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Lumbosacral spinal proteomic changes during PAR4-induced persistent bladder pain.

Shaojing Ye1, Nilesh M Agalave2, Fei Ma1

  • 1Lexington VA Health Care System, Research and Development, Lexington, KY, USA.

Neuroscience Letters
|November 30, 2023
PubMed
Summary
This summary is machine-generated.

Repeated activation of protease-activated receptor-4 (PAR4) causes persistent bladder pain in mice. This study found significant spinal proteomic changes, including altered proteins related to neuroprotection and mitochondria, offering potential therapeutic targets for bladder pain.

Keywords:
MetallothioneinsPersistent bladder painSpinal proteins

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Area of Science:

  • Neuroscience
  • Proteomics
  • Pain Research

Background:

  • Protease-activated receptor-4 (PAR4) activation is linked to persistent bladder hyperalgesia (BHA).
  • Understanding the central mechanisms, specifically spinal changes, is crucial for developing effective pain management strategies.

Purpose of the Study:

  • To investigate the spinal proteomic alterations associated with persistent BHA induced by PAR4 activation.
  • To identify potential novel therapeutic targets within the spinal cord for modulating chronic bladder pain.

Main Methods:

  • Persistent BHA was induced in female mice via repeated intravesical instillation of PAR4-activating peptide (PAR4-AP).
  • Spinal proteomic analysis was performed on L6-S1 segments using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with tandem-mass tag (TMT) quantification.
  • Changes in specific protein levels, such as metallothionein 1/2, were validated using immunohistochemistry.

Main Results:

  • LC-MS/MS analysis identified and quantified 6739 proteins in the spinal cord.
  • A total of 80 proteins showed significant changes in the persistent BHA group, with 29 decreasing and 51 increasing.
  • These altered proteins were associated with critical biological processes including neuroprotection, redox modulation, mitochondrial function, and neuronal activity.

Conclusions:

  • Persistent BHA induced by PAR4 activation is associated with significant changes in spinal protein expression.
  • Identified proteins represent potential novel therapeutic targets for managing persistent bladder pain at the spinal level.
  • Future research will explore the role of spinal MIF antagonism in modulating these PAR4-induced spinal proteomic changes.