Search

Up until fairly recently, it was thought that sciatic pain in the lumbar herniated disc was caused by compression on the nerve root. However, the lumbar herniated disc shows mixed pictures which are difficult to explain by simple mechanical compromise. In recent years various immunology, immunohistochemistry and molecular biology studies have shown that the herniated tissue is not an inert material, but rather it Is biologically very active with the capability of expressing a series of inflammatory mediators: cytokines such as interleukin-1, interleukin-6, interleuquin-8 and tumor necrosis factor being the ones which stand out. The inflammation is not only induced by the chemical irritation of the bioactive substances released by the nucleus pulposus but also by an autoimmune response against itself. Thus, in addition to the mechanical factor, the biomechanical mediation plays an important role in the pathophysiology of sciatic pain and of radiculopathy. Through a review of a wide range of literature, we researched the cellular molecular mediators involved in this inflammatory process around the lumbar herniated disc and its involvement in sciatic pain., (Copyright © 2020 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.) more...

Background Context: Back pain is a highly prevalent health problem in the world today and has a great economic impact on health-care budgets. Intervertebral disc (IVD) degeneration has been identified as a main cause of back pain. Inflammatory cytokines produced by macrophages or disc cells in an inflammatory environment play an important role in painful progressive degeneration of IVD. Mesenchymal stem cells (MSCs) have shown to have immunosuppressive and anti-inflammatory properties. Mesenchymal stem cells express a variety of chemokines and cytokines receptors having tropism to inflammation sites., Purpose: This study aimed to develop an in vitro controlled and standardized model of inflammation and degeneration of IVD with rat cells and to evaluate the protective and immunomodulatory effect of conditioned medium (CM) from the culture of MSCs to improve the conditions presented in herniated disc and discogenic pain processes., Study Design: This is an experimental study., Methods: In this study, an in vitro model of inflammation and degeneration of IVD has been developed, as well as the effectiveness of CM from the culture of MSCs., Results: Conditioned medium from MSCs downregulated the expression of various proinflammatory cytokines produced in the pathogenesis of discogenic pain such as interleukin (IL)-1β, IL-6, IL-17, and tumor necrosis factor (TNF)., Conclusion: Mesenchymal stem cells represent a promising alternative strategy in the treatment of IVD degeneration inasmuch as there is currently no treatment which leads to a complete remission of long-term pain in the absence of drugs., (Copyright © 2017 Elsevier Inc. All rights reserved.) more...

The intervertebral disc (IVD) is noted for its low cell content, and being the largest avascular structure of human body. The low amount of cells in the disc have to adapt to an anaerobic metabolism with low oxygen pressure and acidic pH. Apart from surviving in an adverse microenvironment, they are exposed to a high level of mechanical stress. The biological adaptation of cells to acidosis and hyperosmolarity conditions are regulated by mechanoproteins, which are responsible for converting a mechanical signal into a cellular response, thus modifying its gene expression. Mechanobiology helps us to better understand the pathophysiology of IVD and its potential biological repair., (Copyright © 2016 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.) more...

The cells of the intervertebral disc (IVD) have an unusual acidic and hyperosmotic microenvironment. They express acid-sensing ion channels (ASICs), gated by extracellular protons and mechanical forces, as well as neurotrophins and their signalling receptors. In the nervous tissues some neurotrophins regulate the expression of ASICs. The expression of ASIC2 and TrkB in human normal and degenerated IVD was assessed using quantitative-PCR, Western blot, and immunohistochemistry. Moreover, we investigated immunohistochemically the expression of ASIC2 in the IVD of TrkB-deficient mice. ASIC2 and TrkB mRNAs were found in normal human IVD and both increased significantly in degenerated IVD. ASIC2 and TrkB proteins were also found co-localized in a variable percentage of cells, being significantly higher in degenerated IVD than in controls. The murine IVD displayed ASIC2 immunoreactivity which was absent in the IVD of TrkB-deficient mice. Present results demonstrate the occurrence of ASIC2 and TrkB in the human IVD, and the increased expression of both in pathological IVD suggest their involvement in IVD degeneration. These data also suggest that TrkB-ligands might be involved in the regulation of ASIC2 expression, and therefore in mechanisms by which the IVD cells accommodate to low pH and hypertonicity. more...

