Molecular mechanisms of cancer pain

As advances in cancer detection and therapy are extending the life expectancy of cancer patients, there is increasing focus on improving the quality of life of patients. New approaches are desperately needed to control cancer-associated pain. Sensory information from peripheral tissues is transmitted to the spinal cord and brain by primary afferent sensory neurons. Specialized sensory neurons — known as nociceptors — detect and convert environmental stimuli that are perceived as harmful into electrochemical signals that are transmitted to the central nervous system. Tumours secrete a variety of factors that sensitize or directly excite primary afferent neurons, causing the sensation of pain. Receptors for many of these factors are expressed by primary afferent neurons. Both the intracellular and extracellular pH of solid tumours are lower than that of surrounding normal tissues, which can also activate sensory neurons and cause pain in cancer patients. Tumour growth entraps and injures nerves, causing neuropathic pain. The spinal cord and forebrain undergo neurochemical and structural changes as a state of chronic pain develops. Cancer pain frequently becomes more severe as the disease progresses, and might require different types of analgesic at different time points. For the first time, animal models of cancer pain are now available. These will offer insight into one of the main conundrums of cancer pain — why the severity of this pain is so variable from patient to patient, tumour to tumour, and even from site to site.