A High Body Mass Index and the Vacuum Phenomenon Upregulate Pain-Related Molecules in Human Degenerated Intervertebral Discs

Animal studies suggest that pain-related-molecule upregulation in degenerated intervertebral discs (IVDs) potentially leads to low back pain (LBP). We hypothesized that IVD mechanical stress and axial loading contribute to discogenic LBP’s pathomechanism. This study aimed to elucidate the relationsh...

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Main Authors: Masayuki Miyagi, Kentaro Uchida, Sho Inoue, Shotaro Takano, Mitsufumi Nakawaki, Ayumu Kawakubo, Hiroyuki Sekiguchi, Toshiyuki Nakazawa, Takayuki Imura, Wataru Saito, Eiki Shirasawa, Akiyoshi Kuroda, Shinsuke Ikeda, Yuji Yokozeki, Yusuke Mimura, Tsutomu Akazawa, Masashi Takaso, Gen Inoue
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/6/2973
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author Masayuki Miyagi
Kentaro Uchida
Sho Inoue
Shotaro Takano
Mitsufumi Nakawaki
Ayumu Kawakubo
Hiroyuki Sekiguchi
Toshiyuki Nakazawa
Takayuki Imura
Wataru Saito
Eiki Shirasawa
Akiyoshi Kuroda
Shinsuke Ikeda
Yuji Yokozeki
Yusuke Mimura
Tsutomu Akazawa
Masashi Takaso
Gen Inoue
author_facet Masayuki Miyagi
Kentaro Uchida
Sho Inoue
Shotaro Takano
Mitsufumi Nakawaki
Ayumu Kawakubo
Hiroyuki Sekiguchi
Toshiyuki Nakazawa
Takayuki Imura
Wataru Saito
Eiki Shirasawa
Akiyoshi Kuroda
Shinsuke Ikeda
Yuji Yokozeki
Yusuke Mimura
Tsutomu Akazawa
Masashi Takaso
Gen Inoue
author_sort Masayuki Miyagi
collection DOAJ
description Animal studies suggest that pain-related-molecule upregulation in degenerated intervertebral discs (IVDs) potentially leads to low back pain (LBP). We hypothesized that IVD mechanical stress and axial loading contribute to discogenic LBP’s pathomechanism. This study aimed to elucidate the relationships among the clinical findings, radiographical findings, and pain-related-molecule expression in human degenerated IVDs. We harvested degenerated-IVD samples from 35 patients during spinal interbody fusion surgery. Pain-related molecules including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, calcitonin gene-related peptide (CGRP), microsomal prostaglandin E synthase-1 (mPGES1), and nerve growth factor (NGF) were determined. We also recorded preoperative clinical findings including body mass index (BMI), Oswestry Disability Index (ODI), and radiographical findings including the vacuum phenomenon (VP) and spinal instability. Furthermore, we compared pain-related-molecule expression between the VP (−) and (+) groups. BMI was significantly correlated with the ODI, CGRP, and mPGES-1 levels. In the VP (+) group, mPGES-1 levels were significantly higher than in the VP (−) group. Additionally, CGRP and mPGES-1 were significantly correlated. Axial loading and mechanical stress correlated with CGRP and mPGES-1 expression and not with inflammatory cytokine or NGF expression. Therefore, axial loading and mechanical stress upregulate CGRP and mPGES-1 in human degenerated IVDs, potentially leading to chronic discogenic LBP.
