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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 -
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 -
British Journal of Clinical Pharmacology Jun 2019Disorders of the skeleton are frequently accompanied by bone pain and a decline in the functional status of the patient. Bone pain occurs following a variety of injuries... (Review)
Review
Disorders of the skeleton are frequently accompanied by bone pain and a decline in the functional status of the patient. Bone pain occurs following a variety of injuries and diseases including bone fracture, osteoarthritis, low back pain, orthopedic surgery, fibrous dysplasia, rare bone diseases, sickle cell disease and bone cancer. In the past 2 decades, significant progress has been made in understanding the unique population of sensory and sympathetic nerves that innervate bone and the mechanisms that drive bone pain. Following physical injury of bone, mechanotranducers expressed by sensory nerve fibres that innervate bone are activated and sensitized so that even normally non-noxious loading or movement of bone is now being perceived as noxious. Injury of the bone also causes release of factors that; directly excite and sensitize sensory nerve fibres, upregulate proalgesic neurotransmitters, receptors and ion channels expressed by sensory neurons, induce ectopic sprouting of sensory and sympathetic nerve fibres resulting in a hyper-innervation of bone, and central sensitization in the brain that amplifies pain. Many of these mechanisms appear to be involved in driving both nonmalignant and malignant bone pain. Results from human clinical trials suggest that mechanism-based therapies that attenuate one type of bone pain are often effective in attenuating pain in other seemingly unrelated bone diseases. Understanding the specific mechanisms that drive bone pain in different diseases and developing mechanism-based therapies to control this pain has the potential to fundamentally change the quality of life and functional status of patients suffering from bone pain.
Topics: Age Factors; Analgesics; Animals; Bone and Bones; Central Nervous System Sensitization; Chemoreceptor Cells; Humans; Longevity; Mechanoreceptors; Musculoskeletal Pain; Pain Perception; Pain Threshold; Quality of Life; Risk Factors; Sympathetic Nervous System
PubMed: 30357885
DOI: 10.1111/bcp.13801 -
Journal of Bone and Mineral Metabolism May 2023Bone metastases frequently occur in patients with cancer. Skeletal-related events (SREs), including pain, impaired mobility, hypercalcemia, pathological fracture, spinal... (Review)
Review
Bone metastases frequently occur in patients with cancer. Skeletal-related events (SREs), including pain, impaired mobility, hypercalcemia, pathological fracture, spinal cord and nerve root compression, and bone marrow infiltration, can decrease the quality of life of the patients and increase the risk of morbidity. The mechanism of pain due to bone metastasis is complicated and involves various interactions among tumor cells, bone cells, activated inflammatory cells, and bone-innervating neurons. Cancer pain due to bone metastasis can be crippling and a chronic state that causes sarcopenia. For pain management, it is important to diagnose whether the pain is based on background pain or breakthrough pain due to bone metastasis. In addition, the management goal of cancer pain due to bone metastasis is not only to achieve pain relief but also to prevent pain progression and SREs. Pain mechanisms should be applied to achieve optimal management. This review aims to discuss the mechanisms of cancer pain due to bone metastasis and review the recommended drug therapies.
Topics: Humans; Cancer Pain; Quality of Life; Bone Neoplasms; Bone and Bones; Pain
PubMed: 36418587
DOI: 10.1007/s00774-022-01382-y -
Seminars in Nuclear Medicine Mar 2022Amongst cancer patients, bone pain due to skeletal metastases is a major cause of morbidity. A number of beta-emitting radiopharmaceuticals have been used to provide... (Review)
Review
Amongst cancer patients, bone pain due to skeletal metastases is a major cause of morbidity. A number of beta-emitting radiopharmaceuticals have been used to provide internal radiotherapy of bone metastases and provide palliative pain relief. In this article we describe the different physical characteristics of the various beta emitting radionuclides which have been used in this clinical setting and the potential impact of differences in dose-rate on radiobiological outcomes. A detailed review of the biodistribution of these treatments, based on both in-vivo clinical investigations and post mortem autoradiography assessments is provided. These treatments result in physiological delivery of radiation doses to the target disease as well as to critical healthy organs. Particular attention is paid to the radiation doses received by normal bone tissue, bone marrow as well as metastatic bone disease. The underlying models of radiation transport within bone and bone marrow are reviewed alongside the practical steps that must be taken to acquire and analyse the information require for clinical dosimetry assessments. The role of whole body measurements, blood and faecal assays as well as both planar and tomographic gamma camera imaging are considered. In addition we review the rationale for allocating measured bone uptake between trabecular and cortical bone tissue. The difference between bone volume and bone surface seeking radiopharmaceuticals are also discussed. This review also extends to the development of preclinical models of bone metastases which may inform future dosimetric calculations. Finally, we also present a comprehensive review of the dosimetry of the established treatments Strontium-chloride; Phosphorus; Rhenium-hydroxyethylidine disphosphonate; Rhenium-1,1-hydroxyethylidene disphosphonate (Re-HEDP); Samarium-ethylenediaminetetramethylene phosphonate; as well as the emerging treatments Rhenium-zoledronic acid; Rhenium-ibedronat; Lutetium-zoledronic acid; and Lutetium ethylenediaminetetramethylene phosphonate. This review highlights not only the inter treatment differences in the radiation absorbed doses delivered to metastatic disease by different radiopharmaceuticals but also the intra treatment differences which result in a large range of observed doses between patients.
