It is estimated that 60% to 84% of cancer patients develop bone metastases. Of these, 70% experience a pain syndrome that is difficult to manage, of which 50% die without adequate pain relief with poor quality of life. Therefore, it is necessary to have accessible and effective medicines for the management of this condition. It is difficult to manage and control in clinical practice. Today, scientific advances in cancer detection and treatment have lengthened the life expectancy of patients. Unlike the case of bone pain occurrence in cancer, where current treatment strategies are not quite effective. Most palliative treatments for bone pain are based on experimental studies on pain management in patients or on experimental models that are not well designed, which may explain why the drugs used are partially effective. Today, one of the main obstacles to the development of new and safe treatments to control bone pain is the absence of basic scientific knowledge in the physiology of bone pain.
Physiology of bone pain
Generally, osteoclastic bone regeneration is in equilibrium with osteoblast-mediated bone formation. In neoplastics, osteolytic activity increases and contains substances such as cytokines, local growth factors, peptides similar to parathyroid hormones, and prostaglandins. Autocids are also released from other owners such as potassium ion, bradykinin, and osteoclast activating factors. These tissue substances play an important role in sensitizing neural tissue to chemical and thermal stimuli, lowering neuronal membrane discharge thresholds, causing exaggerated responses to above-threshold stimuli, and in general silent nociceptor tonic impurities. Discharge results. This phenomenon is called peripheral sensitization and primary overgrowth and is understood as events that occur within rows of injured tissue and stimulate peripheral nociceptors (C fibers and delta A fibers) that translate to pain. . In bone tissue, sensory receptors are mainly found in the periosteum, whereas bone marrow and bone cortex are insensitive. This phenomenon of peripheral sensitization results in abnormal sensitivity to pressure around the skin (allodynia and hyperlegia), exposure to bone, muscles, tendons, joints, and deep tissues. It is limited to ensuring that the peripheral ends are more responsive to injury alarms.
The continued presence of noxious processes, stimulating nociceptive receptors, introduces a subacute pain that becomes chronic with the development of bone metastases. These stimuli lead to another prevalent phenomenon called major central sensitization that involves abnormal amplification of the sensory signals coming to the central nervous system, particularly the spinal cord. The phenomenon occurs due to continuous input stimulation through the C fiber. This triggers a temporary increase in the strength of the spinal silent synaptic terminals. The glutamate N-methyl-D-aspirate (NMDA) receptor plays an important role in this process. Amplification as a result of the signal generated in the postsynaptic neuron sends a message to the brain that is interpreted as pain. In summary, central sensitization enhances the sensory effects of both peripheral nociceptive input (C pain fibers) and non-nociceptive fibers (A of touch).
In practice, the two events are altered in the genesis of metastatic bone pain and peripheral sensitization occurs to reveal nasaticeptors and the translation of information transmitted through myelinated afferent or C-cullinated A-delta fibers to the spinal cord. Does in Where the information is. Modified by various systems. With the subacute start-up process, the central sensitization process begins, with sensory synapses activated.