Sanguinarine Attenuates Neuropathic Pain by Inhibiting P38 MAPK Activated Neuroinflammation in Rat Model

Drug Des Devel Ther. 2020 Nov 4:14:4725-4733. doi: 10.2147/DDDT.S276424. eCollection 2020.

Abstract

Background: Neuropathic pain seriously affects life quality, and it is urgent to develop novel drugs with high efficacy and few side effects. Sanguinarine (SG) is a natural plant medicine with anti-inflammatory and neuroprotection effects. This study aimed to investigate the effect of SG on chronic constriction injury (CCI)-induced neuropathic pain.

Materials and methods: CCI rat model was established and rats were randomly divided into sham group, sham + SG group (6.25 mg/kg), CCI group, CCI + SG group (1.00, 2.50 and 6.25 mg/kg). The mechanical sensitivity and heat hypersensitivity of rats were monitored at different time points. Immunohistochemical, PCR, Western blot and ELISA were used to analyze p-p38 MAPK, NF-κB p65, TNF-α, IL-1β, and IL-6 levels.

Results: The mechanical sensitivity and heat hypersensitivity significantly reduced in rats of CCI group, but significantly increased in rats of CCI+SG group. TNF-α, IL-1β, and IL-6 levels significantly increased in the spinal cord of CCI rats, but significantly decreased in rats of CCI+SG group. In addition, p38 MAPK activator antagonized beneficial effects of SG on neuropathic pain. Overexpression of p38 MAPK reduced the mechanical sensitivity and heat hypersensitivity, and enhanced NF-κB activity and the expression of inflammatory factors in CCI rats.

Conclusion: SG alleviates neuropathic pain via suppressing p38MAPK signaling and downregulating the expression of TNF-α, IL-1β, IL-6 and NF-κB activation. SG may be a potential therapeutic agent to treat neuropathic pain.

Keywords: NF-kB; inflammatory cytokines; neuropathic pain; p38MAPK; sanguinarine.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Benzophenanthridines / pharmacology*
  • Constriction
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Isoquinolines / pharmacology*
  • Male
  • Molecular Structure
  • Neuralgia / drug therapy*
  • Neuralgia / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / metabolism
  • Structure-Activity Relationship
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Inflammatory Agents
  • Benzophenanthridines
  • Isoquinolines
  • sanguinarine
  • p38 Mitogen-Activated Protein Kinases

Grants and funding

This work was supported by the Natural Foundation of Shandong Province (no. ZR2017PH010) and Taian Science and Technology Guidance Project (no. 2017NS0143).