Topics: Bone Neoplasms; Bone and Bones; Humans; Lutetium; Pain; Radiopharmaceuticals; Rhenium; Tissue Distribution; Zoledronic Acid
PubMed: 34895886
DOI: 10.1053/j.semnuclmed.2021.11.005 -
Journal of Bone and Mineral Research :... Aug 2019The innervation of bone has been described for centuries, and our understanding of its function has rapidly evolved over the past several decades to encompass roles of... (Review)
Review
The innervation of bone has been described for centuries, and our understanding of its function has rapidly evolved over the past several decades to encompass roles of subtype-specific neurons in skeletal homeostasis. Current research has been largely focused on the distribution and function of specific neuronal populations within bone, as well as their cellular and molecular relationships with target cells in the bone microenvironment. This review provides a historical perspective of the field of skeletal neurobiology that highlights the diverse yet interconnected nature of nerves and skeletal health, particularly in the context of bone anabolism and pain. We explore what is known regarding the neuronal subtypes found in the skeleton, their distribution within bone compartments, and their central projection pathways. This neuroskeletal map then serves as a foundation for a comprehensive discussion of the neural control of skeletal development, homeostasis, repair, and bone pain. Active synthesis of this research recently led to the first biotherapeutic success story in the field. Specifically, the ongoing clinical trials of anti-nerve growth factor therapeutics have been optimized to titrated doses that effectively alleviate pain while maintaining bone and joint health. Continued collaborations between neuroscientists and bone biologists are needed to build on this progress, leading to a more complete understanding of neural regulation of the skeleton and development of novel therapeutics. © 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.
Topics: Animals; Bone and Bones; Cellular Microenvironment; Humans; Neurons; Pain
PubMed: 31247122
DOI: 10.1002/jbmr.3822 -
Current Osteoporosis Reports Dec 2018The goal of this review is to provide a broad overview of the current understanding of mechanisms underlying bone and joint pain. (Review)
Review
PURPOSE OF REVIEW
The goal of this review is to provide a broad overview of the current understanding of mechanisms underlying bone and joint pain.
RECENT FINDINGS
Bone or joint pathology is generally accompanied by local release of pro-inflammatory cytokines, growth factors, and neurotransmitters that activate and sensitize sensory nerves resulting in an amplified pain signal. Modulation of the pain signal within the spinal cord and brain that result in net increased facilitation is proposed to contribute to the development of chronic pain. Great strides have been made in our understanding of mechanisms underlying bone and joint pain that will guide development of improved therapeutic options for these patients. Continued research is required for improved understanding of mechanistic differences driving different components of bone and/or joint pain such as movement related pain compared to persistent background pain. Advances will guide development of more individualized and comprehensive therapeutic options.
Topics: Arthralgia; Bone and Bones; Humans; Hyperalgesia; Joints; Nociception; Pain Measurement
PubMed: 30370434
DOI: 10.1007/s11914-018-0493-1 -
Current Opinion in Pharmacology Jun 2016Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease... (Review)
Review
Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease modifying agents and/or analgesics depending on the condition. Disease modifying agents affect the underlying pathophysiology of the disease and reduce as a secondary effect bone pain. Antiresorptive and anabolic agents, such as bisphosphonates and intermittent parathyroid hormone (1-34), respectively, have proven effective as pain relieving agents. Cathepsin K inhibitors and anti-sclerostin antibodies hold, due to their disease modifying effects, promise of a pain relieving effect. NSAIDs and opioids are widely employed in the treatment of bone pain. However, recent preclinical findings demonstrating a unique neuronal innervation of bone tissue and sprouting of sensory nerve fibers open for new treatment possibilities.
Topics: Analgesics; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bone Diseases; Bone and Bones; Chronic Pain; Humans; Knee Joint
PubMed: 26940053
DOI: 10.1016/j.coph.2016.02.007 -
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 -
Journal of Clinical Oncology : Official... Jun 2014Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic.... (Review)
Review
Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic. As detection and survival among patients with cancer have improved, pain has become an increasing challenge, because traditional therapies are often only partially effective. Until recently, knowledge of cancer pain mechanisms was poor compared with understanding of neuropathic and inflammatory pain states. We now view cancer-induced bone pain as a complex pain state involving components of both inflammatory and neuropathic pain but also exhibiting elements that seem unique to cancer pain. In addition, the pain state is often unpredictable, and the intensity of the pain is highly variable, making it difficult to manage. The establishment of translational animal models has started to reveal some of the molecular components involved in cancer pain. We present the essential pharmacologic and neurobiologic mechanisms involved in the generation and continuance of cancer-induced bone pain and discuss these in the context of understanding and treating patients. We discuss changes in peripheral signaling in the area of tumor growth, examine spinal cord mechanisms of sensitization, and finally address central processing. Our aim is to provide a mechanistic background for the sensory characteristics of cancer-induced bone pain as a basis for better understanding and treating this condition.
Topics: Animals; Bone and Bones; Humans; Neoplasms; Nociception; Pain
PubMed: 24799469
DOI: 10.1200/JCO.2013.51.7219