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

Masayuki Miyagi,Takayuki Imura,Kentaro Uchida,Shotaro Takano,Toshiyuki Nakazawa,Akiyoshi Kuroda,Mitsufumi Nakawaki,Eiki Shirasawa,Yuji Yokozeki,Sho Inoue,Masashi Takaso,Hiroyuki Sekiguchi,Ayumu Kawakubo,Tsutomu Akazawa,Wataru Saito,Yusuke Mimura,Shinsuke Ikeda,Gen Inoue

doi:10.3390/ijms23062973

Abstract

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.

Highlights

Low back pain (LBP) is an important clinical issue, and the lifetime prevalence of low back pain (LBP) has been reported to be high and gradually increase as the aging society progresses [1]
To evaluate factors associated with mechanical stress and axial loading on intervertebral discs (IVDs), we focused on body mass index (BMI) and radiographical findings
BMI was significantly positively correlated with calcitonin gene-related peptide (CGRP) and microsomal prostaglandin E synthase-1 (r = 0.383, p = 0.028, and r = 0.383, p = 0.028, respectively)

Summary

Introduction

Low back pain (LBP) is an important clinical issue, and the lifetime prevalence of LBP has been reported to be high and gradually increase as the aging society progresses [1]. Regarding the pathomechanism of discogenic LBP, the expression of pain-related molecules is a potential pain-inducing factor. Several studies have shown pain-related molecules including inflammatory cytokines and prostaglandin E2 (PGE2) to be upregulated in herniated or degenerated human IVDs as well as animal models of degenerated. Nerve growth factor (NGF) and calcitonin gene-related peptide (CGRP) were identified as factors that play an important role in pain development. Developed CGRP antagonists and NGF inhibitors have been reported to be effective against pain diseases including headache and musculoskeletal pain [8,9]. We previously reported macrophage-derived inflammatory cytokines to regulate the expression of NGF and CGRP in IVD cells, potentially influencing LBP [10]. Various pain-related molecules in IVD cells could be associated with LBP development

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