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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.
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. Ischemic bone disease or osteonercrosis is one example of pathology that can cause bone pain in the jaws.
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.
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 prostaglandins, which are produced at high rates by cancer cells within tumors, activate nociceptors when they bind together.