Bone pain
Encyclopedia
Bone pain is a debilitating form of pain
emanating from the bone
tissue. It occurs as a result of a wide range of diseases and/or physical conditions and may severely impair the quality of life for patients who suffer from it. Bone pain has multiple causes, such as extensive physical stress and diseases such as cancer
.
For many years, it has been known that bones are innervated with sensory neurons. Yet, their exact anatomy remained obscure due to the contrasting physical properties of bone and neural tissue. However, until recently, it was not determined what types of nerves innervated which sections of bone. The periosteal layer of bone tissue, is highly pain sensitive, and an important cause of pain in several disease conditions causing bone pain, like fractures, osteoarthritis, etc. However, in certain diseases the endosteal and haversian nerve supply seems to play an important role, e.g. osteomalacia, osteonecrosis, and so on. Thus, there are several types of bone pain, each with many potential sources or origins of cause.
, Paget’s disease
, sickle cell anemia
, and bone cancer
.
From a health-care perspective, it is important to know what malady affects the patient so that the appropriate treatment can be administered.
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.
Metastatic cancer cells often aim to establish themselves within the skeleton
. 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.
Bone tumors are composed of a conglomeration of cell types including cancer and immune system cells. Oftentimes tumor cells secrete growth factors which activate receptors close to primary afferent neurons. Activation of these neural receptors is a contributing factor to pain sensation. Additionally, inflammatory lipids called prostaglandin
s, which are produced at high rates by cancer cells within tumors, activate nociceptors when they bind together.
Common causes of bone and joint pain in adults, such as osteoarthritis
and gouty arthritis are rare in children, as these diseases are a sequelae of chronic wear and tear for several years.
s to relieve pain sensations.
Another commonly used method for treating bone pain is radiotherapy
, 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. 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.
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
.
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.
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
emanating from the bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
tissue. It occurs as a result of a wide range of diseases and/or physical conditions and may severely impair the quality of life for patients who suffer from it. Bone pain has multiple causes, such as extensive physical stress and diseases such as cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
.
For many years, it has been known that bones are innervated with sensory neurons. Yet, their exact anatomy remained obscure due to the contrasting physical properties of bone and neural tissue. However, until recently, it was not determined what types of nerves innervated which sections of bone. The periosteal layer of bone tissue, is highly pain sensitive, and an important cause of pain in several disease conditions causing bone pain, like fractures, osteoarthritis, etc. However, in certain diseases the endosteal and haversian nerve supply seems to play an important role, e.g. osteomalacia, osteonecrosis, and so on. Thus, there are several types of bone pain, each with many potential sources or origins of cause.
Causes
A number of diseases may cause bone pain including osteoarthritisOsteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
, Paget’s disease
Paget's disease of bone
Paget's disease is a chronic disorder that can result in enlarged and misshapen bones. The excessive breakdown and formation of bone tissue causes affected bone to weaken, resulting in pain, misshapen bones, fractures, and arthritis in the joints near the affected bones...
, sickle cell anemia
Sickle-cell disease
Sickle-cell disease , or sickle-cell anaemia or drepanocytosis, is an autosomal recessive genetic blood disorder with overdominance, characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various...
, and bone cancer
Bone tumor
A bone tumor refers to a neoplastic growth of tissue in bone. Abnormal growths found in the bone can be either benign or malignant .-Classification:...
.
From a health-care perspective, it is important to know what malady affects the patient so that the appropriate treatment can be administered.
Pathophysiology
The stimulation of the 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 myelinated and unmyelinated sensory neurons (A-β, A-δ and C fibers). In combination, they can provide an initial burst of pain (myelinated neurons) followed by a slower and longer lasting dull pain (unmyelinated neurons).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.
Bone Cancer
Bone cancer is one of the most serious 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 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 aim to establish themselves within the skeleton
Skeleton
The skeleton is the body part that forms the supporting structure of an organism. There are two different skeletal types: the exoskeleton, which is the stable outer shell of an organism, and the endoskeleton, which forms the support structure inside the body.In a figurative sense, skeleton can...
. 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.
