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Physiological Reviews Jul 2021Skeletal metastases are frequent complications of many cancers, causing bone complications (fractures, bone pain, disability) that negatively affect the patient's... (Review)
Review
Skeletal metastases are frequent complications of many cancers, causing bone complications (fractures, bone pain, disability) that negatively affect the patient's quality of life. Here, we first discuss the burden of skeletal complications in cancer bone metastasis. We then describe the pathophysiology of bone metastasis. Bone metastasis is a multistage process: long before the development of clinically detectable metastases, circulating tumor cells settle and enter a dormant state in normal vascular and endosteal niches present in the bone marrow, which provide immediate attachment and shelter, and only become active years later as they proliferate and alter the functions of bone-resorbing (osteoclasts) and bone-forming (osteoblasts) cells, promoting skeletal destruction. The molecular mechanisms involved in mediating each of these steps are described, and we also explain how tumor cells interact with a myriad of interconnected cell populations in the bone marrow, including a rich vascular network, immune cells, adipocytes, and nerves. We discuss metabolic programs that tumor cells could engage with to specifically grow in bone. We also describe the progress and future directions of existing bone-targeted agents and report emerging therapies that have arisen from recent advances in our understanding of the pathophysiology of bone metastases. Finally, we discuss the value of bone turnover biomarkers in detection and monitoring of progression and therapeutic effects in patients with bone metastasis.
Topics: Animals; Biomarkers; Bone Density Conservation Agents; Bone Neoplasms; Bone and Bones; Denosumab; Humans
PubMed: 33356915
DOI: 10.1152/physrev.00012.2019 -
International Journal of Molecular... Dec 2022Intervertebral disc (IVD) degeneration is a major contributing factor for discogenic low back pain (LBP), causing a significant global disability. The IVD consists of an... (Review)
Review
Intervertebral disc (IVD) degeneration is a major contributing factor for discogenic low back pain (LBP), causing a significant global disability. The IVD consists of an inner core proteoglycan-rich nucleus pulposus (NP) and outer lamellae collagen-rich annulus fibrosus (AF) and is confined by a cartilage end plate (CEP), providing structural support and shock absorption against mechanical loads. Changes to degenerative cascades in the IVD cause dysfunction and instability in the lumbar spine. Various treatments include pharmacological, rehabilitation or surgical interventions that aim to relieve pain; however, these modalities do not halt the pathologic events of disc degeneration or promote tissue regeneration. Loss of stem and progenitor markers, imbalance of the extracellular matrix (ECM), increase of inflammation, sensory hyperinnervation and vascularization, and associated signaling pathways have been identified as the onset and progression of disc degeneration. To better understand the pain originating from IVD, our review focuses on the anatomy of IVD and the pathophysiology of disc degeneration that contribute to the development of discogenic pain. We highlight the key mechanisms and associated signaling pathways underlying disc degeneration causing discogenic back pain, current clinical treatments, clinical perspective and directions of future therapies. Our review comprehensively provides a better understanding of healthy IVD and degenerative events of the IVD associated with discogenic pain, which helps to model painful disc degeneration as a therapeutic platform and to identify signaling pathways as therapeutic targets for the future treatment of discogenic pain.
Topics: Humans; Intervertebral Disc Degeneration; Low Back Pain; Annulus Fibrosus; Cartilage; Back Pain; Intervertebral Disc
PubMed: 36613651
DOI: 10.3390/ijms24010208 -
Deutsches Arzteblatt International Dec 2017For many years, low back pain has been both the leading cause of days lost from work and the leading indication for medical rehabilitation. The goal of the German... (Review)
Review
BACKGROUND
For many years, low back pain has been both the leading cause of days lost from work and the leading indication for medical rehabilitation. The goal of the German Disease Management Guideline (NDMG) on nonspecific low back pain is to improve the treatment of patients with this condition.
METHODS
The current update of the NDMG on non-specific low back pain is based on articles retrieved by a systematic search of the literature for systematic reviews. Its recommendations for diagnosis and treatment were developed by a collaborative effort of 29 scientific medical societies and organizations and approved in a formal consensus process.
