Levo-Tetrahydropalmatine Attenuates Bone Cancer Pain by Inhibiting Microglial Cells Activation

Mediators Inflamm. 2015:2015:752512. doi: 10.1155/2015/752512. Epub 2015 Dec 27.

Abstract

Objective: The present study is to investigate the analgesic roles of L-THP in rats with bone cancer pain caused by tumor cell implantation (TCI).

Methods: Thermal hyperalgesia and mechanical allodynia were measured at different time points before and after operation. L-THP (20, 40, and 60 mg/kg) were administrated intragastrically at early phase of postoperation (before pain appearance) and later phase of postoperation (after pain appearance), respectively. The concentrations of TNF-α, IL-1β, and IL-18 in spinal cord were measured by enzyme-linked immunosorbent assay. Western blot was used to test the activation of astrocytes and microglial cells in spinal cord after TCI treatment.

Results: TCI treatment induced significant thermal hyperalgesia and mechanical allodynia. Administration of L-THP at high doses significantly prevented and/or reversed bone cancer-related pain behaviors. Besides, TCI-induced activation of microglial cells and the increased levels of TNF-α and IL-18 were inhibited by L-THP administration. However, L-THP failed to affect TCI-induced astrocytes activation and IL-1β increase.

Conclusion: This study suggests the possible clinical utility of L-THP in the treatment of bone cancer pain. The analgesic effects of L-THP on bone cancer pain maybe underlying the inhibition of microglial cells activation and proinflammatory cytokines increase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Berberine Alkaloids / pharmacology*
  • Bone Neoplasms / physiopathology*
  • Dose-Response Relationship, Drug
  • Female
  • Hyperalgesia / drug therapy
  • Interleukin-18 / analysis
  • Microglia / drug effects*
  • Microglia / physiology
  • Neoplasm Transplantation
  • Pain, Intractable / drug therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • Berberine Alkaloids
  • Interleukin-18
  • Tumor Necrosis Factor-alpha
  • tetrahydropalmatine