Tephrosia toxicaria Pers. reduces temporomandibular joint inflammatory hypernociception: the involvement of the HO-1 pathway

Eur J Pain. 2014 Oct;18(9):1280-9. doi: 10.1002/j.1532-2149.2014.488.x. Epub 2014 Apr 9.

Abstract

Background: We investigated both the efficacy and the sub-chronic toxicity of Tephrosia toxicaria Pers. in the zymosan-induced temporomandibular joint (TMJ) inflammatory hypernociception in rats evaluating the possible role of heme oxygenase-1 (HO-1).

Methods: Rats were pretreated with T. toxicaria (0.2, 2.0 or 20 mg/kg) 60 min before the intra-articular injection of zymosan (2 mg, 40 μL) in the left TMJ. In another series of experiments, rats were treated with ZnPP-IX (3 mg/kg), a specific HO-1 inhibitor, before T. toxicaria (20 mg/kg). Von Frey test was used to evaluate inflammatory hypernociception (g) 4 h after zymosan injection. Six hours after zymosan injection, the synovial lavage was collected for total cell count and myeloperoxidase (MPO) activity, and joint tissue for histopathological analysis and immunohistochemistry for HO-1. To evaluate the sub-chronic toxicity, mice received T. toxicaria (20 mg/kg) or saline once a day for 14 days to analyse body mass, organ weight and biochemical parameters.

Results: T. toxicaria partially reversed the zymosan-induced head withdrawal threshold, the number of cells and the MPO activity. T. toxicaria reduced the inflammatory cell influx in the synovial membrane. TMJ immunohistochemical analyses treated with T. toxicaria showed increased HO-1 expression. These effects of T. toxicaria were not observed in the presence of ZnPP-IX. T. toxicaria treatment for 14 days did not show significant signs of toxicity when administrated to mice.

Conclusions: T. toxicaria did not produce any signs of toxicity and effectively decreased zymosan-induced TMJ inflammatory hypernociception dependent, at least in part, upon the HO-1 pathway integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology
  • Heme Oxygenase-1 / antagonists & inhibitors
  • Heme Oxygenase-1 / metabolism*
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy*
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Male
  • Metabolic Networks and Pathways
  • Mice
  • Phytotherapy*
  • Plant Preparations / administration & dosage
  • Plant Preparations / adverse effects
  • Plant Preparations / pharmacology*
  • Protoporphyrins / administration & dosage
  • Protoporphyrins / pharmacology
  • Rats
  • Rats, Wistar
  • Temporomandibular Joint Disorders / chemically induced
  • Temporomandibular Joint Disorders / drug therapy*
  • Temporomandibular Joint Disorders / physiopathology
  • Tephrosia*
  • Zymosan / pharmacology

Substances

  • Enzyme Inhibitors
  • Plant Preparations
  • Protoporphyrins
  • zinc protoporphyrin
  • Zymosan
  • Heme Oxygenase-1