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spelling doaj.art-25c01837c94f4a5b9bec13c3ce14a3fd2023-11-24T01:30:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01236297310.3390/ijms23062973A High Body Mass Index and the Vacuum Phenomenon Upregulate Pain-Related Molecules in Human Degenerated Intervertebral DiscsMasayuki Miyagi0Kentaro Uchida1Sho Inoue2Shotaro Takano3Mitsufumi Nakawaki4Ayumu Kawakubo5Hiroyuki Sekiguchi6Toshiyuki Nakazawa7Takayuki Imura8Wataru Saito9Eiki Shirasawa10Akiyoshi Kuroda11Shinsuke Ikeda12Yuji Yokozeki13Yusuke Mimura14Tsutomu Akazawa15Masashi Takaso16Gen Inoue17Department of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City 252-0374, Kanagawa, JapanDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City 252-0374, Kanagawa, JapanDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City 252-0374, Kanagawa, JapanDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City 252-0374, Kanagawa, JapanDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City 252-0374, Kanagawa, JapanDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City 252-0374, Kanagawa, JapanShonan University of Medical Sciences Research Institute, Nishikubo 500, Chigasaki City 253-0083, Kanagawa, JapanDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City 252-0374, Kanagawa, JapanDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City 252-0374, Kanagawa, JapanDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City 252-0374, Kanagawa, JapanDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City 252-0374, Kanagawa, JapanDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City 252-0374, Kanagawa, JapanDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City 252-0374, Kanagawa, JapanDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City 252-0374, Kanagawa, JapanDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City 252-0374, Kanagawa, JapanDepartment of Orthopedic Surgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Kawasaki City 216-8511, Kanagawa, JapanDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City 252-0374, Kanagawa, JapanDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City 252-0374, Kanagawa, JapanAnimal studies suggest that pain-related-molecule upregulation in degenerated intervertebral discs (IVDs) potentially leads to low back pain (LBP). We hypothesized that IVD mechanical stress and axial loading contribute to discogenic LBP’s pathomechanism. This study aimed to elucidate the relationships among the clinical findings, radiographical findings, and pain-related-molecule expression in human degenerated IVDs. We harvested degenerated-IVD samples from 35 patients during spinal interbody fusion surgery. Pain-related molecules including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, calcitonin gene-related peptide (CGRP), microsomal prostaglandin E synthase-1 (mPGES1), and nerve growth factor (NGF) were determined. We also recorded preoperative clinical findings including body mass index (BMI), Oswestry Disability Index (ODI), and radiographical findings including the vacuum phenomenon (VP) and spinal instability. Furthermore, we compared pain-related-molecule expression between the VP (−) and (+) groups. BMI was significantly correlated with the ODI, CGRP, and mPGES-1 levels. In the VP (+) group, mPGES-1 levels were significantly higher than in the VP (−) group. Additionally, CGRP and mPGES-1 were significantly correlated. Axial loading and mechanical stress correlated with CGRP and mPGES-1 expression and not with inflammatory cytokine or NGF expression. Therefore, axial loading and mechanical stress upregulate CGRP and mPGES-1 in human degenerated IVDs, potentially leading to chronic discogenic LBP.https://www.mdpi.com/1422-0067/23/6/2973discogenic low back paincalcitonin gene-related peptidemicrosomal prostaglandin E synthase-1
spellingShingle Masayuki Miyagi
Kentaro Uchida
Sho Inoue
Shotaro Takano
Mitsufumi Nakawaki
Ayumu Kawakubo
Hiroyuki Sekiguchi
Toshiyuki Nakazawa
Takayuki Imura
Wataru Saito
Eiki Shirasawa
Akiyoshi Kuroda
Shinsuke Ikeda
Yuji Yokozeki
Yusuke Mimura
Tsutomu Akazawa
Masashi Takaso
Gen Inoue
A High Body Mass Index and the Vacuum Phenomenon Upregulate Pain-Related Molecules in Human Degenerated Intervertebral Discs
International Journal of Molecular Sciences
discogenic low back pain
calcitonin gene-related peptide
microsomal prostaglandin E synthase-1
title A High Body Mass Index and the Vacuum Phenomenon Upregulate Pain-Related Molecules in Human Degenerated Intervertebral Discs
title_full A High Body Mass Index and the Vacuum Phenomenon Upregulate Pain-Related Molecules in Human Degenerated Intervertebral Discs
title_fullStr A High Body Mass Index and the Vacuum Phenomenon Upregulate Pain-Related Molecules in Human Degenerated Intervertebral Discs
title_full_unstemmed A High Body Mass Index and the Vacuum Phenomenon Upregulate Pain-Related Molecules in Human Degenerated Intervertebral Discs
title_short A High Body Mass Index and the Vacuum Phenomenon Upregulate Pain-Related Molecules in Human Degenerated Intervertebral Discs
title_sort high body mass index and the vacuum phenomenon upregulate pain related molecules in human degenerated intervertebral discs
topic discogenic low back pain
calcitonin gene-related peptide
microsomal prostaglandin E synthase-1
url https://www.mdpi.com/1422-0067/23/6/2973
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