Mechanisms and management of bone cancer pain

Two main types of cancer pain exist: ongoing pain and incident or breakthrough pain. Ongoing pain is typically described as a dull and aching pain that is constant in nature and progresses in accordance with the disease process. Incident or breakthrough pain is most commonly associated with bone metastases and is characterized by sharp pains that are intermittent in nature and exacerbated by both volitional and non-volitional movements. Pain generally occurs during tissue ischemia and/or damage and is a result of release of neurotransmitters, cytokines and factors from damaged cells, adjacent blood vessels and nerve terminals. Pain is transduced at the level of the primary afferent nerve fiber which innervates peripheral tissues including bone. Recently, it has been shown that bone is densely innervated by both sensory and sympathetic nerve fibers within bone marrow, mineralized bone and periosteum. Sensory and sympathetic neurons are present within all three anatomic locations and are influenced by fractures, ischemia or the presence of tumor cells and may play a unique but coordinated role in the generation of bone cancer pain. Pain research has significantly improved our understanding of acute and chronic pain mechanisms. By highlighting key molecular mechanisms involved in pain transmission, new drugs are currently being investigated as potential novel and selective therapies. Currently available medications such as the opioids are certainly fraught with side effect profiles that may limit their clinical efficacy and patient quality of life. Research is now focused on specific receptor or channel targets within the nervous system that limits systemic complications.