PALM SPRINGS, CALIF.—Cancer pain researchers participating in a symposium at the 2015 American Pain Society Annual Scientific Meeting reported that the extent of persistent, severe (i.e., breakthrough) pain is largely determined by malignant cells and their effectiveness at penetrating nerve fibers.
 
Brian L. Schmidt, DDS, MD, PhD, symposium speaker and a professor at New York University College of Dentistry and School of Medicine said cancerous cells are now known to “produce mediators that recruit and affect other cells within the cancer microenvironment, including nerves and immune cells. We now recognize that cancers and neurons act reciprocally on each other.”
 
But it is the malignant cell’s adeptness at neuroinvasion—when cancerous cells attack the body along nerves—that has been linked to more severe pain, aggressive pathologies and faster disease progression, and poorer prognosis. 
 
“The nerve itself is a key facilitator of adverse cancer cell behavior,” said Brian M. Davis, symposium chair and professor of neurobiology and medicine, University of Pittsburgh School of Medicine. “Tumors express nerve growth factor receptors and their ligands, both of which can interact with sensory fibers to cause sensitization and pain. Once the tumor cell is in the nerve, it can divide and grow, directly causing nerve damage and inciting neuropathic pain.”
Complicating the matter, according to Dr. Davis, is that once cancer cells are entrenched in the nerves, they are difficult to remove, even with chemotherapy drugs. 
 
Neuroinvasion is seen more often in specific cancer types, thus explaining in part why cancer pain—estimated at about 50% in all cancers—is particularly troublesome in certain types, such as bone cancer. “Many types of cancer frequently metastasize to multiple bones where they can cause significant, life-altering pain,” said Patrick Mantyh, PhD, symposium speaker and professor of pharmacology, University of Arizona, in Tucson. “Once cancer cells have metastasized to bones, they generate pain by directly injuring nerve fibers and inducing sensitization and activation of sensory and sympathetic nerve fibers that innervate the bone.”
 
Dr. Davis said nerves also play a large role in the progression of malignancies, pointing out that research now shows that tumors grow after interacting with nerves. “Sensory neurons release molecules that either negatively alter the tumor microenvironment to promote tumorigenesis or directly interact with cancer stem cells to accelerate the disease,” Dr. Davis noted.
 
Dr. Schmidt said a thorough understanding of the causes of cancer pain will allow researchers to develop effective treatments, adding, “Future research might conclude that pharmacologic and nonpharmacologic antagonism of mechanisms in the neurosensory system and mechanisms integral to cancer proliferation are required to achieve improved relief of cancer pain.”  
—PMN Staff
Based on a press release from the American Pain Society.