Abstract
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.
Highlights
Pain is an unpleasant sensory and emotional experience associated with tissue damage [1]
We show that yanhusuo. W.T. extracts (YHS) at 500 mg/kg displays a significant antinociceptive effect (P < 0.001, Fig 1B), while a mixture of l-THP and DHCB at 1 mg/kg had no effect (P > 0.05, Fig 1B), possibly indicating that other components in YHS are necessary for full antinociceptive activity
Pain can be classified into different types: nociceptive pain activated by noxious physical stimulus, inflammatory pain activated by the immune system upon tissue injury and neuropathic pain caused by damage to the nervous system resulting from physical damage or disease affecting the somatosensory system [1]
Summary
Pain is an unpleasant sensory and emotional experience associated with tissue damage [1]. Pain management is currently limited, for chronic pain. The potent opiate drugs are common and effective against some types of moderate to severe pain [2]. This class of drug, causes severe side effects [3, 4]. Anticonvulsants, antidepressants and selective serotonin noradrenaline reuptake inhibitors are used, but not exclusively, for neuropathic pain treatment with limited effectiveness [5]. New analgesic alternatives are still being explored and pursued with every effort
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