Tetrahydropalmatine exerts analgesic effects by promoting apoptosis and inhibiting the activation of glial cells in rats with inflammatory pain

Mol Pain. 2021 Jan-Dec:17:17448069211042117. doi: 10.1177/17448069211042117.

Abstract

Background: Pain is an unpleasant sensory experience that usually plays a protective role. Inflammatory pain is often severe and stubborn, which has a great impact on the quality of life of patients. However, there has been no breakthrough in the treatment strategy and mechanism of inflammatory pain.

Methods: This study investigated the analgesic effect of tetrahydropalmatine (THP) in rats injected with complete Freund's adjuvant (CFA)-induced inflammatory pain. Allodynia and gait analysis of rats were used to evaluate the analgesic effect at different time points before and after operation. THP (2.5, 5, and 10 mg/kg) was administered intraperitoneally once daily for 7 days post Day 3. The expression levels of TNF-α and IL-1β in the spinal cord were measured by enzyme-linked immunosorbent assay. The activation of astrocytes and microglial cells in the spinal cord was tested by western blot before and after THP treatment. The apoptosis of glial cells was tested by flow cytometry after treatment with THP in the primary cultured glial cell model.

Results: CFA treatment induced significant allodynia and caused abnormal gait in rats. Administration of THP at 10 mg/kg significantly alleviated CFA-induced inflammatory pain behaviors. Moreover, CFA-induced activation of glial cells and the increased levels of TNF-α and IL-1β were inhibited by THP administration. In addition, THP promotes apoptosis in primary cultured glial cells. This study suggests the possible clinical utility of THP in the treatment of inflammatory pain.

Conclusion: THP plays an analgesic role by inhibiting the activation of glial cells and promoting apoptosis.

Keywords: Tetrahydropalmatine; apoptosis; glial cell; inflammatory pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Astrocytes / metabolism
  • Berberine Alkaloids / pharmacology*
  • Disease Models, Animal
  • Freund's Adjuvant / adverse effects
  • Hyperalgesia / drug therapy
  • Hyperalgesia / metabolism
  • Inflammation / drug therapy*
  • Male
  • Microglia / drug effects
  • Neuroglia / drug effects*
  • Neuroglia / metabolism
  • Pain / drug therapy*
  • Pain / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / metabolism

Substances

  • Berberine Alkaloids
  • tetrahydropalmatine
  • Freund's Adjuvant