Related Experiment Video
Updated: Nov 8, 2025

Cheek Injection Model for Simultaneous Measurement of Pain and Itch-related Behaviors
Published on: September 27, 2019
Bilirubin Induces Pain Desensitization in Cholestasis by Activating 5-Hydroxytryptamine 3A Receptor in Spinal Cord
Erliang Kong1,2, Hongqian Wang1,3, Xiaoqiang Wang4
1Department of Anesthesiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
Background:
Cholestasis patients often suffer from pain desensitization, resulting in serious complications in perioperative period. This study was aim to investigate the mechanism of bilirubin in cholestasis mediating pain desensitization through 5-hydroxytryptamine 3A (5-HT3 ) receptor activation in spinal dorsal horn (SDH).
Methods:
A cholestasis model was established by bile duct ligation (BDL) in rats. Pain thresholds of rats were measured after BDL or intrathecally injecting bilirubin in the presence or absence of agonist (mCPBG) and antagonists (ondansetron, bicuculline, or CGP55845). Expression of 5-HT3 receptors, and the affinity and binding mode of bilirubin to 5-HT3 receptor were determined. Effects of bilirubin on γ-aminobutyric acid (GABA) pathway and the interactions with 5-HT3 receptor were tested.
Results:
Bilirubin was elevated significantly in both serum and CSF in BDL rats, accompanied with the up-regulation of pain thresholds. Both of 5-HT3 receptor and GABA receptor antagonists could reverse the increased pain threshold in BDL rats. Further, 5-HT3 and GABA receptor expressions were increased in BDL rats or intervention with bilirubin. Molecular docking suggested that bilirubin entered the hydrophobic pocket pre-formed in 5-HT3 receptor with potential hydrogen bonding. Bilirubin also increased GABA concentrations in CSF and GABAergic spontaneous inhibitory postsynaptic current in spinal cord, and directly induced inward currents in HEK293 cells which were overexpressed 5-HT3 receptor by lentivirus.
Conclusion:
In conclusion, bilirubin induced pain desensitization in cholestasis by activating 5-HT3 receptor in spinal cord. The activation of 5-HT3 receptor might regulate pain threshold by acting on the GABA pathway.
Related Concept Videos
Analgesia and Pain Management
Pain
Nociception
Opioid Receptors: Overview
Chronic Pancreatitis I: Introduction
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...

