Anti-Visceral Pain/Anxiety Effects Of Bulleyaconitine A

Visceral hypersensitivity(VHS),also known as visceral pain,is one of the most common pains in the clinical research and one of the main causes of abdominal pain in patients.Chronic visceral pain is a hallmark of many diseases,including functional dyspepsia,inflammatory bowel disease,irritable bowel syndrome,etc.Currently,there are few therapies that can effectively treat patients with chronic visceral pain.As a result,researchers are continuing to look for more effective ways to treat VHS,thereby further treating VHS-associated gastrointestinal diseases.Moreover,chronic visceral pain and some mental illness(such as anxiety)have high probability of complications in the clinical research.Treating psychiatric diseases associated with chronic pain more effectively is also a clinical problem to be solved.Bulleyacotinine A(BAA)is a C19-dioxin alkaloid isolated from Aconitum and it has strong analgesic activity and significant anti-inflammatory effects.Many studies showed that BAA played obvious abirritation in a variety of pain models(such as skin pain,neuropathic pain,cancer pain,etc.).However,there are no reports on the role of BAA in visceral pain and anxiety symptom.The main purpose of our research was to investigate the anti-visceral pain effect of BAA and its analgesic mechanism.We found that BAA exerted significant analgesic effects in two visceral pain model rats.The anti-visceral pain mechanism of BAA is to stimulate dynorphin A expression in microglia and then dynorphin A acted on κ opioid receptors,which reduced the increased presynaptic glutamate transmission in L4-L6 spinal dorsal horn neurons of rats with visceral pain.The results showed for the first time that BAA exerted significant anti-visceral pain effect,which expanded more analgesic spectrum of BAA and also provided new ideas for clinically treatment of visceral pain and its related gastrointestinal diseases such as IBS.Also,the results expanded more clinical use of BAA.This study also evaluated the anti-anxiety effects of BAA in rats with visceral pain-anxiety and anxiety models.We found for the first time that BAA exerted significant anti-anxiety effects.The results layed the foundation for further expansion of the clinical application of BAA and also provided a new evidence for clinically treatment of anxiety symptoms.