Bulleyaconitine A Inhibits Visceral Nociception and Spinal Synaptic Plasticity through Stimulation of Microglial Release of Dynorphin A. (23rd May 2020)

• Record Type: Journal Article
• Authors: Huang, Sheng-Nan; Wei, Jinbao; Huang, Lan-Ting; Ju, Pei-Jun; Chen, Jinghong; Wang, Yong-Xiang
• Other Names: Yi Ming Guest Editor.
• Is Part Of: Neural plasticity. Volume 2020(2020)
• Publication Date: 2020-05-23
• Subjects: Neuroplasticity -- Periodicals; 612.82
• DOI: 10.1155/2020/1484087
• Languages: English
• ISSNs: 2090-5904

Abstract

Abstract : Background . Visceral pain is one of the most common types of pain and particularly in the abdomen is associated with gastrointestinal diseases. Bulleyaconitine A (BAA), isolated from Aconitum bulleyanum, is prescribed in China to treat chronic pain. The present study is aimed at evaluating the mechanisms underlying BAA visceral antinociception. Methods . The rat model of chronic visceral hypersensitivity was set up by colonic perfusion of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) on postnatal day 10 with coapplication of heterotypic intermittent chronic stress (HeICS). Results . The rat model of chronic visceral hypersensitivity exhibited remarkable abdominal withdrawal responses and mechanical hyperalgesia in hind paws, which were dose-dependently attenuated by single subcutaneous of administration of BAA (30 and 90 μ g/kg). Pretreatment with the microglial inhibitor minocycline, dynorphin A antiserum, and κ -opioid receptor antagonist totally blocked BAA-induced visceral antinociception and mechanical antihyperalgesia. Spontaneous excitatory postsynaptic currents (sEPSCs) in spinal dorsal horn lamina II neurons were recorded by using whole-cell patch clamp. Its frequency (but not amplitude) from TNBS-treated rats was remarkably higher than that from naïve rats. BAA (1 μ M) significantly reduced the frequency of sEPSCs from TNBS-treated rats but not naïve rats. BAA-inhibited spinal synaptic plasticity was blocked by minocycline, the dynorphin A antiserum, and κ -opioid receptor antagonist. Dynorphin A also inhibited spinal synaptic plasticity in a κ -opioid receptor-dependent manner. Conclusions . These results suggest that BAA produces visceral antinociception by stimulating spinal microglial release of dynorphin A, which activates presynaptic κ -opioid receptors in afferent neurons and inhibits spinal synaptic plasticity, highlighting a novel interaction mode between microglia and neurons.