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How Tumors Cause Pain--by David van Alstine,M.D.

There are many ways that tumors can cause pain in the human body. Sometimes the pain is created directly by the tumor, such as when a tumor stretches or distorts normal tissues. At other times, the pain is caused indirectly by reactions to tumor-made chemicals, blockage of ducts from internal organs, bleeding into the tissues, collapse of bones, or other events. At times, the treatments used to fight the cancer can also lead to pain problems.
With all this talk about hurting, if you are newly diagnosed with cancer, it is important to realize that some tumors cause no pain at all, while others simply careate a mild discomfort. Many people ignore unusual lumps or growths for too long; they assume it cannot be serious since it does not hurt. The cells that make up a cancer are from a person's own body, so they may not trigger a reaction from the immune system or from pain sensors. The body simply assumes that they are normal cells doing normal things.
One of the more futuristic ways to fight cancer cells involves creating special proteins called monoclonal antibodies that will stick to the cancer cells and suddenly make them visible to the body's own tumor-fighting cells. The goal of this type of treatment is to uncover the "stealth" cells that have turned cancerous and make them show up on the immune "radar" system.
Even when parts of the tumor have migrated through the blood stream or the lymphatic system and generated new metastasis growths, these may not cause pain. A look at the bone scan of a patient with metastatic cancer will often show several places that have been invaded, but are not hurting. For most cancer patients, there does eventually come a point, however, when the tumor causes pain. This may be even before the tumor is diagnosed, or not until late in the progression of the disease. Understanding how the cancer causes pain helps make sense of the treatments used to fight both the cancer and the pain.
Inflammation
As discussed, the initial sensation of pain and the transmittion of the pain message to the brain are both chemical processes. At the edges of a tumor, cancer cells are invading normal tissue, damaging and destroying normal cells. These damaged cells release a few simple molecules, signaling surrounding cells and starting the inflammatory process. These molecules are modified by other cells to produce a large number of different compounds, resulting in a "cascade" of inflammatory chemicals. Some of these chemicals, like the prostaglandins are involved in causing pain.
It is important to understand several things about the inflammatory process as it relates to cancer and pain. The first is that these chemicals and reactions in the tissue are part of the normal mechanism the body uses to fight infection and to heal itself. Some of the molecules that are created attract infection-fighting cells to the area of damage; others make the blood more likely to clot, minimizing any bleeding into the tissues. Other cells attracted by these chemicals help clean up cellular debris, some may attack cancer cells, and still others create scar tissue to begin the repair process. Even the fact that inflammation causes pain is important, because pain warns us that something has gone wrong and motivates us to seek help.
There are times, however, when the whole cascade of inflammation, and repair doesn't happen the way it should, such as when cancer cells escape being detected by the immune system and go on to badly injure the body. At other times, the response to injury or infection is more aggressive than needed for the situation. This happens, for instances, when a person is allergic to grass pollen or cat hair. The misery of a hayfever attack is caused by the body attacking something that is harmless and releasing a number of cheminals that trigger sneezing, watery eyes, and a runny nose.
When cancer first begins, the problem is less one of overreaction and more one of lack of detection. The tumor cells can be masters at hiding from our immune system since they arise from our own tissue, but at some point they begin to injure and start an inflammatory reaction. As the cancer cells grow and spread, they trigger pain through the inflammatory response. Although the reaction causes the same swelling and changes in blood clotting that an infection does, there is little evidence that this inflammation helps to fight the cancer.
Pain Origigating from Different Tissues and Organs.
We have discussed broad categories of pain, such as visceral and somatic pain. We considered the general way cancer causes inflammation and pain in any tissue it invades. It is also helpful to look at cancer pain according to the specific organs and tissues being affected.
There are several common ways that cancer causes pain when it infiltrates certain organs and disturbs normal function. Certain pains are best discussed by the organ affected, such as bone pain or nerve pain. In these cases, the pain is very similar, no matter what mechanism causing the pain, such as compression, bleeding, lack of blood flow, and so on. In these cases, the mechanism determines the characteristics of the pain and how we should best treat it.
