An estimated 60% to 84% of patients with cancer develop bone metastasis. Of these 70% experience pain syndrome which is difficult to manage, of which 50% die without adequate pain relief with a poor quality of life. It is therefore necessary to have accessible and effective medications for the management of this condition. One of the most common pain syndromes in patients with advanced cancer is bone metastasis. This is difficult to manage and control in clinical practice. Currently, scientific advances in cancer detection and treatment have prolonged life expectancy in patients. Unlike the case with the phenomenon of bone pain in cancer, where current treatment strategies are not significantly effective. Most palliative treatment of bone pain are based on clinical studies on pain management in patients or in experimental models is not well designed this could explain why the drugs used are partially effective. Today, one of the main obstacles in developing new, safe treatments to control bone pain is the absence of basic science knowledge in the physiology of bone pain.
The pain in cancer patients is usually multifactorial, may arise from the process itself, treatment side effects or both. For these reasons the approach and management of this symptom should be multidisciplinary. Pain syndrome occurs either by local proliferation or tumor invasion of a metastatic tumor from a distance. With metastatic bone pain often reflects the presence of a tumor in breast, thyroid, prostate, kidney, lung or adrenal.
Physiology of bone pain
Bone pain is associated with tissue destruction by osteoclast cells. Normally, osteoclastic bone resorption are in balance with bone formation mediated by osteoblasts. In neoplastic osteolytic activity is increased and there are substances such as cytokines, local growth factors, peptides similar to parathyroid hormone and prostaglandins. Autacoids are also released other owners as potassium ions, bradykinin and osteoclast activating factors. These tissue substances play an important role in sensitizing the neural tissue against chemical and thermal stimuli, lower thresholds for discharge of the neuronal membrane, produce exaggerated responses to stimuli above the threshold and result in discharges of tonic impulses normally silent nociceptors. This phenomenon is called peripheral sensitization and primary hyperalgesia and is understood as events occurring within the ranks of the injured tissue and stimulate peripheral nociceptors (C fibers and A delta fibers) translating pain. In bone tissue of the sensory receptors are located primarily in the periosteum, whereas the bone marrow and bone cortex are insensitive. This phenomenon of peripheral sensitization results in abnormal sensitivity to pressure surrounding skin (allodynia and hyperalgesia), pain in muscles, tendons, joints and deep tissues in contact with bone. This is limited to ensure that the peripheral ends have a greater capacity for alarm response to injury.
The constant presence of harmful process, stimulating nociceptive receptors gives the introduction of a subacute pain that tends to be chronic with the growth of bone metastases. These stimuli lead to another prevalent phenomenon called central sensitization important which includes abnormal amplification of incoming sensory signals to the central nervous system, particularly the spinal cord. The phenomenon occurs because of the persistent input stimulus through the fibers C. This spinal cord triggers a temporary increase in the power of silent synaptic terminals. In this process plays an important role of glutamate receptor N-methyl-D-aspartate (NMDA). The resulting amplification of the signal generated in the postsynaptic neuron sends a message to the brain which is interpreted as pain. In short central sensitization amplifies the sensory effects of both peripheral nociceptive inputs (C fibers of pain) and non-nociceptive fibers (A of touch).
In practice the two phenomena come together in the genesis of metastatic bone pain and peripheral sensitization occurs acutely metastatic lesions to appear nociceptors and translate the information conveyed through the afferent myelinated A-delta or unmyelinated C fibers to the spinal cord where the information is modulated by various systems. With the set up process subacute begins the process of central sensitization which sensory synapses begin to activate silent. And there is a state of increased central perception. By becoming chronic pain phenomenon becomes even more complex because all that is in contact with the area of injury becomes a powerful generator of pain. The touch, muscle movement or joint pain result, manifesting the phenomena of allodynia and hyperalgesia much more marked.
With progression and growth of metastatic disease can appear phenomena of compression of peripheral nerves, nerve roots or spinal cord. Then the pain can refer to other dermatomes, further complicating the initial picture painful. This condition becomes a debilitating factor for the patient and to be inadequately controlled could trigger the phenomenon of total pain detailed below.