Ivan Urits1, Alexander Capuco2, Medha Sharma3, Alan D Kaye4, Omar Viswanath5,6,7, Elyse M Cornett8, Vwaire Orhurhu9. 1. Beth Israel Deaconess Medical Center, Department of Anesthesia, Critical Care, and Pain Medicine, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA. iurits@bidmc.harvard.edu. 2. Georgetown University School of Medicine, Washington, DC, USA. 3. University of Pennsylvania School of Medicine, Philadelphia, PA, USA. 4. Department of Anesthesiology, Louisiana State University Health Sciences Center, New Orleans, LA, USA. 5. Valley Anesthesiology and Pain Consultants, Phoenix, AZ, USA. 6. Department of Anesthesiology, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA. 7. Department of Anesthesiology, School of Medicine, Creighton University, Omaha, NE, USA. 8. Department of Anesthesiology, Louisiana State University Health Shreveport, Shreveport, LA, USA. 9. Beth Israel Deaconess Medical Center, Department of Anesthesia, Critical Care, and Pain Medicine, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA.
Abstract
PURPOSE OF REVIEW: Discogenic low back pain (DLBP) stems from pathology in one or more intervertebral discs identified as the root cause of the pain. It is the most common type of chronic low back pain (LBP), representing 26-42% of attributable cases. RECENT FINDINGS: The clinical presentation of DLBP includes increased pain when sitting, coughing, or sneezing, and experiencing relief when standing or ambulating. Dermatomal radiation of pain to the lower extremity and neurological symptoms including numbness, motor weakness, and urinary or fecal incontinence are signs of advanced disease with disc prolapse, nerve root compression, or spinal stenosis. Degenerative disc disease is caused by both a decrease in disc nutrient supply causing decreased oxygen, lowered pH, and lessened ability of the intervertebral disc (IVD) to respond to increased load or injury; moreover, changes in the extracellular matrix composition cause weakening of the tissue and skewing the extracellular matrix's (ECM) harmonious balance between catabolic and anabolic factors for cell turnover in favor of catabolism. Thus, the degeneration of the disc causes a shift from type II to type I collagen expression by NP cells and a decrease in aggrecan synthesis leads to dehydrated matrix cells ultimately with loss of swelling pressure needed for mechanical support. Cell-based therapies such as autologous nucleus pulposus cell re-implantation have in animal models and human trials shown improvements in LBP score, retention of hydration in IVD, and increased disc height. Percutaneously delivered multipotent mesenchymal stem cell (MSC) therapy has been proposed as a potential means to uniquely ameliorate discogenic LBP holistically through three mechanisms: mitigation of primary nociceptive disc pain, slow or reversal of the catabolic metabolism, and restoration of disc tissue. Embryonic stem cells (ESCs) can differentiate into cells of all three germ layers in vitro, but their use is hindered related to ethical concerns, potential for immune rejection after transplantation, disease, and teratoma formation. Another similar approach to treating back pain is transplantation of the nucleus pulposus, which, like stem cell therapy, seeks to address the underlying cause of intervertebral disc degeneration by aiming to reverse the destructive inflammatory process and regenerate the proteoglycans and collagen found in healthy disc tissue. Preliminary animal models and clinical studies have shown mesenchymal stem cell implantation as a potential therapy for IVD regeneration and ECM restoration via a shift towards favorable anabolic balance and reduction of pain.
PURPOSE OF REVIEW: Discogenic low back pain (DLBP) stems from pathology in one or more intervertebral discs identified as the root cause of the pain. It is the most common type of chronic low back pain (LBP), representing 26-42% of attributable cases. RECENT FINDINGS: The clinical presentation of DLBP includes increased pain when sitting, coughing, or sneezing, and experiencing relief when standing or ambulating. Dermatomal radiation of pain to the lower extremity and neurological symptoms including numbness, motor weakness, and urinary or fecal incontinence are signs of advanced disease with disc prolapse, nerve root compression, or spinal stenosis. Degenerative disc disease is caused by both a decrease in disc nutrient supply causing decreased oxygen, lowered pH, and lessened ability of the intervertebral disc (IVD) to respond to increased load or injury; moreover, changes in the extracellular matrix composition cause weakening of the tissue and skewing the extracellular matrix's (ECM) harmonious balance between catabolic and anabolic factors for cell turnover in favor of catabolism. Thus, the degeneration of the disc causes a shift from type II to type I collagen expression by NP cells and a decrease in aggrecan synthesis leads to dehydrated matrix cells ultimately with loss of swelling pressure needed for mechanical support. Cell-based therapies such as autologous nucleus pulposus cell re-implantation have in animal models and human trials shown improvements in LBP score, retention of hydration in IVD, and increased disc height. Percutaneously delivered multipotent mesenchymal stem cell (MSC) therapy has been proposed as a potential means to uniquely ameliorate discogenic LBP holistically through three mechanisms: mitigation of primary nociceptive disc pain, slow or reversal of the catabolic metabolism, and restoration of disc tissue. Embryonic stem cells (ESCs) can differentiate into cells of all three germ layers in vitro, but their use is hindered related to ethical concerns, potential for immune rejection after transplantation, disease, and teratoma formation. Another similar approach to treating back pain is transplantation of the nucleus pulposus, which, like stem cell therapy, seeks to address the underlying cause of intervertebral disc degeneration by aiming to reverse the destructive inflammatory process and regenerate the proteoglycans and collagen found in healthy disc tissue. Preliminary animal models and clinical studies have shown mesenchymal stem cell implantation as a potential therapy for IVD regeneration and ECM restoration via a shift towards favorable anabolic balance and reduction of pain.
Authors: X Liu; D Krishnamoorthy; L Lin; P Xue; F Zhang; L Chi; R J Linhardt; J C Iatridis Journal: Eur Cell Mater Date: 2018-02-22 Impact factor: 3.942
Authors: Salomon Poliwoda; Nazir Noor; Evan Downs; Amanda Schaaf; Abigail Cantwell; Latha Ganti; Alan D Kaye; Luke I Mosel; Caroline B Carroll; Omar Viswanath; Ivan Urits Journal: Orthop Rev (Pavia) Date: 2022-08-25
Authors: Laura Baumgartner; Karin Wuertz-Kozak; Christine L Le Maitre; Francis Wignall; Stephen M Richardson; Judith Hoyland; Carlos Ruiz Wills; Miguel A González Ballester; Michael Neidlin; Leonidas G Alexopoulos; Jérôme Noailly Journal: Int J Mol Sci Date: 2021-01-12 Impact factor: 5.923
Authors: Jesil Kasamkattil; Anna Gryadunova; Ivan Martin; Andrea Barbero; Stefan Schären; Olga Krupkova; Arne Mehrkens Journal: Int J Mol Sci Date: 2022-02-25 Impact factor: 6.208
Authors: Andreas S Croft; Svenja Illien-Jünger; Sibylle Grad; Julien Guerrero; Sebastian Wangler; Benjamin Gantenbein Journal: Int J Mol Sci Date: 2021-03-29 Impact factor: 5.923