Nerve Growth Factor Causes Cancer Pain

Sensory nerve fibers surrounding tumors undergo pathological remodeling and growth that generates and amplifies cancer pain.

Cancer patients are living longer than ever before. But pain associated with cancer remains the most feared aspect of the disease and can be highly debilitating for the patient.

New discoveries in the field of cancer pain at the University of Arizona have provided revealing insights into what drives cancer pain, and scientists have identified a therapy to more effectively manage the pain.

The research was published in the Journal of Neuroscience and focuses on prostate cancer-induced pain. Prostate cancer cells avidly metastasize to the bone and cause an “ongoing” pain that is characterized as a dull and aching. It later can become a more severe "breakthrough" pain that can be difficult to fully control, according to a press release.

Breakthrough pain is pain that "breaks through" the therapies the patient is given to treat the ongoing pain. This type of pain is difficult to control as it can occur several times a day, is more severe than ongoing pain, its onset is unpredictable and rapid (seconds to minutes), and it can occur either spontaneously or from movement of the tumor-bearing organ.

“When breakthrough pain is not fully controlled, the patient's quality of life significantly decreases as does his or her functional status,” said Patrick Mantyh, a UA neurobiologist and professor in the department of pharmacology in the UA College of Medicine and lead study author, in a press release.

He and his team began the study by asking, what mechanisms drive cancer pain, do these mechanisms change with disease progression, and can we use this increased understanding to develop new therapies to control this pain?

The findings, which were funded by the Veterans Administration and the NIH, surprised the researchers with results that no one in the field had anticipated.

The team discovered that sensory nerve fibers that innervate the tumor-bearing tissue undergo a dramatic remodeling. The nerve fibers undergo a pathological sprouting and reorganization, which in other nonmalignant pathologies has been shown to generate and maintain severe and difficult-to-control chronic states of pain.

"We came into the research thinking nerves that innervate the tumor-bearing organ were static structures," Mantyh said.

Instead, they found that as the cancer invades an organ, the sensory nerve fibers that innervate the organ undergo a remarkable and pathological remodeling and growth that generates and amplifies cancer pain.

“We have never observed this level of pathological reorganization and growth of the sensory nerve fibers in other normal non-cancerous pain states. We believe that these pathological changes set in place and anatomical substrate that greatly contributes to both ongoing and breakthrough cancer pain,” Mantyh said, who holds a joint appointment at the Arizona Cancer Center and the Veterans Affairs Medical Center in Minnesota.

The study also identified a therapy that not only reduced the pathological reorganization but alleviated the cancer pain.

The main culprit in driving the pathological reorganization appears to be a nerve growth factor. The researchers found that a preventive treatment with an antibody can sequester the nerve growth factor, blocking the ectopic sprouting resulting in attenuated cancer pain.

“This research has the potential to dramatically change the way we understand and treat cancer pain,” Mantyh said.

According to the researcher, just as cancer treatments are initiated early to battle the disease, this study suggests that the earlier therapies are initiated to block the pathological reorganization and sprouting of nerves, the better control clinicians will have in addressing cancer pain.

“Mechanism-based cancer therapies have dramatically improved our ability to treat cancer. In this study, we identified novel, mechanism-based therapy to control cancer pain that may allow the cancer patient/survivor to better maintain their quality of life, functional status and ability to fully enjoy life,” Mantyh said.

Source: University of Arizona


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