Bone Pain
Invasion of bone by cancer is, unfortunately, a common event. Although some types of tumor originate in the bone itself (like osteosarcoma; "osteo" meaning bone and "sarcoma" being a type of malignant tumor), more frequently the tumor originated somewhere else and then metastasized to the bone. Cancer of the breast, kidney, lung, and prostate are more like to invade bones than are other types of cancers. The bones most commonly invaded are the vertebrae (spine), pelvis, and the long bones of the arms or legs.
Once cancer cells reach a bone, they begin to multiply, destroying healthy bone tissue as they grow. Sometimes the body fights back, forming new bone at the site of a tumor, but bone destruction is the overwhelming rule. Bone invasion sometimes causes the most extreme pain experienced by cancer patients, while at other times it causes no pain at all. It is common for a person to complain of severe pain from an invaded rib, for example, but the same completely painless. To undersant the reason for this, we have to understand the anatomy of a bone.
The bones are made up of a dense mineral complex created by cells scattered within the mineral matrix. The mineral complex is the substance we usually think of as bone; the cells are few in number. The mineral matrix is continually remodeled by these cells, however, to help strengthen parts of the bone that are under stress. Most bones have a dense mineral matrix on the outside, with a central portion of lacy or spongy bone that contains spaces filled with fat and special blood cells. The spongy interior, called marrow, serves as the manufacturing site for new red blood cells, white blood cells, and platelets. The outer portion of bone is called the cortex. The dense cortex is the strong part of the bone that provides its main structure and support.
Overlying every bone is a tough, fibrous covering called the periosteum. The periosteum contains many nerve endings and is therefore the most sensitive portion of the bone. The cortex and marrow of the bone contain few nerve endings. When bone pain occurs the perisoteum is actually the source of most of the pain, with only a small contribution from nerves within the bone itself.
A tumor can spread to any bone in the body, but there is a tendency to spread into those bones closes to the tumor, called direct extension. The direct extension of the tumor often occurs with lung or breast cancer that spreads to the ribs, or with cancers of the month and throat that invade the jawbone. However, direct extension can happen with nearly any type of tumor in any location. Direct extension usually begins on the outside of the bone and erodes inward.
When a tumor invades only the central part of the bone there is usually little pain, since there are few nerve endings located in that area. Whenever the perosteum becomes irritated, however, significant pain will occur. The irritation and stretching of this capsule causes a constant, deep aching pain that stress on the bone may worsen, such as when standing or moving. Itis not surprising, then, that direct extension of the tumor to the bone, which irritates the periosteum immediately, is usually painful as soon as it begins. Metastatic tumors, which usually begin in the center of the bone, are usually not painful until the tumor has grown enough to stretch the periosteum.
in addition to causing pain by irritating and inflaming the bone and periosteum, a tumor can cause pain by fracturing the bone. As cancer cells erode more and more of the mineral matrix, the bone continually weakens and eventually may fracture after no more stress than simply standing up. This kind of broken bone is termed a pathologic fracture becuse it does not involve enough injury to break a normal bone; it only occurred because of the pathology of tumor invading the bone. For example, pathologic rib fractures may occur after simply coughing or sneezing, or a hip fracture may occur simply from being the first indication that cancer is even present.
Pathologic fractures are not only a major cause of direct bone pain but also can limit the patient from doing other activities that are important or pleasurable. The bone at the fracture site is extremely weakened by the tumor and will not heal easily or with normal strength. It is often neccessary to surgically place internal support rods inside the bone, or to place metal plates and scews to bridge over the damaged area.
When cancer involves the bones of the spine, there can be serious problems with both pain and function. Since the spine must bear weight any time a person is sitting, standing, or moving, tumor-generated bone pain tends to be more constant and more disabling when it involves the spine. Additionally, if the tumor invades into the canals that house the spinal cord and major nerves, if can compress vital nervous tissues or even invade the nerves themselves. This can cause neuropathic pain in the nerves that are compressed and even stop the nerve from functionaing, resulting in weakness or partial paralysis.
Like other bones, a vertebra can fracture if the tumor destroys too much of its bone tissue. A pathologic fracture of a vertebra can sometimes cause catastrophic damage to the spinal cord and nerves and may require major surgery if the spine becomes unstable. Fortunately, most pathologic spine fractures do not cause significant nerve injury, nor do they require surgical repair. Such fractures do cause severe back pain, however.