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Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
Paeonol alleviates neuropathic pain by modulating microglial M1 and M2 polarization via the RhoA/p38MAPK signaling
Xin Li1, Huimei Shi1, Di Zhang1
1College of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
Background:
This study aimed to investigate the potential mechanism of paeonol in the treatment of neuropathic pain.
Methods:
Relevant mechanisms were explored through microglial pseudotime analysis and the use of specific inhibitors in cell experiments. In animal experiments, 32 SD rats were randomly divided into the sham operation group, the chronic constrictive injury (CCI) group, the ibuprofen group, and the paeonol group. We performed behavioral testing, ELISA, PCR, Western blotting, immunohistochemistry, and immunofluorescence analysis.
Results:
The pseudotime analysis of microglia found that RhoA, Rock1, and p38MAPK were highly expressed in activated microglia, and the expression patterns of these genes were consistent with the expression trends of the M1 markers CD32 and CD86. Paeonol decreased the levels of M1 markers (IL1β, iNOS, CD32, IL6) and increased the levels of M2 markers (IL10, CD206, ARG-1) in LPS-induced microglia. The expression of iNOS, IL1β, RhoA, and Rock1 was significantly increased in LPS-treated microglia, while paeonol decreased the expression of these proteins. Thermal hyperalgesia occurred after CCI surgery, and paeonol provided relief. In addition, paeonol decreased the levels of IL1β and IL8 and increased the levels of IL4 and TGF-β in the serum of CCI rats. Paeonol decreased expression levels of M1 markers and increased expression levels of M2 markers in the spinal cord. Paeonol decreased IBA-1, IL1β, RhoA, RhoA-GTP, COX2, Rock1, and p-p38MAPK levels in the spinal dorsal horn.
Conclusion:
Paeonol relieves neuropathic pain by modulating microglial M1 and M2 phenotypes through the RhoA/p38 MAPK pathway.
Insights
Paeonol effectively treats neuropathic pain by shifting microglia from an inflammatory M1 state to a healing M2 state via the RhoA/p38 MAPK pathway. This research offers new insights into paeonol
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Neuropathic pain is a debilitating condition with complex underlying mechanisms.
- Microglial activation plays a critical role in the development and maintenance of neuropathic pain.
- Paeonol, a natural compound, has shown potential therapeutic effects, but its precise mechanism in neuropathic pain remains unclear.
Purpose of the Study:
- To elucidate the mechanism by which paeonol alleviates neuropathic pain.
- To investigate the role of microglial polarization in paeonol's therapeutic effects.
- To explore the involvement of the RhoA/p38 MAPK pathway in paeonol-mediated pain relief.
Main Methods:
- Microglial pseudotime analysis and cell experiments with specific inhibitors.
- Animal model of chronic constrictive injury (CCI) in Sprague-Dawley rats.
- Behavioral testing, ELISA, PCR, Western blotting, immunohistochemistry, and immunofluorescence analysis.
Main Results:
- Paeonol modulated microglial polarization, decreasing M1 markers (e.g., IL1β, iNOS) and increasing M2 markers (e.g., IL10, CD206).
- Paeonol treatment reduced thermal hyperalgesia in CCI rats and altered serum cytokine profiles.
- Inhibition of the RhoA/p38 MAPK pathway was observed in paeonol-treated spinal cord tissues.
Conclusions:
- Paeonol exerts its analgesic effects by rebalancing microglial phenotypes from M1 to M2.
- The RhoA/p38 MAPK pathway is a key mediator of paeonol's action in neuropathic pain.
- Paeonol represents a promising therapeutic agent for neuropathic pain management.
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