What causes Chronic Fatigue Syndrome?

When it comes to controversy and heated debate, few illnesses come close to Chronic Fatigue Syndrome, also known as Myalgic Encephalomyelitis (ME).

There have been arguments about whether it exists, the cause, the best treatments and even the name itself.

These disagreements have reached the level of abuse and death threats.

The disease itself, however, remains poorly understood - or as one doctor put it: "The whole thing is surrounded by uncertainty".

Does it exist?

For a long time, the existence of CFS/ME was widely dismissed and labelled as "yuppie flu". That opinion has largely been reversed in the past decade.

Continue reading the main storyToo vague, too precise?

Should the illness be called CFS, ME or CFS/ME?

Doctors prefer the term CFS as the main symptom is fatigue, while ME has a specific meaning related to inflammation of the brain and spinal cord.

However, this is not popular with some patients' groups or charities, which talk about ME as a specific disease, saying "fatigue" is too broad a term.

Prof Michael Sharpe, of the University of Oxford, said: "The concepts of CFS and ME have been conflated as CFS/ME. That may be right but it may be a bit like an apple/banana - we need to be clearer what we are talking about."

In 2002, then chief medical officer Prof Sir Liam Donaldson described it as a "disease in the wilderness". He was presenting a report which said CFS/ME was a "genuine illness and imposes a substantial burden on the health of the UK population".

It is thought to affect about a quarter of a million people in the UK.

The main symptom is severe fatigue, made worse by exertion, which does not go away after resting. Muscle pains, headaches, memory problems and depression can also be involved. In some cases it can be completely debilitating, resulting in patients being unable to leave their beds.

Understanding of the disease is largely led by those symptoms. There is no test for CFS/ME, instead it is diagnosed by ruling out other conditions which might produce the same symptoms.

The underlying cause, or indeed causes, have been more elusive.

Uncertain origins

One of the issues in the field is that there is an emerging consensus that CFS/ME is not one illness.

Gene find 'may curb chronic pain'

Lower back pain can be a chronic, lifelong condition for many people Hope over NHS pain relief implant A gene responsible for chronic pain has been identified, with scientists saying this could lead to drugs for treating long-lasting back pain.

Writing in the journal Science, University of Cambridge researchers removed the HCN2 gene from pain-sensitive nerves in mice.

Deleting the gene stopped any chronic pain but did not affect acute pain.

About one in seven people in the UK suffer from chronic pain, which can also include arthritis and headaches.

The researchers say their findings open up the possibility that new drugs could be developed to block the protein produced by the HCN2 gene, which regulates chronic pain.

The HCN2 gene, which is expressed in pain-sensitive nerve endings, has been known for several years, but its role in regulating pain was not understood.

For the study, the researchers removed the HCN2 gene from pain-sensitive nerves. They then carried out studies using electrical stimuli on these nerves in cell cultures to determine how they were altered by the removal of HCN2.

Continue reading the main story“Start QuoteIndividuals suffering from neuropathic pain often have little or no respite because of the lack of effective medications”

End QuoteProf Peter McNaughtonUniversity of Cambridge They then studied genetically modified mice in which the HCN2 gene had been deleted.

By measuring the speed that the mice withdrew from different types of painful stimuli, the scientists were able to conclude that deleting the HCN2 gene abolished neuropathic pain.

However, they found that deleting HCN2 did not affect normal acute pain - which occurs suddenly, for example when biting one's tongue.

'No respite'

Chronic pain comes in two main varieties. Inflammatory pain occurs when a persistent injury, such as a burn or arthritis, results in very sensitive nerve endings which increase the sensation of pain.

Neuropathic pain occurs when nerves are damaged, causing ongoing pain. This type of chronic pain, which is often lifelong, is surprisingly common and is poorly treated by current drugs, the study says.

It is often seen in patients with diabetes and shingles, and in the aftermath of cancer chemotherapy. It is also common in lower back pain and other chronic painful conditions.

Professor Peter McNaughton, lead author of the study and head of the department of pharmacology at the University of Cambridge, said there was now hope for these people.

"Individuals suffering from neuropathic pain often have little or no respite because of the lack of effective medications. Our research lays the groundwork for the development of new drugs to treat chronic pain by blocking HCN2."

He added: "Many genes play a critical role in pain sensation, but in most cases interfering with them simply abolishes all pain, or even all sensation.

"What is exciting about the work on the HCN2 gene is that removing it - or blocking it pharmacologically - eliminates neuropathic pain without affecting normal acute pain. This finding could be very valuable clinically because normal pain sensation is essential for avoiding accidental damage."

Dr Brian Hammond, chairman of charity BackCare, said the findings of the study were good news.

"Any effective treatment which relieves the suffering of chronic pain is to be welcomed. Treatment which helps reduce pain but still leaves the body's warning mechanisms intact is a major breakthrough."

The study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), and the European Union.