1. Bulleyaconitine A Inhibits Visceral Nociception and Spinal Synaptic Plasticity through Stimulation of Microglial Release of Dynorphin A.
- Author
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Huang SN, Wei J, Huang LT, Ju PJ, Chen J, and Wang YX
- Subjects
- Aconitine administration & dosage, Animals, Female, Microglia metabolism, Posterior Horn Cells drug effects, Posterior Horn Cells physiology, Rats, Sprague-Dawley, Synapses physiology, Synaptic Transmission drug effects, Visceral Pain metabolism, Aconitine analogs & derivatives, Analgesics administration & dosage, Dynorphins metabolism, Microglia drug effects, Neuronal Plasticity drug effects, Nociception drug effects, Synapses drug effects, Visceral Pain prevention & control
- 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., Competing Interests: The authors declare that there are no competing interests in this work., (Copyright © 2020 Sheng-Nan Huang et al.)
- Published
- 2020
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