Bone pain in cancer patients — what is known about its pathomechanisms?

Abstract

Bone is after lung and liver the third most common site of metastatic disease in cancer patients. Many cancer types including breast, prostate, lung, and kidney have a strong predilection to metastasize to bones, which induce pain, pathologic skeletal fractures, spinal instability and compression of the spinal cord or others structures of nervous system, hypercalcemia, decreased mobility and increased mortality. Bone cancer pain is a kind of chronic pain with unique and complicated pathophysiology with both a nociceptive and neuropathic component. The nociceptive component of cancer bone pain is driven by the release of pronociceptive substances produced by tumor and their stromal cells, acidosis caused by bone-destroying osteoclasts, and mechanical destabilization and fracture of the bone. The neuropathic component of cancer bone pain is induced by tumor cell growth which injures and destroys structures of nervous system and distal ends of nerve fibers that normally innervate the bone, by release factors that sensitize and activate bone nociceptors, and release growth factors that drive pathological ectopic sprouting of both sensory and sympathetic nerve fibers and neuroma formation. These newly sprouted nerve fibers which can be observed in the periosteum, mineralized bone, and marrow have a unique morphology, organization, and a high density that is never observed in normal bone. All described mechanisms contribute to peripheral and central sensitization observed in cancer patient with bone metastases.