Bone pain (also known medically by several other names) is

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

coming from a

bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...

, and is caused by damaging stimuli. It occurs as a result of a wide range of diseases or physical conditions or both, and may severely impair the quality of life.Luger, N. Mach, D. Sevcik, M. Mantyh, P. (2005). Bone cancer pain: From mechanism to model to therapy. ''Journal of Pain and Symptom Management''. 29(5): 32-46. Bone pain belongs to the class of deep somatic

, often experienced as a dull pain that cannot be localized accurately by the patient. This is in contrast with the pain which is mediated by superficial receptors in, e.g., the skin. Bone pain can have several possible causes ranging from extensive physical stress to serious diseases such as

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

.Zwas, T. Elkanovitch, R. George, F. (1987). Interpretation and Classification of Bone Scintigraphic Findings in Stress Fractures. ''Journal of Nuclear Medicine''. 28: 452-457.Mantyh, P. Clohisy, D. Koltzenburg, M. Hunt, S. (2002). Molecular Mechanism of Cancer Pain. ''Nature Reviews Cancer''. 2: 201-209. For many years, it has been known that bones are innervated with sensory

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

s, yet their exact anatomy remained obscure due to the contrasting physical properties of bone and neural tissue.McCredie J (2007). Nerves in bone: the silent partners. ''Skeletal Radiology''. 36: 473–475. More recently, it is becoming clear what types of nerves innervated which sections of bone.Mach, D. Rogers, S. Sabino, M. Luger, N. Schwei, M. Pomonis, J. Keyser, C. Clohisy, D. Adams, D. O'leary, P. Mantyh, P. (2002). Origins of skeletal pain: Sensory and sympathetic innervation of the mouse femur. ''Neuroscience''. 113(1):155-166. The periosteal layer of bone tissue is highly pain-sensitive and an important cause of pain in several disease conditions causing bone pain, like

fracture Fracture is the separation of an object or material into two or more pieces under the action of stress. The fracture of a solid usually occurs due to the development of certain displacement discontinuity surfaces within the solid. If a displa ...

osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...

, etc. However, in certain diseases, the

endosteal The endosteum (plural endostea) is a thin vascular membrane of connective tissue that lines the inner surface of the bony tissue that forms the medullary cavity of long bones. This endosteal surface is usually resorbed during long periods of ma ...

and haversian nerve supply seems to play an important role, e.g. in osteomalacia, osteonecrosis, and other bone diseases. Thus, there are several types of bone pain, each with many potential sources or origins of cause.

Causes

A number of diseases can cause bone pain, including the following: *

Endocrine The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...

, such as

hyperparathyroidism Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands (primary hyperparathyroidism) or as response to external stimuli (secondary hyperparathyroidism). ...

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

. * Gastrointestinal or

systemic Systemic fundamental to a predominant social, economic, or political practice. This refers to: In medicine In medicine, ''systemic'' means affecting the whole body, or at least multiple organ systems. It is in contrast with ''topical'' or ''loc ...

, such as celiac disease and non-celiac gluten sensitivity (both often occur without obvious digestive symptoms),

inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammation, inflammatory conditions of the colon (anatomy), colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine a ...

(including

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...

and ulcerative colitis). *

Hematologic Hematology ( always spelled haematology in British English) is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to blood. It involves treating diseases that affect the produc ...

, such as Cushing's syndrome, histiocytosis,

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, an ...

and

sickle cell anaemia Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blo ...

. * Infectious, such as

Lyme disease Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the ''Borrelia'' bacterium, which is spread by ticks in the genus ''Ixodes''. The most common sign of infection is an expanding red rash, known as erythema migran ...

and osteomyelitis. *

Neurological Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...

, such as

spinal cord injury A spinal cord injury (SCI) is damage to the spinal cord that causes temporary or permanent changes in its function. Symptoms may include loss of muscle function, sensation, or autonomic function in the parts of the body served by the spinal cor ...

and

vertebra The spinal column, a defining synapomorphy shared by nearly all vertebrates,Hagfish are believed to have secondarily lost their spinal column is a moderately flexible series of vertebrae (singular vertebra), each constituting a characteristic ...

l degeneration. * Oncologic, such as bone metastasis and

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

. * Rheumatic, such as

ankylosing spondylitis Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine typically where the spine joins the pelvis. Occasionally areas affected may include other joints such as the shoulders or hip ...

