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Updated: Jan 5, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Effect of ethanol extracts of Hericium erinaceus mycelium on morphine‑induced microglial migration
Chung-Hsin Yeh1, Li-Wei Sun2, Chang-Mei Lai3
1College of Nursing and Health Sciences, Da‑Yeh University, Changhua 51591, Taiwan, R.O.C.
Abstract:
Microglia serve important roles in chronic pain signal transduction pathways. Glia cells, especially microglia, seem to share mechanisms that lead to chronic pain and morphine‑induced tolerance. Evidence has suggested that downregulating cytoskeleton activity in microglia provides pain relief in chronic pain and morphine tolerance. The purpose of the present study was to evaluate the effect of ethanol extracts of Hericium erinaceus (EHE) mycelium on morphine‑induced BV2 microglial cell activation. BV2 cells were starved for 4 h in DMEM before being incubated with 100 ng/ml EHE for 30 min, followed by 1 µM morphine for 2 h. Subsequently, the cells were harvested and used for migration experiments and western blotting. The results showed that 1 µM morphine enhanced BV2 cell activation and chemotactic reaction, and it increased histone deacetylase 6 (HDAC6) expression and heat shock protein 90 (HSP90) deacetylation as well as HSP90 cleavage. Pretreatment with 100 ng/ml EHE significantly inhibited the morphine‑stimulated effects on BV2 cells. The present study demonstrated that EHE inhibited morphine‑induced BV2 activations by regulating the HDAC6/HSP90 deacetylation signal transduction pathway.
Insights
Ethanol extracts of Hericium erinaceus (EHE) mycelium reduced morphine-induced microglial activation. EHE targets the HDAC6/HSP90 pathway, offering potential for chronic pain and morphine tolerance management.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Microglia play a key role in chronic pain and morphine tolerance.
- Downregulating microglial cytoskeleton activity may alleviate chronic pain and morphine tolerance.
Purpose of the Study:
- To investigate the effect of Hericium erinaceus (EHE) mycelium ethanol extract on morphine-induced activation of BV2 microglial cells.
Main Methods:
- BV2 cells were treated with EHE followed by morphine.
- Cell activation and chemotaxis were assessed.
- Western blotting was used to analyze histone deacetylase 6 (HDAC6) and heat shock protein 90 (HSP90) signaling.
Main Results:
- Morphine increased BV2 cell activation, chemotaxis, HDAC6 expression, and HSP90 deacetylation/cleavage.
- EHE pretreatment significantly inhibited these morphine-induced effects.
Conclusions:
- EHE inhibits morphine-induced microglial activation by modulating the HDAC6/HSP90 deacetylation pathway.
- This suggests EHE's potential therapeutic value for chronic pain and morphine tolerance.

