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Updated: Aug 30, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
07:23

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

Published on: July 29, 2014

Effects of morphine and time of day on pain and beta-endorphin

Natalie Ann Rasmussen1, Lynne A Farr

  • 1College of Nursing, University of Nebraska Medical Center, 985330 Nebraska Medical Center, Omaha, NE 68198-5330, USA. nrasmuss@unmc.edu

Biological Research for Nursing
|October 9, 2003
PubMed

Insights

Morphine disrupts the body's natural pain-inhibiting rhythms, leading to inconsistent pain relief. Dosing should be adjusted to optimize the body's own pain control alongside morphine for better results.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Chronobiology

Background:

  • Pain perception and analgesic effectiveness can vary significantly throughout the day.
  • The body possesses an endogenous inhibitory pain response with known circadian variations.
  • Morphine's analgesic effects may be influenced by its interaction with plasma beta-endorphin (BE) levels, which also exhibit temporal fluctuations.

Purpose of the Study:

  • To investigate the impact of morphine administration on the circadian rhythm of the pain-induced beta-endorphin (BE) response.
  • To determine if morphine's analgesic efficacy is time-dependent.
  • To understand how morphine affects the body's endogenous pain modulation system.

Main Methods:

  • Mice were administered morphine sulfate or saline (control) and exposed to an acute pain stimulus at 4-hour intervals.
  • Blood samples were collected at each interval to measure plasma beta-endorphin (BE) levels via radioimmunoassay.
  • Pain tolerance was assessed by measuring the duration animals tolerated the noxious stimulus.

Main Results:

  • Control mice exhibited a clear circadian rhythm in their BE response to pain, peaking at midnight and reaching a nadir at noon.
  • Mice treated with morphine displayed an arrhythmic BE response, indicating disruption of the natural rhythm.
  • While morphine-treated animals showed increased pain tolerance, the degree of analgesia varied depending on the time of day.

Conclusions:

  • Morphine administration effectively abolishes the circadian rhythm of the pain-induced BE response.
  • The analgesic effect of morphine is not uniform across the 24-hour cycle, suggesting time-dependent efficacy.
  • Optimizing morphine dosage requires considering its interaction with the body's endogenous pain control system, potentially allowing for reduced doses and maximized natural analgesia.

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