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CC BY 4.0 · J Neurol Surg Rep 2025; 86(02): e99-e106
DOI: 10.1055/a-2561-8065
Original Report

The Mechanism of HDAC2 Inhibitors on Chronic Pancreatitis Pain

Xiang-tian Zeng   *
1   Central Supply Service Department, Ganzhou People's Hospital, Ganzhou, Jiangxi, People's Republic of China
,
Wen-hui Chen   *
2   Department of Hepatopancreatobiliary Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, People's Republic of China
,
Ding-wen Zhong
2   Department of Hepatopancreatobiliary Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, People's Republic of China
,
Qi-xin Dai
2   Department of Hepatopancreatobiliary Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, People's Republic of China
,
Yong He
2   Department of Hepatopancreatobiliary Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, People's Republic of China
,
Rong-Qiang Ye
2   Department of Hepatopancreatobiliary Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, People's Republic of China
,
Xiu-lin Xiao
2   Department of Hepatopancreatobiliary Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, People's Republic of China
,
Yong-hui Liao 
2   Department of Hepatopancreatobiliary Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, People's Republic of China
› Author Affiliations Funding The study was supported by the Natural Science Foundation of Jiangxi Province (No. 20212BAB206083) and the Joint Science Foundation of Science and Technology Bureau of Ganzhou City (2022-YB1415). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.
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Abstract

Background

Chronic pancreatitis (CP) is marked by persistent inflammation and fibrosis of the pancreas, often causing severe abdominal pain. The pain mechanism involves complex interactions between pancreatic inflammation and spinal nerve activity. Histone deacetylase 2 (HDAC2) is implicated in neural processes and pain modulation, making it a potential target for CP pain management.

Aim

This study investigates HDAC2's role in CP pain and evaluates the effects of its inhibition in a CP rat model.

Methods

CP was induced in male Sprague–Dawley rats using dibutyltin dichloride (DBTC). HDAC2 expression in spinal and pancreatic tissues was assessed through western blotting, quantitative Real-Time PCR, and enzyme-linked immunosorbent assay (ELISA). Pain sensitivity was evaluated using paw withdrawal tests. Co-cultures of AR42J pancreatic acinar cells and F11 spinal neurons were used to explore pancreatic–neural interactions. Chromatin immunoprecipitation (ChIP) and promoter assays examined HDAC2 transcriptional regulation.

Results

HDAC2 expression was significantly elevated in CP rats, which also displayed increased pain sensitivity and higher inflammatory markers (interleukin [IL]-1β [IL-1β], tumor necrosis factor-α [TNF-α], IL-6, and chemokine ligand 2 [CCL-2]). HDAC2 inhibition reduced pain sensitivity and pancreatitis. Co-culture experiments revealed that pancreatic inflammatory mediators upregulate HDAC2 in neurons. ChIP identified Sp1 as a regulatory factor for HDAC2, with the extracellular signal-regulated kinase-Specific protein 1 (ERK-Sp1) pathway critical for its expression.

Conclusion

HDAC2 is crucial in CP pain sensitization and inflammation. Its inhibition reduces pain and inflammation, offering potential for targeted pain management in CP.

Keywords

chronic pancreatitis - spinal nerve - HDAC2 - ERK-Sp1 pathway - pain

Authors' Contributions

X-t.Z. and D-w.Z. contributed to writing the original draft, methodology, and supervision, while D-w.Z. also handled data curation and methodology. W-h.C. was responsible for investigation, formal analysis, and validation. Y.H. and Q-x.D. conducted formal analysis and visualization, whereas R-q.Y. and X-l.X. focused on methodology and software. Y-h.L. oversaw conceptualization, project administration, resources, and writing—review and editing. All authors read and approved the final version of the manuscript.


Ethical Approval

All aspects of this animal study were approved by the Animal Use and Care Committee for Research and Education of Ganzhou People's Hospital.


Availability of Data and Materials

All data generated or analyzed during this study are included in this published article.


* These authors contributed equally to this work and should be considered co-first authors.




Publication History

Received: 26 September 2024

Accepted: 08 March 2025

Article published online:
07 May 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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