RESULTS
If the history and physical examination do not arouse any suspicion of a dangerous underlying cause, no further diagnostic evaluation is indicated for the time being. Passive, reactive measures should be taken only in combination with activating measures, or not at all. When drugs are used for symptomatic treatment, patients should be treated with the most suitable drug in the lowest possible dose and for as short a time as possible.
CONCLUSION
A physician should be in charge of the overall care process. The patient should be kept well informed over the entire course of his or her illness and should be encouraged to adopt a healthful lifestyle, including regular physical exercise.
Topics: Exercise Therapy; Germany; Humans; Low Back Pain; Lumbar Vertebrae; Practice Guidelines as Topic; Prospective Studies
PubMed: 29321099
DOI: 10.3238/arztebl.2017.0883 -
Acta Orthopaedica Dec 2016The extent of ageing in the musculoskeletal system during the life course affects the quality and length of life. Loss of bone, degraded articular cartilage, and... (Review)
Review
The extent of ageing in the musculoskeletal system during the life course affects the quality and length of life. Loss of bone, degraded articular cartilage, and degenerate, narrowed intervertebral discs are primary features of an ageing skeleton, and together they contribute to pain and loss of mobility. This review covers the cellular constituents that make up some key components of the musculoskeletal system and summarizes discussion from the 2015 Aarhus Regenerative Orthopaedic Symposium (AROS) (Regeneration in the Ageing Population) about how each particular cell type alters within the ageing skeletal microenvironment.
Topics: Aging; Bone and Bones; Cartilage, Articular; Cellular Senescence; Chondrocytes; Humans; Intervertebral Disc; Musculoskeletal System
PubMed: 27748151
DOI: 10.1080/17453674.2016.1244750 -
Journal of Advanced Research Jan 2022Cancer-induced Bone Pain (CIBP) is an important factor affecting their quality of life of cancer survivors. In addition, current clinical practice and scientific... (Review)
Review
BACKGROUND
Cancer-induced Bone Pain (CIBP) is an important factor affecting their quality of life of cancer survivors. In addition, current clinical practice and scientific research suggest that neuropathic pain is a representative component of CIBP. However, given the variability of cancer conditions and the complexity of neuropathic pain, related mechanisms have been continuously supplemented but have not been perfected.
AIM OF REVIEW
Therefore, the current review highlights the latest progress in basic research on the field and proposes potential therapeutic targets, representative drugs and upcoming therapies.
KEY SCIENTIFIC CONCEPTS OF REVIEW
Notably, factors such as central sensitization, neuroinflammation, glial cell activation and an acidic environment are considered to be related to neuropathic pain in CIBP. Nonetheless, further research is needed to ascertain the mechanism of CIBP in order to develop highly effective drugs. Moreover, more attention needs to be paid to the care of patients with advanced cancer.
Topics: Bone Neoplasms; Bone and Bones; Cancer Pain; Humans; Neuroinflammatory Diseases; Quality of Life
PubMed: 35003797
DOI: 10.1016/j.jare.2021.06.006 -
Annals of the Rheumatic Diseases Apr 2021Osteoarthritis (OA) is a degenerative joint disease in the elderly. Although OA has been considered as primarily a disease of the articular cartilage, the participation... (Review)
Review
Osteoarthritis (OA) is a degenerative joint disease in the elderly. Although OA has been considered as primarily a disease of the articular cartilage, the participation of subchondral bone in the pathogenesis of OA has attracted increasing attention. This review summarises the microstructural and histopathological changes in subchondral bone during OA progression that are due, at the cellular level, to changes in the interactions among osteocytes, osteoblasts, osteoclasts (OCs), endothelial cells and sensory neurons. Therefore, we focus on how pathological cellular interactions in the subchondral bone microenvironment promote subchondral bone destruction at different stages of OA progression. In addition, the limited amount of research on the communication between OCs in subchondral bone and chondrocytes (CCs) in articular cartilage during OA progression is reviewed. We propose the concept of 'OC-CC crosstalk' and describe the various pathways by which the two cell types might interact. Based on the 'OC-CC crosstalk', we elaborate potential therapeutic strategies for the treatment of OA, including restoring abnormal subchondral bone remodelling and blocking the bridge-subchondral type H vessels. Finally, the review summarises the current understanding of how the subchondral bone microenvironment is related to OA pain and describes potential interventions to reduce OA pain by targeting the subchondral bone microenvironment.
