Document Type

Article

Presentation Date

7-24-2024

Comments

This article is the author's final published version in Neurobiology of Pain, Volume 16 , July–December 2024, Article number 100160.

The published version is available at https://doi.org/10.1016/j.ynpai.2024.100160. Copyright © 2024 The Authors. Published by Elsevier Inc.

Abstract

Recent evidence suggests that the descending modulatory pathways from the brainstem rostral ventromedial medulla (RVM) are important for bladder inflammatory pain. This study aimed to identify the long-term molecular changes in RVM neurons due to early life cystitis during neuronal development and the effect of reexposure later in adulthood. RVM tissues from two treatment protocols were used: (1) neonatal zymosan exposures with acute adult rechallenge (RC) and (2) only neonatal zymosan exposures (NRC). RNAseq analysis showed upregulation of several genes associated with synaptic plasticity (Grin1, Grip2, Notch1, Arc, and Scn2b) in the cystitis groups compared to controls in both protocols. The RC protocol exhibited a stronger treatment effect with significantly higher fold differences between the groups compared to the NRC protocol (p < 0.001, fold differences RC vs NRC). In microarrays, miR-34a-5p showed cystitis-induced downregulation in both protocols. Bioinformatics analysis identified multiple 3′UTRs complementary binding sites for miR-34a-5p on Grin2b, Notch1, Grip2, Scn2b, and Arc genes. The enhanced response in the RC protocol indicates a possible priming effect of early life cystitis on rechallenge in adulthood. These long-term molecular alterations may play a critical role in the development of chronic bladder pain conditions as seen in patients with Interstitial Cystitis/Bladder pain syndrome.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

ScienceDirect_files_04Sep2024_15-46-28.441.zip (6913 kB)
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Language

English

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