Bone tumors are composed of a conglomeration of cell types including cancer and immune system cells. Oftentimes tumor cells secrete growth factors which activate receptors close to primary afferent neurons. Activation of these neural receptors is a contributing factor to pain sensation. Additionally, inflammatory lipids called prostaglandin
Prostaglandin
A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....
s, which are produced at high rates by cancer cells within tumors, activate nociceptors when they bind together.
Causes
- Acute leukemiaAcute leukemiaAcute leukemia or acute leukaemia is a generic term used to describe a family of serious medical conditions relating to an original diagnosis of leukemia...
- Acute rheumatic fever, a very dangerous disease that can cause permanent cardiac damage.
- BursitisBursitisBursitis is the inflammation of one or more bursae of synovial fluid in the body. The bursae rest at the points where internal functionaries, such as muscles and tendons, slide across bone. Healthy bursae create a smooth, almost frictionless functional gliding surface making normal movement painless...
- FibromyalgiaFibromyalgiaFibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...
like disease has been studied as a cause of joint pain in the child. - Hypermobility syndrome can present with knee or ankle pain
- InjuryInjury-By cause:*Traumatic injury, a body wound or shock produced by sudden physical injury, as from violence or accident*Other injuries from external physical causes, such as radiation injury, burn injury or frostbite*Injury from infection...
such as a fractureFractureA fracture is the separation of an object or material into two, or more, pieces under the action of stress.The word fracture is often applied to bones of living creatures , or to crystals or crystalline materials, such as gemstones or metal... - Juvenile rheumatoid arthritis
- LupusLupusLupus most commonly refers to the disease systemic lupus erythematosus.Lupus may also refer to:-Medicine:* Lupus erythematosus, a chronic autoimmune disease with several different forms...
- Lyme diseaseLyme diseaseLyme disease, or Lyme borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Borrelia burgdorferi sensu stricto is the main cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii cause most...
, which is transmitted by ticks and is characterized by debilatating polyarthritis, neurologic symptoms, and erythema migrans. - OsteomyelitisOsteomyelitisOsteomyelitis simply means an infection of the bone or bone marrow...
- OsteosarcomaOsteosarcomaOsteosarcoma is an aggressive cancerous neoplasm arising from primitive transformed cells of mesenchymal origin that exhibit osteoblastic differentiation and produce malignant osteoid...
- Septic arthritisSeptic arthritisSeptic arthritis is the purulent invasion of a joint by an infectious agent which produces arthritis. People with artificial joints are more at risk than the general population but have slightly different symptoms, are infected with different organisms and require different treatment. Septic...
, a severe infection of the joint that can lead to permanent joint damage. - SynovitisSynovitisSynovitis is the medical term for inflammation of the synovial membrane. This membrane lines joints which possess cavities, known as synovial joints. The condition is usually painful, particularly when the joint is moved. The joint usually swells due to synovial fluid collection.Synovitis may...
- ViralVirusA virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
diseases, including the measlesMeaslesMeasles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...
, influenzaInfluenzaInfluenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
, mononucleosisMononucleosisMononucleosis , is a disease most commonly caused by the Epstein-Barr virus . The EBV virus affects the lymphocytes- white blood cells that battle infections by attacking antibodies. Mononucleosis can also be caused by Cytomegalovirus , a herpes virus most commonly found in body fluids...
, chickenpoxChickenpoxChickenpox or chicken pox is a highly contagious illness caused by primary infection with varicella zoster virus . It usually starts with vesicular skin rash mainly on the body and head rather than at the periphery and becomes itchy, raw pockmarks, which mostly heal without scarring...
, and mumps.
Common causes of bone and joint pain in adults, such as osteoarthritis
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
and gouty arthritis are rare in children, as these diseases are a sequelae of chronic wear and tear for several years.
Treatment
The use of anesthetics within the actual bone has been a common treatment for several years. This method provides a direct approach using analgesicAnalgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
s to relieve pain sensations.
Another commonly used method for treating bone pain is radiotherapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
, 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. 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.
Scientific Research and Future Treatments
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
Cannabinoid receptor type 1
The cannabinoid receptor type 1, often abbreviated to CB1, is a G protein-coupled cannabinoid receptor located in the brain. It is activated by endocannabinoid neurotransmitters including anandamide and by the compound THC, found in the psychoactive drug cannabis.-Expression:The CB1 receptor is...
.
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.