Flinders University researchers at South Australian Health and Medical Research Institute have made an important discovery about the pain experienced in cases of irritable bowel syndrome (IBS).
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They have identified receptors in the nervous system that causes chronic pain, a finding that could lead to new ways of treating its underlying cause, says study author Stuart Brierley.
Patients with IBS suffer from chronic abdominal pain and experience rewiring of their nervous system so they feel pain when they shouldn't - we decided to ask important questions about how nerves in the gut are activated to cause pain in order to seek out potential solutions."
Stuart Brierley
IBS affects up to 15% of the world’s population
IBS is a gastrointestinal disorder characterized by pain and discomfort in the abdomen and changes in bowel habits, which may be recurrent diarrhea, constipation or both.
IBS is one of the most common gastrointestinal common disorders in the world, affecting between 25 and 45 million people in the United States and an estimated 10-15% of the population worldwide.
In the United States alone, there are between 2.4 and 3.5 million physician visits for IBS every year.
The condition can develop at any age, but usually, symptoms first start to emerge between the ages of 20 and 30 and it is unusual for people to first experience them after the age of 50.
The impact of IBS may range from mildly inconvenient to severely debilitating since it can influence many aspects of a person’s social, professional and emotional life.
The brain-gut connection
Research into IBS has shown that IBS is caused by underlying mechanisms within both the brain and the bowel. Certain physical factors such as increased sensitivity to pain in the bowel are linked to the central nervous system. Psychological and social aspects such as anxiety can also contribute to whether a person develops systems and how long they have them. Anxiety and stress do not cause IBS, but this gut-brain connection means these feelings can induce or worsen symptoms.
Receptors in skin also exist in the human gut
Now Flinders University researchers have made the interesting discovery that the same receptors in the skin that cause it to itch also exist in the human intestine, where they activate neurons. This results in patients with IBS feeling chronic gut pain or what could be referred to as a “gut itch.”
"We found receptors which bring about an itchy feeling on skin also do the same in the gut, so these patients are essentially suffering from a 'gut itch’.
Stuart Brierley
It seems that these “itch” receptors are more common in people with IBS than in people without the condition. The more of these receptors present, the more neurons are activated and the more pain is felt.
Study author Stuart Brierley says the itch receptor in the gut could provide a new way of targeting the underlying cause of gut pain, rather than using conventional pain relief drugs such as opiates, which do not actually resolve the problem.
He adds that the team has now translated the findings to human tissue tests and that they now hope to help develop a treatment that people with IBS could take as an oral medication. "
The study in more detail
Itch and pain are detected by neurons called primary sensory dorsal root ganglions (DRGs). These neurons project from peripheral tissues into the spinal cord, where they release neurotransmitters that excite spinal neurons.
Several itch mechanisms in the skin have been described and one of them involves the Mas-gene-related G protein-coupled receptor proteins MrgprA3 and MrgprC11. Another mechanism involves the bile acid receptor Tgr5.
MrgprA3 and MrgprC11 are expressed by subsets of sensory DRG neurons innervating the skin and Tgr5 is also expressed by a sub-population of peptidergic DRG neurons.
However, it remains unclear whether Tgr5 and Mrgpr mechanisms co-exist within the same DRG neuronal populations or whether they exist in and recruit different types of DRG neurons.
As reported in the journal JCI insight, Brierley and colleagues showed that Tgr5 and the two Mrgpr receptors are all expressed by colon-innervating DRG neurons, in both distinct and overlapping subsets of sensory DRG neurons. Their activation caused fundamental signaling changes within colonic afferent pathways in both healthy and disease states.
The team says the findings support the existence of an irritant-sensing system in the colon that is a visceral representation of the itch pathways found in skin, thereby contributing to the sensory disturbances accompanying common intestinal disorders.
The “wasabi receptor”
Brierley says the pain that people with IBS experience occurs when the itch receptors are coupled with what is known of as the 'wasabi receptor' in the nervous system, which is responsible for the reaction that is usually seen when people consume the Japanese condiment.
"If you think about what happens when you eat wasabi, it activates a receptor on the nerves and sends a pain signal - that's exactly what's happening within in their gut as they experience an itchy effect or wasabi effect in the gut."
Having shown that these mechanisms contribute to chronic gut pain, he continues, the team can now try to find out how to block the receptors and stop the “gut itch” signal traveling from the gut to the brain.
This will be a far better solution than the problems currently presented by opioid treatments."
Stuart Brierley
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