Pain in the CancerBone


 

Neurobiology investigations are leading to the development of new bone pain therapies that may help fight cancers.

Using neurobiology to derive models of bone cancer pain helps to identify the biological mechanisms that drive the bone pain. The aim is to enable the development of new drugs not just for bone cancer, but for other types of cancer as well.

Tumour growth slows down in the bone, and this may be a way tumours evade targeted treatments. So finding the mechanisms involved in tumor-related bone pain will help tackle bone cancers, and provide clues of how to prevent metastasis or spread of other types of cancers as well.

Bone pain occurs in up to 84% of all major cancers. Bone is a common tissue of cancer spread, and primary bone cancer is rare, particularly breast cancer and prostate cancers.

Red cells are made in bone and a number of factors are present in bone that speed up and slow down cell growth. In bone, many cancer cells slow down their growth, and they do not divide as fast.  This has the benefit that it slows down cancer progression and may prolong survivals. However, it also may mean that the cancer evade treatments for this reason. So when the cancer eventually spreads through the bone, and then recurs it can become widespread in the body.

So how do cancers cause bone pain? Some cancers produce chemicals that weakens and cracks bone and this leads to pain. However other cancers can also produce chemicals that harden bone, which thus can lose its functional elasticity and this also leads to pain. Also as tumor cells grow, nerve endings also go into the bone and this can cause pain.

Pain in the bone can often be the first sign of cancer and in prostate cancer bone pain manifesting as low back pain may be the presenting sign.

The way that an individual type of cancer impacts on bone and causes pain is variable. For example, prostate cancer generally leads to abnormal bone growth, whereas breast cancer is more likely to cause more bone destruction.

Spread of cancer from the bone tends to be to multiple organs. Understanding the interactions between tumor and bone may help to identify potential targets for chemotherapeutic intervention to halt tumor growth.

If the vertebrae are riddled with tumour cells, treatment is very difficult and irradiating the whole body or half the body if often required. Many patients already have bone marrow suppression making this an not a viable treatment option.

Breakthrough cancer pain is one of the most difficult types of pains to manage. It is not tumour breaking through the bone, but pain is breaking through the analgesic regime that the patient is on to manage their pain. For patients it is a very difficult pain to deal with because it feels as if the bone is breaking. It is a key pain to  target to improve quality of life and functional status.

As pain increases, the patient quality of life deteriorates. Stepwise pain control involves going from a non-opiate adjuvant to mild opiates and then on to strong opiates plus a NSAID  depending on increasing pain severity.

Despite escalating medication  most patients experience some breakthrough pain or end-of-dose pain. Opiates are very useful drugs but have significant side-effects that are more prevalent in the elderly.

 The cancer affects the areas of mechanical stress where there is greatest bone destruction from the tumour. Growth factors embedded in the bone stimulate tumour cells and further destroy the bone.

One of the reasons it is so difficult to treat cancer pain is that there is simply not one type of pain and there may be combinations of tumorigenic, neuropathic and inflammatory pain. In tumorigenic pain, tumour cells are secreting factors which excite the sensory fibres that radiate to the bone and other parts of the body. Much of a tumour mass is composed of inflammatory cells that potentially cause pain. Neuropathic pain occurs as the tumour is driving through the tissue that it is invading and it causes nerves to sprout.

The pain experienced by many cancer patients is probably all three of these types occurring simultaneously. So a therapy is being given to treat neuropathic pain and at the same time the inflammatory or neuropathic pain, as there is probably multiple mechanisms driving the pain.

 

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