A receptor that is responsible for our sense of touch and temperature, and which researchers have now found to be present in our colon, could provide a target for treating chronic pain associated with gastrointestinal disorders such as irritable bowel syndrome.

A study led by Hongzhen Hu, PhD, at Washington University, and Nick Spencer, PhD, at Flinders University, identified the presence of Piezo2, the subject of the 2021 Nobel Prize in Physiology or Medicine, now known to be responsible for sensing light touch on our skin. “In discovering that this receptor is also in our gut, there’s the potential that selectively targeting these channels could be used for long-term silencing of pain sensations from internal organs, without the need for frequent consumption of opiate pain medications,” said Spencer, a Matthew Flinders Professor in the College of Medicine and Public Health.

Spencer, Hu and colleagues reported on their findings, including experiments in mouse models of pain, in a paper in Neuron titled “Piezo2 channels expressed by colon-innervating TRPV1-lineage neurons mediate visceral mechanical hypersensitivity.”

Inflammatory and functional gastrointestinal disorders such as irritable bowel syndrome (IBS) and obstructive bowel disorder (OBD) underlie the most prevalent forms of visceral pain, the authors wrote. “Chronic pain from internal organs, such as the gut or bladder, is notoriously difficult to treat,” Spencer noted. “Opiates, including morphine and their derivates have been commonly used to treat a variety of types of pain but visceral pain doesn’t respond well to the treatment and the drugs are highly addictive with a multitude of side effects.”

The authors say the availability of selective pain medications for the gut has been hindered by a lack of understanding about how sensory nerves communicate pain sensations from the gut to the brain. “Mechanisms underlying visceral pain are poorly understood, and the resulting lack of effective clinical management represents a major unmet medical problem,” they pointed out. “Remarkably, unlike chronic somatic pain, which is a focus of research and drug development, visceral pain is relatively neglected despite its greater clinical need.”

The team’s newly reported study demonstrated that the mechanosensitive Piezo2 channel, expressed by TRPV1-lineage neurons, is critically involved in the generation of visceral mechanical nociception under physiological conditions, and mechanical hypersensitivity in mouse models of IBS and partial colon obstruction (PCO). “… our results demonstrate that Piezo2 channels expressed by TRPV1-lineage visceral nociceptors mediate a large component of acute visceral mechanical nociception under physiological conditions,” they stated. “Importantly, Piezo2 channels expressed by TRPV1-lineage visceral nociceptors also emerged as a critical mediator of pathologic visceral mechanical hypersensitivity in mouse models of IBS and PCO, thus identifying Piezo2 channel as a potential therapeutic target for the treatment of chronic visceral pain.”

It was previously known that many different ion channels are located on the ‘pain-sensing’ neurons that communicate from the gut to the brain, but the new study has now identified the major ion channel in the colon that responds to mechanical stimulation leading to the sensation of pain, said Spencer. “Furthermore, we have discovered that the major ion channel that responds to this mechanical pain is a member of the Piezo ion channel, specifically Piezo2. From this knowledge we can focus on targeting these channels to silence the pain sensations and hopefully produce a treatment for visceral pain, common in conditions such as irritable bowel syndrome, endometriosis or abdominal cancers, while avoiding the devastating side effects of opioids.”

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