Related Experiment Video

Updated: May 15, 2025

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

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Contributions of synaptic energetic dysfunction by microtubule dynamics and microtubule-based mitochondrial transport

Zheng Li1,2, Jie Liu1, Jie Ju1

  • 1Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

British Journal of Pharmacology
|May 14, 2025
PubMed
Abstract

Insights

Chronic morphine use impairs synaptic energy by disrupting microtubules. Stabilizing microtubules via the Ca2+-CAMKK2-AMPK pathway can restore synaptic ATP and potentially prolong pain relief.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pharmacology

Background:

  • Long-term morphine use leads to analgesic tolerance.
  • Synaptic adenosine triphosphate (ATP) supply is vital for neuronal function.
  • Microtubules are crucial for mitochondrial transport and energy delivery.

Purpose of the Study:

  • Investigate how morphine affects synaptic energy supply.
  • Determine the role of microtubule cytoskeleton in morphine tolerance.
  • Elucidate the mechanism of microtubule dynamics under morphine exposure.

Main Methods:

  • Morphine treatment in rats and SH-SY5Y cells.
  • Tail-flick latency test for pain threshold evaluation.
  • Pharmacological modulation of synaptic pathways and microtubule stability.

Main Results:

  • Chronic morphine reduced synaptic mitochondrial ATP production.
  • Microtubule stabilization ameliorated energy deficits and prevented disruption.
  • The Ca2+-CAMKK2-AMPK pathway regulated microtubule expression and synaptic ATP.

Conclusions:

  • The microtubule cytoskeleton, regulated by the Ca2+-CAMKK2-AMPK axis, is essential for synaptic mitochondrial transport and ATP production.
  • This highlights a link between chronic morphine-induced neuroadaptation and synaptic energy dysfunction.
  • Findings suggest potential strategies to enhance long-term opioid efficacy in pain management.
Keywords:
microtubulemitochondriamorphine tolerancesynaptic energetics

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