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...

gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intensit ...

. *Others, such as fractures,

, Paget's disease of bone (also termed osteitis deformans or just Paget's disease).

Causes in children

* Acute leukemia. *

Acute rheumatic fever Rheumatic fever (RF) is an inflammatory disease that can involve the heart, joints, skin, and brain. The disease typically develops two to four weeks after a streptococcal throat infection. Signs and symptoms include fever, multiple painful jo ...

, a very dangerous disease that can cause permanent cardiac damage. *Untreated celiac disease, which can present without gastrointestinal symptoms. *

Fibromyalgia Fibromyalgia (FM) is a medical condition defined by the presence of chronic widespread pain, fatigue, waking unrefreshed, cognitive symptoms, lower abdominal pain or cramps, and depression. Other symptoms include insomnia and a general hyp ...

, which affects people of all ages. * Growing pains. *

Hypermobility syndrome Hypermobility spectrum disorder (HSD), related to earlier diagnoses such as hypermobility syndrome (HMS), and joint hypermobility syndrome (JHS) is a heritable connective tissue disorder that affects joints and ligaments. Different forms and sub ...

can present with knee or ankle pain. *

Lupus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...

. *

Henoch–Schönlein purpura Henoch–Schönlein purpura (HSP), also known as IgA vasculitis, is a disease of the skin, mucous membranes, and sometimes other organs that most commonly affects children. In the skin, the disease causes palpable purpura (small, raised areas of bl ...

. *

Fibrous dysplasia of bone Fibrous dysplasia is a disorder where normal bone and marrow is replaced with fibrous tissue, resulting in formation of bone that is weak and prone to expansion. As a result, most complications result from fracture, deformity, functional impairme ...

. *

Infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...

. *

Injury An injury is any physiological damage to living tissue caused by immediate physical stress. An injury can occur intentionally or unintentionally and may be caused by blunt trauma, penetrating trauma, burning, toxic exposure, asphyxiation, o ...

such as a

. *

Inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammation, inflammatory conditions of the colon (anatomy), colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine a ...

. * Juvenile idiopathic arthritis. *

Legg–Calvé–Perthes disease Legg–Calvé–Perthes disease (LCPD) is a childhood hip disorder initiated by a disruption of blood flow to the head of the femur. Due to the lack of blood flow, the bone dies (osteonecrosis or avascular necrosis) and stops growing. Over time, ...

. *

, which is transmitted by ticks and is characterized by debilitating polyarthritis, neurologic symptoms, and erythema migrans. *

Lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...

. * Osteomalacia/ rickets in adolescents. * Osteopetrosis. * Osteosarcoma. * Rickets. * Septic arthritis, a severe infection of the joint that can lead to permanent joint damage. * Spondyloarthropathies. *

Viral Viral means "relating to viruses" (small infectious agents). Viral may also refer to: Viral behavior, or virality Memetic behavior likened that of a virus, for example: * Viral marketing, the use of existing social networks to spread a marke ...

diseases, including the

measles Measles is a highly contagious infectious disease caused by measles virus. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often greater than , cough, ...

influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...

, mononucleosis,

chickenpox Chickenpox, also known as varicella, is a highly contagious disease caused by the initial infection with varicella zoster virus (VZV). The disease results in a characteristic skin rash that forms small, itchy blisters, which eventually scab ...

, and mumps. Common causes of bone and joint pain in adults, such as

and gouty arthritis are rare in children, as these diseases are a sequelae of chronic wear and tear for several years.

Cancer

Pain caused by cancer within bones is one of the most severe forms of pain. Because of its severity and uniqueness with respect to other forms of pain, it is extensively researched. According to studies of bone cancer in mouse

femur The femur (; ), or thigh bone, is the proximal bone of the hindlimb in tetrapod vertebrates. The head of the femur articulates with the acetabulum in the pelvic bone forming the hip joint, while the distal part of the femur articulates with ...

models, it has been determined that bone pain related to cancer occurs as a result of destruction of bone tissue. Chemical changes that occur within the spinal cord as a result of bone destruction give further insight into the mechanism of bone pain. Metastatic cancer cells often establish themselves within the

skeleton A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...

