. Morphine potency was highest in adult males, with a two-fold decrease in morphine EC50 observed in aged versus adult males (10.22mg/kg versus 5.19mg/kg). Adult and aged female rats also exhibited significantly higher EC50 values (10.69 mg/kg and 9.00 mg/kg, respectively) compared to adult males. The upward shift in EC50 from adult to aged males was paralleled by a reduction in vlPAG MOR expression and binding. The observed age-related reductions in morphine potency and vlPAG MOR expression and binding have significant implications in pain management in the aged population.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Declarations of interest: None

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 17, 2020.
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Advanced age attenuates the antihyperalgesic effect of morphine and decreases μ-opioid receptor expression and binding in the rat midbrain Periaqueductal Gray in male and female rats
Evan F. Fullerton, Myurajan Rubaharan, Mary C. Karom, Richard I. Hanberry, Anne Z. Murphy
bioRxiv 2020.06.16.154740; doi: https://doi.org/10.1101/2020.06.16.154740
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Advanced age attenuates the antihyperalgesic effect of morphine and decreases μ-opioid receptor expression and binding in the rat midbrain Periaqueductal Gray in male and female rats
Evan F. Fullerton, Myurajan Rubaharan, Mary C. Karom, Richard I. Hanberry, Anne Z. Murphy
bioRxiv 2020.06.16.154740; doi: https://doi.org/10.1101/2020.06.16.154740

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