Related Experiment Video

Updated: Nov 5, 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

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NADPH-Oxidase 2 Promotes Autophagy in Spinal Neurons During the Development of Morphine Tolerance

Xuyang Xiao1, Huilian Bu2, Zhisong Li1

  • 1Department of Anesthesiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Neurochemical Research
|May 19, 2021
PubMed

Insights

Chronic morphine use causes tolerance by increasing NADPH-oxidase 2 (NOX2) in the spinal cord, which activates autophagy and leads to pain relief reduction. NOX2 inhibition may treat morphine tolerance.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Cell Biology

Background:

  • Repeated morphine administration leads to analgesic tolerance, a significant clinical challenge.
  • The precise molecular mechanisms driving morphine tolerance are not fully understood.
  • NADPH-oxidase 2 (NOX2), a producer of reactive oxygen species, has an uninvestigated role in morphine tolerance.

Purpose of the Study:

  • To investigate the role of NADPH-oxidase 2 (NOX2) in the development of morphine analgesic tolerance.
  • To explore the relationship between NOX2, autophagy, and spinal cord changes during morphine tolerance.

Main Methods:

  • Chronic morphine administration in rats.
  • Measurement of NOX2 expression in the spinal cord.
  • Administration of a NOX2 inhibitor.
  • Assessment of autophagy markers (LC3B, P62) and neuronal localization (NeuN).

Main Results:

  • Chronic morphine significantly increased spinal cord NOX2 expression.
  • NOX2 inhibition prevented NOX2 upregulation and suppressed autophagy markers (LC3B, P62).
  • NOX2 inhibition blocked the development of morphine tolerance.
  • NOX2 and LC3B were found in spinal dorsal horn neurons (NeuN-positive) in tolerant rats.

Conclusions:

  • Increased spinal neuronal autophagy activity, driven by NOX2 activation, contributes to morphine analgesic tolerance.
  • NOX2 plays a critical role in the development of morphine tolerance.
  • NOX2 represents a potential therapeutic target for managing morphine tolerance.
Keywords:
AutophagyMorphine toleranceNADPH oxidaseReactive oxygen species

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