New Progress in Basic Research of Macrophages in the Pathogenesis and Treatment of Low Back Pain

Abstract

Low back pain (LBP) is quite common in clinical practice, which can lead to long-term bed rest or even disability. It is a worldwide health problem remains to be solved. LBP can be induced or exacerbated by abnormal structure and function of spinal tissue such as intervertebral disc (IVD), dorsal root ganglion (DRG) and muscle; IVD degeneration (IVDD) is considered as the most important among all the pathogenic factors. Inflammation, immune response, mechanical load, and hypoxia etc., can induce LBP by affecting the spinal tissue, among which inflammation and immune response are the key link. Inflammation and immune response play a double-edged sword role in LBP. As the main phagocytic cells in the body, macrophages are closely related to body homeostasis and various diseases. Recent studies have shown that macrophages are the only inflammatory cells that can penetrate the closed nucleus pulposus, expressed in various structures of the IVD, and the number is positively correlated with the degree of IVDD. Moreover, macrophages play a phagocytosis role or regulate the metabolism of DRG and muscle tissues through neuro-immune mechanism, while the imbalance of macrophages polarization will lead to more inflammatory factors to chemotaxis and aggregation, forming an “inflammatory waterfall” effect similar to “positive feedback,” which greatly aggravates LBP. Regulation of macrophages migration and polarization, inhibition of inflammation and continuous activation of immune response by molecular biological technology can markedly improve the inflammatory microenvironment, and thus effectively prevent and treat LBP. Studies on macrophages and LBP were mainly focused in the last 3–5 years, attracting more and more scholars’ attention. This paper summarizes the new research progress of macrophages in the pathogenesis and treatment of LBP, aiming to provide an important clinical prevention and treatment strategy for LBP.

Identifification and validation of ferroptosis signatures and immune infifiltration characteristics associated with intervertebral disc degeneration

“…The findings demonstrated that whereas eosinophils and Th2 cells reduced in the deteriorated nucleus pulposus compared to the normal group, the number of macrophages, CD8T cells, dendritic cells, and Th17 cells rose. The importance of macrophage infiltration in the etiology of IDD has been validated by recent research (Lan et al, 2022;Yan et al, 2022).…”

Engineered Human Intervertebral Disc Model Inducing Degenerative Microglial Proinflammation

“…This consideration leads to the hypothesis that human IVD cells may not be the sole contributors to the noxious and accelerating inflammatory responses found in degenerating IVD. Moreover, while the role of macrophage-mediated inflammation in IVD degeneration has been well demonstrated [ 32 , 33 , 34 ], little is known about how neuroinflammation, which can be mediated by microglia, is initiated and maintained in LBP.…”

“…First, in the probable mechanism of neuroinflammation initiation, diverse inflammatory responses are generally initiated by infiltration of immune cells, such as microglia, through invasive vascular structures. Indeed, most of the currently available studies support a positive correlation between increased innervation of the vascular/neuronal structure, discogenic pain, and inflammatory response [ 25 , 34 , 35 ]. Moreover, several studies have demonstrated that the degenerative IVD microenvironment includes infiltration and phenotypic switching of resident inflammatory-like cells, such as CD11b+, CD 68+, and CD4+ cells [ 2 , 32 , 36 , 37 , 38 ].…”

The Use of Medical Ozone in Chronic Intervertebral Disc Degeneration Can Be an Etiological and Conservative Treatment

“…The levels of these proinflammatory factors secreted by cells were found to be markedly elevated in IVDD, which promoted the degradation of extracellular matrix, facilitated the phenotype change of cells and resulted in an imbalance of catabolism and anabolism, thus leading to the occurrence of IVDD. M2 macrophages can secrete anti-inflammatory factors, such as IL-4, IL-1R, IL-10, TGF-β and PDGF, primarily playing anti-inflammatory and promoting tissue repair role [ 37 ]. M1 polarization of macrophages could promote inflammation and damage of NP cells and M2 polarization could be a therapeutic target [ 38 ].…”

“…IVDD is considered as a chronic inflammatory state. The non-surgical treatment only relieves the symptoms, and surgical treatment has the defects of recurrence, aggravation of adjacent segment degeneration and difficulty in restoring normal biological function of the spine [ 37 ]. Research groups have aimed to regulate the redox balance of disc cells as a therapeutic objective to alleviate oxidative stress.…”