Involvement of NOTCH1-mediated Microglia Activation in Neuromodulation of Chronic Prostatitis-related Pain

Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved..

BACKGROUND/AIM: This study aimed to investigate the role of NOTCH receptor 1 (NOTCH1)-mediated activation of microglia in the L5-S2 spinal dorsal horn in chronic prostatitis pain.

MATERIALS AND METHODS: Rats were divided into chronic prostatitis (CP) group and control group. Complete Freund's adjuvant was injected into the prostate, and prostate pathology and pain-related behavior were monitored to assess the successful establishment of the CP-related pain model. The dorsal horn of the L5-S2 spinal cord was collected for the detection of ionized calcium-binding adapter molecule 1 (IBA-1) and NOTCH1 expression by quantitative real time polymerase chain reaction and the detection of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) by enzyme-linked immunosorbent assay. Electrical excitability was assessed with whole-cell patch clamp. In addition, NOTCH1 receptor inhibitor or inhibitor of microglial cell activation was injected into the subarachnoid space, and the pro-inflammatory cytokines in the spinal cord were detected.

RESULTS: In the CP group, the expression of NOTCH1, IBA-1, TNF-α and IL-1β began to increase at 4 days, peaked at 12 days, and began to decline at 24 days, and it was significantly higher than in the control group (p<0.01). Inhibition of microglia or NOTCH1 receptor markedly reduced the content of TNF-α and IL-1β in the spinal cord (p<0.05). At 4, 12 and 24 days, the amplitude and frequency of neuronal action potential increased and the threshold decreased markedly as compared to the control group (p<0.05), and spontaneous action potential was noted.

CONCLUSION: NOTCH1 mediates the activation of microglia in the L5-S2 spinal cord, leading to the secretion of inflammatory factors and enhanced electrical excitability of neurons, which is related to persistent and refractory chronic prostatitis-related pain.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:38

Enthalten in:

In vivo (Athens, Greece) - 38(2024), 2 vom: 27. März, Seite 691-698

Sprache:

Englisch

Beteiligte Personen:

Zhang, Heng [VerfasserIn]
Gu, Ruifen [VerfasserIn]
Luo, Jisheng [VerfasserIn]
Zhong, Chuanhua [VerfasserIn]
Pan, Jinhong [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
Microglia
NOTCH1
NOTCH1 protein, human
Neuron
Notch1 protein, rat
Prostatitis-related pain
Receptor, Notch1
Spinal cord
Tumor Necrosis Factor-alpha

Anmerkungen:

Date Completed 01.03.2024

Date Revised 04.03.2024

published: Print

Citation Status MEDLINE

doi:

10.21873/invivo.13490

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369080610