Analgesic effect of paeoniflorin in rats with neonatal maternal separation-induced visceral hyperalgesia is mediated through adenosine A(1) receptor by inhibiting the extracellular signal-regulated protein kinase (ERK) pathway.
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 A(1) 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 A(1) 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 A(1) receptor by inhibiting CRD-evoked glutamate release and the NMDA receptor dependent ERK signaling.
Zhang
Xiao-Jun
XJ
School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
Chen
Hong-Li
HL
Li
Zhi
Z
Zhang
Hong-Qi
HQ
Xu
Hong-Xi
HX
Sung
Joseph J Y
JJ
Bian
Zhao-Xiang
ZX
D058916:Adenosine A1 Receptor Antagonists; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005960:Glucosides / Q000008:administration & dosage / Q000494:pharmacology*; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008426:Maternal Deprivation; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D039821:Monoterpenes; D029596:Paeonia / Q000737:chemistry; D017288:Pain Threshold / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012020:Reflex, Abdominal / Q000187:drug effects; D014781:Viscera; D006027:Glycosides
D058916:Adenosine A1 Receptor Antagonists; D000700:Analgesics; D001565:Benzoates; D001952:Bridged-Ring Compounds; D017362:Cyclic AMP Response Element-Binding Protein; D048049:Extracellular Signal-Regulated MAP Kinases; D005960:Glucosides; D018698:Glutamic Acid; D020929:Mitogen-Activated Protein Kinase Kinases; D039821:Monoterpenes; D016760:Proto-Oncogene Proteins c-fos; D043682:Receptor, Adenosine A1; D016194:Receptors, N-Methyl-D-Aspartate; C015423:peoniflorin; D006027:Glycosides