Cancer and pain often go together. Cancer starts slowly, but as tumours grow and press on bones or nerve endings, tumours become painful, and pain often becomes the most debilitating, and feared, aspect of the disease.
But it’s not just the physical pressure of tumours that causes pain. Tumours also cause changes in the tissues around and can lead to interactions between our immune and nervous system, resulting in pain both at the site of the tumour and elsewhere in the body.
The neuro-immune interactions with cancer are still not well understood, but research is beginning to give us new insights into how these signals affect our bodies, and how we can manage them to control cancer pain.
A review by clinician scientists Dr Matthew Brown, a pain research fellow at the Royal Marsden Hospital and a research student here at The Institute of Cancer Research in London, and Dr Juan Ramirez from the University of Oxford, has looked at previous research into cancer pain, and finds there are several distinct mechanisms at play – occurring before, during and after treatment.
Tumours are not only made up of malignant cells, but also a host of immune cells and others that make up the structural tissue around it. Tumours and their surrounding tissue are constantly interacting, sending signalling molecules back and forth that attract more cells to the site of the tumour. This ‘cross-talk’ also alters the tumour’s local environment to help it grow and invade new tissue.
Nerves growing at the site of the tumour that sense pain get confused and muddled up with nerves which detect other senses like touch, like switching around cables in a telephone junction box, causing inappropriate pain signals to the brain.
Tumours and the surrounding cells also release chemicals like TNFα and hydrogen ions resulting from tumour hypoxia, which stimulate nerve cells to cause pain. Other signalling molecules are released which encourage nerve growth and sensitise fibres to pain signals, further amplifying the pain caused by tumours.
Cancer treatment can also lead to pain. In surgery, a slew of compounds that cause pain and inflammation are released by the body to help the wound healing process. Normally these go away over time, but in some patients the pain doesn’t stop, leading to a condition called chronic or persistent pain.
Damage to sensory fibres combined with inflammation from surgery can sensitise nerves in the spinal cord and brain, causing heightened perception of pain in the patient. Surgery can also cause changes in gene expression of nerve fibres that increase communication between nerve cells. These can lead to increased pain sensitivity, and even pain from the slightest touch.
For some types of cancer surgery, the rate of chronic pain can be greater than 50%, which can seriously affect a patient’s quality of life after treatment and be difficult and expensive to manage.
Other types of pain can limit how much of certain cancer treatments a patient can receive, or whether experimental treatments are deemed safe to use clinically.
Chemotherapy-induced peripheral neuropathy is a major side-effect of chemotherapy and current ways to manage the pain are not terribly effective. Studying why chemotherapy drugs cause pain in some patients more than others might help doctors to improve treatment plans, and could even be used to re-assess drugs that had previously failed in clinical trials.
Of course, as scientists discover new treatments for cancer, new forms of cancer pain will arise. But as our understanding improves of how tumour cells and how our body’s immune and nervous systems interact, we should get better at managing cancer pain.
Like a training regimen for a high-performance athlete, the way that pain is treated for patients with cancer needs to be highly specialised. Making treatments more tolerable for each patient would not only benefit them in the short-term – it could also lead to better treatment outcomes more generally and less pain long term.
Understanding how and why cancer causes pain could even help researchers to develop new types of treatment that cause less painful side-effects in the first place.
Gradually we are moving towards new cancer treatments that cause less pain but more gain.
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