Analgesic effect of paeoniflorin in rats with neonatal maternal separation-induced visceral hyperalgesia is mediated through adenosine A1 receptor by inhibiting the extracellular signal-regulated protein kinase (ERK) pathway

Xiao Jun Zhang, Hong Li Chen, Zhi Li, Hong Qi ZHANG, Hong Xi Xu, Joseph J.Y. Sung, Zhaoxiang BIAN*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

Abstract

Paeoniflorin (PF), a chief active ingredient in the root of Paeonia lactiflora Pall (family Ranunculaceae), is effective in relieving colorectal distention (CRD)-induced visceral pain in rats with visceral hyperalgesia induced by neonatal maternal separation (NMS). This study aimed at exploring the underlying mechanisms of PF's analgesic effect on CRD-evoked nociceptive signaling in the central nervous system (CNS) and investigating whether the adenosine A1 receptor is involved in PF's anti-nociception. Results: CRD-induced visceral pain as well as phosphorylated-extracellular signal-regulated protein kinase (p-ERK) and phospho-cAMP response element-binding protein (p-CREB) expression in the CNS structures of NMS rats were suppressed by NMDA receptor antagonist dizocilpine (MK-801) and ERK phosphorylation inhibitor U0126. PF could similarly inhibit CRD-evoked p-ERK and c-Fos expression in laminae I-II of the lumbosacral dorsal horn and anterior cingulate cortex (ACC). PF could also reverse the CRD-evoked increased glutamate concentration by CRD as shown by dynamic microdialysis monitoring in ACC, whereas, DPCPX, an antagonist of adenosine A1 receptor, significantly blocked the analgesic effect of PF and PF's inhibition on CRD-induced p-ERK and p-CREB expression. These results suggest that PF's analgesic effect is possibly mediated by adenosine A1 receptor by inhibiting CRD-evoked glutamate release and the NMDA receptor dependent ERK signaling.

Original languageEnglish
Pages (from-to)88-97
Number of pages10
JournalPharmacology Biochemistry and Behavior
Volume94
Issue number1
DOIs
Publication statusPublished - Nov 2009

Scopus Subject Areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

User-Defined Keywords

  • Adenosine A receptor
  • Analgesia
  • Extracellular signal-regulated protein kinase (ERK)
  • Neonatal maternal separation
  • Paeoniflorin

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