Topics: Aged; Bone and Bones; Cartilage, Articular; Endothelial Cells; Humans; Osteoarthritis; Pain
PubMed: 33158879
DOI: 10.1136/annrheumdis-2020-218089 -
Current Osteoporosis Reports Aug 2018This paper describes recent advances in understanding the mechanisms that drive fracture pain and how these findings are helping develop new therapies to treat fracture... (Review)
Review
PURPOSE OF REVIEW
This paper describes recent advances in understanding the mechanisms that drive fracture pain and how these findings are helping develop new therapies to treat fracture pain.
RECENT FINDINGS
Immediately following fracture, mechanosensitive nerve fibers that innervate bone are mechanically distorted. This results in these nerve fibers rapidly discharging and signaling the initial sharp fracture pain to the brain. Within minutes to hours, a host of neurotransmitters, cytokines, and nerve growth factor are released by cells at the fracture site. These factors stimulate, sensitize, and induce ectopic nerve sprouting of the sensory and sympathetic nerve fibers which drive the sharp pain upon movement and the dull aching pain at rest. If rapid and effective healing of the fracture occurs, these factors return to baseline and the pain subsides, but if not, these factors can drive chronic bone pain. New mechanism-based therapies have the potential to fundamentally change the way acute and chronic fracture pain is managed.
Topics: Acute Pain; Analgesics, Opioid; Animals; Bone and Bones; Central Nervous System Sensitization; Chronic Pain; Disease Models, Animal; Fracture Healing; Fractures, Bone; Humans; Neuralgia; Nociceptive Pain; Nociceptors; Pain Management; Peripheral Nerve Injuries; Sensory Receptor Cells
PubMed: 29948820
DOI: 10.1007/s11914-018-0446-8 -
Medicine Sep 2022The purpose of this study was to investigate the effects of resistance exercise in comparison with those of common exercise on chronic neck pain (CNP) to provide useful... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The purpose of this study was to investigate the effects of resistance exercise in comparison with those of common exercise on chronic neck pain (CNP) to provide useful clinical guidelines for reducing pain or increasing cervical range of motion (ROM), upper trapezius tone, disability level, and quality of life (QOL).
METHODS
The subjects were randomized into a cervical and scapula-focused resistance exercise group (CSREG, n = 21) or trapezius massage group (TMG, n = 20). All groups received a 4-week, five times per week CSRE or TM program for CNP. The visual analogue scale (VAS) score, cervical ROM, myotonometer measures (upper trapezius tone, stiffness, and elasticity), neck disability index (NDI), and short form-36 (SF-36) were identified as the primary outcomes.
RESULTS
Within-group changes in VAS, cervical ROM, myotonometer measures, NDI, and SF-36 were significant in the CSREG and TMG (P < .05). The between-group changes in VAS, cervical rotation, myotonometer (upper trapezius tone and stiffness), NDI, and SF-36 after intervention showed significant differences between the CSREG and TMG (P < .05).
CONCLUSION
These results suggest that the CSRE program is effective in improving pain, cervical ROM, upper trapezius tone, disability level, and QOL in patients with CNP. More comprehensive studies with longer follow-up durations are needed to better understand the potential effects of the CSRE program in patients with CNP.
Topics: Cervical Vertebrae; Chronic Pain; Humans; Massage; Neck Pain; Quality of Life; Range of Motion, Articular; Resistance Training; Scapula; Superficial Back Muscles; Treatment Outcome
PubMed: 36181044
DOI: 10.1097/MD.0000000000030887 -
European Spine Journal : Official... Nov 2016Low back pain (LBP) is the most disabling condition worldwide. Although LBP relates to different spinal pathologies, vertebral bone marrow lesions visualized as Modic... (Review)
Review
PURPOSE
Low back pain (LBP) is the most disabling condition worldwide. Although LBP relates to different spinal pathologies, vertebral bone marrow lesions visualized as Modic changes on MRI have a high specificity for discogenic LBP. This review summarizes the pathobiology of Modic changes and suggests a disease model.
