The Antinociceptive Properties of the Corydalis yanhusuo Extract.
Corydalis yanhusuo. W.T. extracts (YHS) are widely used for the treatment of pain and inflammation. There are a few studies that assessed the effects of YHS in pain assays; however, none of these studies has systematically compared its activities in the different pain animal modes namely: acute, inflammatory and chronic pain. Furthermore, little is known about the mechanism of YHS activity in these assays. The aim of this study was to systematically evaluate the antinociceptive properties of YHS by testing it in four standardized pain assays and to investigate its mechanism. YHS antinociceptive properties were analyzed in the tail flick, the formalin paw licking, the von Frey filament and the hot box assays after spinal nerve ligation, which monitors acute nociceptive, persistent inflammatory and chronic neuropathic pain, respectively. YHS pharmacological profile was determined by screening it against a battery of G-protein coupled receptors and its mechanism of action was studied using knock-out mice. Our study shows that YHS, at a non-sedative dose, increases the tail flick latency in the tail flick assay without resulting in development of tolerance. YHS also decreases paw licking time in the formalin assay. Further, YHS increases paw withdraw threshold and latency in the von Frey filament and the hot box assays, respectively. In vitro, YHS exhibits prominent dopamine receptor antagonistic properties. In dopamine D2 receptor knockout mice, its antinociceptive effects are attenuated in acute and neuropathic pain but not inflammatory pain assays. Our results therefore indicate that YHS effectively attenuates acute, inflammatory and neuropathic pain, without causing tolerance. The effects on acute and neuropathic pain, but not inflammatory pain, are at least partially mediated through dopamine D2 receptor antagonism. Since YHS is a dietary supplement commercially available in the United States, our data suggest that it might be a candidate for alternative pain treatment.
Department of Pharmacology, University of California Irvine, Irvine, California, United States of America.
Lien
L
Wang
Department of Pharmacology, University of California Irvine, Irvine, California, United States of America.
Yan
Y
Zhang
Department of Pharmacology, University of California Irvine, Irvine, California, United States of America.
Zhiwei
Z
Wang
Department of Anesthesiology and Perioperative Care, University of California Irvine, Irvine, California, United States of America.
Nian
N
Gong
Department of Anesthesiology and Perioperative Care, University of California Irvine, Irvine, California, United States of America.
Tae Dong
TD
Kweon
Department of Anesthesiology and Perioperative Care, University of California Irvine, Irvine, California, United States of America.
Benjamin
B
Vo
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, China.
Chaoran
C
Wang
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, China.
Xiuli
X
Zhang
Department of Pharmacology, University of California Irvine, Irvine, California, United States of America.
Jae Yoon
JY
Chung
Department of Pharmacology, University of California Irvine, Irvine, California, United States of America.
Amal
A
Alachkar
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, China.
Xinmiao
X
Liang
Department of Anesthesiology and Perioperative Care, University of California Irvine, Irvine, California, United States of America.
David Z
DZ
Luo
Department of Pharmacology, University of California Irvine, Irvine, California, United States of America.|Department of Pharmaceutical Sciences, University of California Irvine, Irvine, California, United States of America.|Developmental and Cell Biology, University of California Irvine, Irvine, California, United States of America.
Olivier
O
Civelli
D059787:Acute Pain / Q000188:drug therapy; D000700:Analgesics / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D031311:Corydalis; D004361:Drug Tolerance; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D009437:Neuralgia / Q000188:drug therapy; D010147:Pain Measurement / Q000379:methods; D017448:Receptors, Dopamine D2 / Q000172:deficiency / Q000235:genetics
D000700:Analgesics; C000600618:DRD2 protein, mouse; D004365:Drugs, Chinese Herbal; D017448:Receptors, Dopamine D2