Related Experiment Video

Updated: Oct 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

Published on: July 29, 2014

33.6K

AMPK-autophagy-mediated inhibition of microRNA-30a-5p alleviates morphine tolerance via SOCS3-dependent

Li Wan1, Ru-Meng Jia1, Lu-Lu Ji1

  • 1Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.

Journal of Neuroinflammation
|January 30, 2022
PubMed
Abstract

Insights

AMPK-autophagy activation suppresses neuroinflammation and improves morphine tolerance by upregulating SOCS3 through inhibiting microRNA-30a-5p processing. This finding offers a novel therapeutic strategy for managing pain and opioid tolerance.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Morphine tolerance, a significant clinical issue in pain management, is closely linked to neuroinflammation.
  • AMPK-autophagy activation has emerged as a potential modulator of analgesic tolerance.

Purpose of the Study:

  • To investigate the role of AMPK-autophagy in suppressing neuroinflammation and enhancing morphine efficacy.
  • To elucidate the underlying molecular mechanism involving suppressor of cytokine signaling 3 (SOCS3) and microRNA-30a-5p.

Main Methods:

  • Morphine tolerance was assessed in CD-1 mice using the tail-flick test.
  • Microglial cell line BV-2 was used to study the posttranscriptional regulation of SOCS3.
  • Western blotting, real-time PCR, and immunofluorescence staining were employed to measure cytokine levels, SOCS3, and miRNA-processing enzymes.

Main Results:

  • MicroRNA-30a-5p was identified as a negative regulator of SOCS3.
  • AMPK activators (AICAR, resveratrol, metformin) downregulated microRNA-30a-5p by inhibiting its processing and maturation via autophagy-mediated degradation of DICER and AGO2.
  • Inhibition of microRNA-30a-5p significantly improved morphine tolerance, upregulated SOCS3, and reduced neuroinflammation markers (IL-1β, TNF-α) in mice and microglia.

Conclusions:

  • AMPK-autophagy activation effectively suppresses neuroinflammation and ameliorates morphine tolerance.
  • This beneficial effect is mediated by the upregulation of SOCS3 through the inhibition of microRNA-30a-5p processing and maturation.
  • Targeting the AMPK-autophagy-SOCS3-microRNA-30a-5p pathway presents a promising therapeutic avenue for managing pain and opioid tolerance.
Keywords:
AMPK-autophagyMorphine toleranceNeuroinflammationSOCS3microRNA-30a-5p

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