Pra-C exerts analgesic effect through inhibiting microglial activation in anterior cingulate cortex in complete Freund's adjuvant-induced mouse model

Mol Pain. 2021 Jan-Dec:17:1744806921990934. doi: 10.1177/1744806921990934.

Abstract

Chronic pain is highly prevalent worldwide and severely affects daily lives of patients and family members. Praeruptorin C (Pra-C) is a main active ingredient derived from Peucedanum praeruptorum Dunn, traditionally used as antibechic, anti-bronchitis and anti-hypertension drug. Here, we evaluated the effects of Pra-C in a chronic inflammatory pain mouse model induced by complete Freund's adjuvant (CFA) injection. Pra-C (3 mg/kg) treatment for just 3 days after CFA challenge relieved CFA-induced mechanical allodynia and hindpaw edema in mice. In the anterior cingulate cortex (ACC), Pra-C treatment inhibited microglia activation and reduced levels of proinflammatory cytokines, TNF-α and IL-1β, and suppressed upregulation of glutamate receptors caused by CFA injection. In addition, Pra-C attenuated neuronal hyperexcitability in ACC of CFA-injected mice. In vitro studies confirmed the analgesic effect of Pra-C was due to its inhibitory ability on microglial activation. In conclusion, Pra-C administration had a certain effect on relieving chronic pain by inhibiting microglial activation, attenuating proinflammatory cytokine releasing and regulating excitatory synaptic proteins in the ACC of the CFA-injected mice.

Keywords: Praeruptorin C; inflammatory pain; microglia; proinflammatory cytokine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology*
  • Analgesics / therapeutic use
  • Animals
  • Cell Line
  • Chronic Pain / complications
  • Chronic Pain / drug therapy
  • Chronic Pain / physiopathology
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • Coumarins / therapeutic use
  • Cytokines / metabolism
  • Disease Models, Animal
  • Edema / complications
  • Edema / pathology
  • Edema / physiopathology
  • Freund's Adjuvant
  • Gyrus Cinguli / pathology*
  • Hyperalgesia / complications
  • Hyperalgesia / pathology
  • Hyperalgesia / physiopathology
  • Inflammation / complications
  • Inflammation / drug therapy
  • Inflammation Mediators / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / pathology*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Synapses / drug effects
  • Synapses / metabolism
  • Synaptic Transmission / drug effects
  • Up-Regulation / drug effects

Substances

  • Analgesics
  • Coumarins
  • Cytokines
  • Inflammation Mediators
  • praeruptorin C
  • Freund's Adjuvant