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Related Experiment Video

Updated: Nov 11, 2025

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
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Offset analgesia and onset hyperalgesia with different stimulus ranges.

Jens Fust1, Maria Lalouni1, Viktor Vadenmark Lundqvist1

  • 1Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Pain Reports
|March 31, 2021
PubMed
Summary

Offset analgesia (OA) and onset hyperalgesia (OH) were studied in healthy individuals. OA was consistently elicited, but OH was only observed under specific conditions, suggesting different pain mechanisms for increasing and decreasing stimuli.

Keywords:
Endogenous pain modulationOffset analgesiaOnset hyperalgesiaThermal pain stimulation

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Area of Science:

  • Neuroscience
  • Pain Research
  • Sensory Perception

Background:

  • Offset analgesia (OA), a significant pain reduction following a brief increase in stimulus intensity, is well-researched.
  • Onset hyperalgesia (OH), a disproportionate pain increase after a brief decrease in stimulus intensity, has been minimally studied.

Purpose of the Study:

  • To investigate the induction of OA and OH in healthy participants.
  • To explore how varying temperature stimulus ranges influence OA and OH responses.

Main Methods:

  • Sixty-two participants underwent two identical experiments.
  • Conditions included temperature deviations of ±1°C and ±2°C from baseline, compared to a constant temperature control.

Main Results:

  • Offset analgesia was successfully elicited across different temperature deviations in both experiments.
  • Onset hyperalgesia was only observed with a 2°C decrease in temperature in one experiment.
  • A continuous relationship was found between stimulus range and hypoalgesic response; OH response varied, potentially due to sex differences.

Conclusions:

  • The asymmetrical pain responses to increasing versus decreasing temperature suggest distinct underlying neural mechanisms.
  • The observed asymmetry may be influenced by salient thermal cues acting as 'learning signals' that modulate subsequent pain perception.