Understanding painful versus non-painful dental pain in female and male patients: A transcriptomic analysis of human biopsies.

Dental pain from apical periodontitis is an infection induced-orofacial pain condition that presents with diversity in pain phenotypes among patients. While 60% of patients with a full-blown disease present with the hallmark symptom of mechanical allodynia, nearly 40% of patients experience no pain....

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Main Authors: Biraj Patel, Michael A Eskander, Phoebe Fang-Mei Chang, Brett Chapa, Shivani B Ruparel, Zhao Lai, Yidong Chen, Armen Akopian, Nikita B Ruparel
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2023-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0291724
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author Biraj Patel
Michael A Eskander
Phoebe Fang-Mei Chang
Brett Chapa
Shivani B Ruparel
Zhao Lai
Yidong Chen
Armen Akopian
Nikita B Ruparel
author_facet Biraj Patel
Michael A Eskander
Phoebe Fang-Mei Chang
Brett Chapa
Shivani B Ruparel
Zhao Lai
Yidong Chen
Armen Akopian
Nikita B Ruparel
author_sort Biraj Patel
collection DOAJ
description Dental pain from apical periodontitis is an infection induced-orofacial pain condition that presents with diversity in pain phenotypes among patients. While 60% of patients with a full-blown disease present with the hallmark symptom of mechanical allodynia, nearly 40% of patients experience no pain. Furthermore, a sexual dichotomy exists, with females exhibiting lower mechanical thresholds under basal and diseased states. Finally, the prevalence of post-treatment pain refractory to commonly used analgesics ranges from 7-19% (∼2 million patients), which warrants a thorough investigation of the cellular changes occurring in different patient cohorts. We, therefore, conducted a transcriptomic assessment of periapical biopsies (peripheral diseased tissue) from patients with persistent apical periodontitis. Surgical biopsies from symptomatic male (SM), asymptomatic male (AM), symptomatic female (SF), and asymptomatic female (AF) patients were collected and processed for bulk RNA sequencing. Using strict selection criteria, our study found several unique differentially regulated genes (DEGs) between symptomatic and asymptomatic patients, as well as novel candidate genes between sexes within the same pain group. Specifically, we found the role of cells of the innate and adaptive immune system in mediating nociception in symptomatic patients and the role of genes involved in tissue homeostasis in potentially inhibiting nociception in asymptomatic patients. Furthermore, sex-related differences appear to be tightly regulated by macrophage activity, its secretome, and/or migration. Collectively, we present, for the first time, a comprehensive assessment of peripherally diseased human tissue after a microbial insult and shed important insights into the regulation of the trigeminal system in female and male patients.
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spelling doaj.art-21ed58555cee4070b8c476dc891859622023-09-28T05:31:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01189e029172410.1371/journal.pone.0291724Understanding painful versus non-painful dental pain in female and male patients: A transcriptomic analysis of human biopsies.Biraj PatelMichael A EskanderPhoebe Fang-Mei ChangBrett ChapaShivani B RuparelZhao LaiYidong ChenArmen AkopianNikita B RuparelDental pain from apical periodontitis is an infection induced-orofacial pain condition that presents with diversity in pain phenotypes among patients. While 60% of patients with a full-blown disease present with the hallmark symptom of mechanical allodynia, nearly 40% of patients experience no pain. Furthermore, a sexual dichotomy exists, with females exhibiting lower mechanical thresholds under basal and diseased states. Finally, the prevalence of post-treatment pain refractory to commonly used analgesics ranges from 7-19% (∼2 million patients), which warrants a thorough investigation of the cellular changes occurring in different patient cohorts. We, therefore, conducted a transcriptomic assessment of periapical biopsies (peripheral diseased tissue) from patients with persistent apical periodontitis. Surgical biopsies from symptomatic male (SM), asymptomatic male (AM), symptomatic female (SF), and asymptomatic female (AF) patients were collected and processed for bulk RNA sequencing. Using strict selection criteria, our study found several unique differentially regulated genes (DEGs) between symptomatic and asymptomatic patients, as well as novel candidate genes between sexes within the same pain group. Specifically, we found the role of cells of the innate and adaptive immune system in mediating nociception in symptomatic patients and the role of genes involved in tissue homeostasis in potentially inhibiting nociception in asymptomatic patients. Furthermore, sex-related differences appear to be tightly regulated by macrophage activity, its secretome, and/or migration. Collectively, we present, for the first time, a comprehensive assessment of peripherally diseased human tissue after a microbial insult and shed important insights into the regulation of the trigeminal system in female and male patients.https://doi.org/10.1371/journal.pone.0291724
spellingShingle Biraj Patel
Michael A Eskander
Phoebe Fang-Mei Chang
Brett Chapa
Shivani B Ruparel
Zhao Lai
Yidong Chen
Armen Akopian
Nikita B Ruparel
Understanding painful versus non-painful dental pain in female and male patients: A transcriptomic analysis of human biopsies.
PLoS ONE
title Understanding painful versus non-painful dental pain in female and male patients: A transcriptomic analysis of human biopsies.
title_full Understanding painful versus non-painful dental pain in female and male patients: A transcriptomic analysis of human biopsies.
title_fullStr Understanding painful versus non-painful dental pain in female and male patients: A transcriptomic analysis of human biopsies.
title_full_unstemmed Understanding painful versus non-painful dental pain in female and male patients: A transcriptomic analysis of human biopsies.
title_short Understanding painful versus non-painful dental pain in female and male patients: A transcriptomic analysis of human biopsies.
title_sort understanding painful versus non painful dental pain in female and male patients a transcriptomic analysis of human biopsies
url https://doi.org/10.1371/journal.pone.0291724
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