Pain is more than a signal that something is going wrong. In the intestines, pain immediately provides protection and recovery. Painkillers, in this case at least, could therefore be doing more harm than good.
When your finger touches a flame, for instance, a nerve stimulus goes to the brain that signals that something is painfully wrong. After which, the brain sends a signal to the arm and withdraws the finger from the fire.
That's what the textbooks say about pain, and its usefulness: it is the alarm bell that ensures that we limit body damage as much as possible and avoid danger.
But pain hurts more than that, according to recent research. In the intestines, pain along a direct line causes repair of damage, as well as the protection against diseases, without the intervention of the brain.
Uses of mucus
A research group from Harvard Medical School in the US recently published in the journal Cell that certain neurons in the intestinal wall regulate the production of the mucous layer – which is essential for protecting the intestinal wall and for a healthy intestinal flora. That mucus is produced by so-called mucus cup cells. And they appear to be controlled by nociceptors, neurons that are sensitive to pain stimuli.
It sounds strange that pain has such a direct local effect. But for the researchers, this was not unexpected, says Daping Yang, a young Chinese researcher at Harvard and first author of this study. "Those neurons, those nociceptors, are in the epithelium, the inner layer of the intestinal wall and have contact with other cells there through their offshoots,” he is quoted as saying so by RTBF.
“Nociceptors not only transmit stimuli to the brain, but also produce proteins to those offshoots that act as signalling substances. That was already known. We have now mapped out what one of these signal substances does, and how exactly that works."
The researchers bred mice that lacked those nociceptors and saw that in those animals the mucous layer in the intestines deteriorated. They then found out which signal substance is sent by the nociceptors to the mucous cup cells and with which receptor those cup cells pick up that signal.
Nociceptors signals
It's the first time that the control of mucus production by pain-sensitive nerve cells has been demonstrated, Yang says. But it's not the only button those nerve cells have. Coincidence or not, in the same edition of Cell appeared a study by another American research group – at Weill Cornell Medicine, a medical school in New York – in which it was shown that other nociceptors release a signalling substance that promotes the growth of healthy microorganisms, the intestinal flora. The exact operation of that signal has not yet been clarified.
"That research complements ours," says Isaac Chiu, research leader at Harvard Medical School. "These researchers have shown that the intestinal flora deteriorates when pain-sensitive nerve cells disappear. We also see this in our mice that lack pain-sensitive nerve cells."
A diluted mucous layer on the intestinal wall and a deteriorated intestinal flora are the symptoms of so-called inflammatory bowel diseases, such as Crohn's and ulcerative colitis. The underlying cause now seems to lie in the loss of pain stimuli that keep the intestine healthy.
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This discovery changes the way we think about these common intestinal diseases and about their treatment. Gut patients often suffer pain, but fighting it could make their condition worse, the researchers say.
The key question now is what exactly pain medication does. Does it only block the sensation of pain in the brain or also the healing effect of pain neurons in the intestine? In the first case you help the patient, in the second case certainly not.
"We don't know exactly yet,” says Isaac Chiu. “The principle action of painkillers is that they block the sensation of pain. But, as mentioned, those pain neurons are also active when we do not feel pain. Whether pain medication also disrupts that, we now have to find out."
"We know that powerful painkillers such as opiates slow down the functioning of the intestine and affect the intestinal flora. But it may very well be that other drugs only block the sensation of pain and not the action of pain neurons in the intestines. We have to figure that out. But the essential role of pain neurons in the intestinal wall should make us cautious about prescribing pain medication."
