Illness link to stress in childhood

RESEARCHERS IN Cork have established a direct link between early childhood stress and the development in later life of Irritable Bowel Syndrome (IBS). They also believe they know why the condition occurs and have a novel new treatment for it, writes DICK AHLSTROMScience Editor

IBS is the most common disorder to prompt a visit to a gastroenterologist.

It can be debilitating, causing severe abdominal or “visceral” pain, but when doctors look they can find no obvious cause.

Dr John Cryan and Prof Ted Dinan at University College Cork (UCC) decided to follow up on clinical findings that IBS patients often seemed to report stress as a contributor to their condition.

“Patients who have IBS, which is characterised by visceral abdominal pain also have a lot of stress in their lives,” says Dr Cryan. Patients also often reported having experienced highly stressful events during childhood such as the death of a family relative or other significant trauma.

“This is much, much higher in the IBS population than in the normal population,” he says.

The two researchers, who run a neurogastroenterology group within the alimentary pharmabiotic centre at UCC, decided to study this to see whether there was a formal link between childhood stress and IBS.

“What we are doing is looking for biomarkers for the disorder,” says Cryan, who is based in the school of pharmacy and in the department of pharmacology and therapeutics at UCC.

Given IBS is associated with severe pain, they decided to look for biochemical markers in the spinal cord. Nerve tissue carries the pain signals but the main connections along the spine are also involved.

“The spinal cord is very important in controlling pain signalling,” he says.

Their study, which involved using a rat model for IBS, is published this morning in the prestigious journal Gastroenterology. They revealed that patients with IBS had low levels of an essential protein.

“We found there was a decrease in a specific protein called the ‘glutamate transporter’ in their spinal cords,” he says.

Glutamate is a neurotransmitter, a substance that allows signals to travel between nerve cells.

Having too much glutamate in the nerve cells however, can trigger pain and the glutamate transporter is produced to mop up glutamate and take it back out of the nerve cells.

The researchers found the IBS rats produced too little glutamate transporter and as a result their spinal glutamate levels went up.

They believe that the higher glutamate levels contribute to the experience of abdominal pain seen in IBS patients.

If this is true, then reducing glutamate levels should also reduce pain, Cryan says.

They tested this by giving a drug used in the treatment of motor neuron disease, riluzole, which helps glutamate transporter reduce glutamate levels. Once given, glutamate levels fell and so did the pain associated with IBS, Cryan says.

The finding is important on a number of levels. It provides an explanation for the pain associated with IBS and also a way to reduce this with an existing drug.

But it also suggests an initial trigger for IBS – stress – particularly in early childhood. “We do know that stress will alter glutamate levels,” Cryan says. “That is one of the things that is causing [IBS symptoms].”

The focus now is to understand what changes take place in the brain and nervous system as a result of childhood stress to make IBS occur in later life, he says.

Parallel to this is the need for better drugs to help the glutamate transporter do its job.

“Riluzole is extremely expensive and only used in that disorder. Patients need a drug that targets the glutamate transporter specifically,” Cryan says.

The work also provides a reason why the conventional pain-killers given to IBS patients are not very effective. “The glutamate seems to be quite specific to IBS pain and not other sources of pain. This is one of the big problems with the disease,” he says.

“There is something special about visceral pain and unlocking how that happens is one of our big aims in the study.”

The gastroenterology paper was co-authored by UCC researchers Dr Romain-Daniel Gosselin, Richard O’Connor, Dr Monica Tramullas and Dr Marcela Julio-Pieper