Study seeks to tackle pain in adult survivors of childhood cancer

A team at Nottingham Trent University is uncovering the biological pathways through which chemotherapy, a treatment used to kill cancer cells, can cause patients to experience chronic pain conditions – often in the hands and feet – when they are free of cancer.

The Nottingham researchers have previously found that exposure to chemotherapy in early life can damage nerve cells in the body that detect pain, altering how pain is perceived as a patient grows into adulthood.

It is known that the body mounts an inflammatory response to toxic agents such as chemotherapy through the activation of white blood cells, which is the body’s immune system.

These immune cells try to help and support damaged tissues and organs, including nerves, that have been damaged by chemotherapy, but in doing so can often facilitate damage as the immune cells themselves are also disrupted and activated by chemotherapy agents.

The Nottingham group believes white blood cells transfer ‘mitochondria’ – which provides cells with energy – to chemotherapy damaged nerves, helping to rescue the cell’s function and prevent pain.

If these white blood cells are also treated with the same chemotherapeutic agent, however, they will transfer considerably less mitochondria to nerve cells, causing a change in how the nerves perceive pain.

The new two-year study, being funded by the Medical Research Foundation, will involve initial work in mice to investigate the potential for transferring healthy mitochondria to protect nerves from causing pain.

From this study the team aims to identify potential avenues to design new painkillers that rescue nerve function and alleviate pain in individuals that have undergone childhood cancer treatment.

Thanks to significant advances in detection and treatment regimes, there is now an 80% survival rate for childhood cancers, but the long-term effects of treatment can be felt for many years, with more than half of childhood cancer survivors reporting chronic and progressively painful symptoms in their hands and feet.

The researchers argue that the pain caused by chemotherapy is poorly-managed by current anti-inflammatory and analgesic medicines, largely due to the lack of understanding of how chemotherapy causes changes in peripheral nerves associated with pain recognition.

“There has been a significant improvement in lifespan post cancer treatment, and while amazing, this has brought to light other medical challenges,” said Dr Richard Hulse, a scientist who specialises in sensory physiology in Nottingham Trent University’s School of Science and Technology.

He said: “Ongoing pain post-treatment is a significant problem in children that live into adulthood and can severely impact their quality of life, but we still know little about the biological pathways and mechanisms driving this.

“In normal cases, the body’s natural immune system would help preserve the mitochondria of nerve cells that detect pain – however, chemotherapy stops this from happening. We want to explore how the immune system and these nerve cells interact.

“Mitochondria are important as they provide the cells with energy. So, if functional healthy mitochondria are transferred this may help nerve health. We believe this could provide a unique pathway to protect nerves from pain and provide an avenue to identify potential new treatments.”