Acid-sensing ion channels (ASICs) are a family of H(+)-gated voltage-insensitive ion channels that respond to extracellular acidification by regulating transmembrane Ca(2+) flux. Moreover, ASICs can also be gated by mechanical forces and may function as mechanosensors. The cells of the intervertebral disc (IVD) have an unusual acidic and hyperosmotic microenvironment. Changes in the pH and osmolarity determine the viability of IVD cells and the composition of the extracellular matrix, and both are the basis of IVD degeneration. In this study, the expression of ASICs (ASIC1, ASIC2, ASIC3 and ASIC4) mRNAs and proteins in human healthy and degenerated IVD was evaluated by quantitative reverse transcription-quantitative polymerase chain reaction and Western blot. The distribution of ASIC proteins was determined by immunohistochemistry. The mRNAs for all ASICs were detected in normal human IVD, and significantly increased levels were found in degenerated IVD. Western blots demonstrated the presence of proteins with estimated molecular weights of approximately 68-72 kDa. In both the annulus fibrosus (AF) and nucleus pulposus (NP) of normal IVD, ASIC2 is the most frequently expressed ASIC followed by ASIC3, ASIC1 and ASIC4. In the AF of degenerated IVD, there was a significant increase in the number of ASIC1 and ASIC4 positive cells, whereas in the NP, we found significant increase of expression of ASIC1, ASIC2 and ASIC3. These results describe the occurrence and localization of different ASICs in human healthy IVD, and their increased expression in degenerated IVD, thus suggesting that ASICs may be involved in IVD degeneration. more...

Until very recently, intervertebral disc innervation was a subject of considerable debate. Nowadays, the introduction of inmunohistochemical techniques associated to specific antibodies and studies with retrograde tracers in nerves have allowed greater understanding of disc innervation in physiological and pathological conditions and also endings characteristics and their patterns of distribution in both situations. The existing controversies regarding structural basis of discogenic pain, have raised the interest of knowing the influence of innervation in back pain from discal origin and its characteristics. Today, we know that pathologic neoinnervation accompanying radial fissures is an important factor in the genesis of discogenic pain; within a complex mechanism in which other neurobiomechemical, inflammatory and biomechanical factors are involved., (Copyright © 2012 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.) more...

The normal intervertebral disc (IVD) is a poorly innervated organ supplied only by sensory (mainly nociceptive) and postganglionic sympathetic (vasomotor efferents) nerve fibers. Interestingly, upon degeneration, the IVD becomes densely innervated even in regions that in normal conditions lack innervation. This increased innervation has been associated with pain of IVD origin. The mechanisms responsible for nerve growth and hyperinnervation of pathological IVDs have not been fully elucidated. Among the molecules that are presumably involved in this process are some members of the family of neurotrophins (NTs), which are known to have both neurotrophic and neurotropic properties and regulate the density and distribution of nerve fibers in peripheral tissues. NTs and their receptors are expressed in healthy IVDs but much higher levels have been observed in pathological IVDs, thus suggesting a correlation between levels of expression of NTs and density of innervation in IVDs. In addition, NTs also play a role in inflammatory responses and pain transmission by increasing the expression of pain-related peptides and modulating synapses of nociceptive neurons at the spinal cord. This article reviews current knowledge about the innervation of IVDs, NTs and NT receptors, expression of NTs and their receptors in IVDs as well as in the sensory neurons innervating the IVDs, the proinflammatory role of NTs, NTs as nociception regulators, and the potential network of discogenic pain involving NTs. more...