. When the cancer cells have metastasized, the mechanical dynamics of the bone matrix become weaker as skeletal strength decreases. This leads to several other complications throughout the body, including pain, thus decreasing the patient's quality of life.von Moos, R. Strasser, F. Gillessen, S. Zaugg, K. (2008). Metastatic bone pain: treatment options with an emphasis on bisphosphonates. ''Supportive Care in Cancer''. 16(10): 1105-1115. Bone tumors are composed of a conglomeration of cell types, including cancer and immune system cells. Often, tumor cells secrete growth factors that activate receptors close to primary afferent neurons. Activation of these neural receptors is a contributing factor to pain sensation. Additionally, inflammatory lipids called

prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...

s, which are produced at high rates by cancer cells within tumors, activate nociceptors when they bind together.

Pathophysiology

Stimulation of specialized pain-sensitive nerve fibers ( nociceptors) that innervate bone tissue leads to the sensation of bone pain. Bone pain originates from both the periosteum and the bone marrow which relay nociceptive signals to the brain creating the sensation of pain. Bone tissue is innervated by both

myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...

ated (A beta and A delta fiber) and unmyelinated ( C fiber) sensory neurons. In combination, they can provide an initial burst of pain, initiated by the faster myelinated fibers, followed by a slower and longer-lasting dull pain initiated by unmyelinated fibers. Nociceptors responsible for bone pain can be activated via several mechanisms including deterioration of surrounding tissue, bone destruction, and physical stress which shears the bone, vascular, muscle, and nervous tissue.

Treatment

The use of anesthetics within the actual bone has been a common treatment for several years. This method provides a direct approach using

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

s to relieve pain sensations. Another commonly used method for treating bone pain is

radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...

, which can be safely administered in low doses. Radiotherapy utilizes radioactive isotopes and other atomic particles to damage the DNA in cells, thus leading to cell death. By targeting cancer tumors, radiotherapy can lead to decrease in tumor size and even tumor destruction.Mercadante, S. (1997). Malignant bone pain: Pathophysiology and treatment. ''Pain''. 69(1-2):1-18. A form of radiotherapy that is often used in cases of bone cancer is systemic radioisotope therapy, where the radioisotopes target sections of the bone specifically undergoing metastasis. In the case of bone fractures, surgical treatment is generally the most effective. Analgesics can be used in conjunction with surgery to help ease pain of damaged bone.

Research

Mouse and other animal models are being heavily used to determine the neuron tissue densities in bone and mechanisms for maintenance of bone pain. This information is pertinent to determining the biological and physiological components of pain in the bone. By creating a detailed map relating the types of nerves going through the different sections of bone, it is possible to pin-point locations in the bone that are at a higher risk of being susceptible to bone pain. Treatments focusing on biological components such as cannabinoid receptors are being tested for effectiveness. Through testing in mouse models, it has been shown that activation of the CB-1 receptor helps reduce reactions associated with acute pain, indicating that it alleviates bone pain. Thus, a new target for potential treatments is activation of the CB-1 receptor.Furuse, S. Kawamata, T. Yamamoto, J. Niiyama, Y. Omote, K. Watanabe, M. Namiki, A.(2009). Reduction of Bone Cancer Pain by Activation of Spinal Cannabinoid Receptor 1 and Its Expression in the Superficial Dorsal Horn of the Spinal Cord in a Murine Model of Bone Cancer Pain. ''Anesthesiology''. 111: 173–86. Modern research and techniques are attempting to provide longer-lasting and more effective methods of treating bone pain by developing and applying new physiological knowledge of nervous tissue within the bone. If thorough understanding of the intra-neuronal mechanisms relating to pain can be developed, then new and more effective treatment options can be created and tested. Thus, it is critical to fully understand the mechanism which dictates bone pain.

Names

Bone pain is also known by the following names:

References

{{DEFAULTSORT:Bone Pain Pain Skeletal system