METHODS
Non-systematic literature review.
RESULTS
Chemical and mechanical stimulation of nociceptors adjacent to damaged endplates are likely a source of pain. Modic changes are adjacent to a degenerated intervertebral disc and have three generally interconvertible types suggesting that the different Modic change types represent different stages of the same pathological process, which is characterized by inflammation, high bone turnover, and fibrosis. A disease model is suggested where disc/endplate damage and the persistence of an inflammatory stimulus (i.e., occult discitis or autoimmune response against disc material) create predisposing conditions. The risk to develop Modic changes likely depends on the inflammatory potential of the disc and the capacity of the bone marrow to respond to it. Bone marrow lesions in osteoarthritic knee joints share many characteristics with Modic changes adjacent to degenerated discs and suggest that damage-associated molecular patterns and marrow fat metabolism are important pathogenetic factors. There is no consensus on the ideal therapy. Non-surgical treatment approaches including intradiscal steroid injections, anti-TNF-α antibody, antibiotics, and bisphosphonates have some demonstrated efficacy in mostly non-replicated clinical studies in reducing Modic changes in the short term, but with unknown long-term benefits. New diagnostic tools and animal models are required to improve painful Modic change identification and classification, and to clarify the pathogenesis.
CONCLUSION
Modic changes are likely to be more than just a coincidental imaging finding in LBP patients and rather represent an underlying pathology that should be a target for therapy.
Topics: Bone Marrow; Humans; Intervertebral Disc; Low Back Pain; Lumbar Vertebrae; Magnetic Resonance Imaging; Models, Biological
PubMed: 26914098
DOI: 10.1007/s00586-016-4459-7 -
International Journal of Molecular... Feb 2020Degenerative disc disease is a leading cause of chronic back pain in the aging population in the world. Sinuvertebral nerve and basivertebral nerve are postulated to be... (Review)
Review
Lumbar Degenerative Disease Part 1: Anatomy and Pathophysiology of Intervertebral Discogenic Pain and Radiofrequency Ablation of Basivertebral and Sinuvertebral Nerve Treatment for Chronic Discogenic Back Pain: A Prospective Case Series and Review of Literature.
Degenerative disc disease is a leading cause of chronic back pain in the aging population in the world. Sinuvertebral nerve and basivertebral nerve are postulated to be associated with the pain pathway as a result of neurotization. Our goal is to perform a prospective study using radiofrequency ablation on sinuvertebral nerve and basivertebral nerve; evaluating its short and long term effect on pain score, disability score and patients' outcome. A review in literature is done on the pathoanatomy, pathophysiology and pain generation pathway in degenerative disc disease and chronic back pain. 30 patients with 38 levels of intervertebral disc presented with discogenic back pain with bulging degenerative intervertebral disc or spinal stenosis underwent Uniportal Full Endoscopic Radiofrequency Ablation application through either Transforaminal or Interlaminar Endoscopic Approaches. Their preoperative characteristics are recorded and prospective data was collected for Visualized Analogue Scale, Oswestry Disability Index and MacNab Criteria for pain were evaluated. There was statistically significant Visual Analogue Scale improvement from preoperative state at post-operative 1wk, 6 months and final follow up were 4.4 ± 1.0, 5.5 ± 1.2 and 5.7 ± 1.3, respectively, < 0.0001. Oswestery Disability Index improvement from preoperative state at 1week, 6 months and final follow up were 45.8 ± 8.7, 50.4 ± 8.2 and 52.7 ± 10.3, < 0.0001. MacNab criteria showed excellent outcomes in 17 cases, good outcomes in 11 cases and fair outcomes in 2 cases Sinuvertebral Nerve and Basivertebral Nerve Radiofrequency Ablation is effective in improving the patients' pain, disability status and patient outcome in our study.
Topics: Adolescent; Adult; Aged; Back Pain; Catheter Ablation; Chronic Pain; Female; Humans; Intervertebral Disc Degeneration; Lumbar Vertebrae; Male; Middle Aged; Prospective Studies; Spinal Nerves
PubMed: 32098249
DOI: 10.3390/ijms21041483