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UK funding (£998,677): MICA: A comprehensive genomic and functional approach to discover new ion channel targets for human pain treatment Ukri1 Oct 2012 UK Research and Innovation, United Kingdom
Overview
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MICA: A comprehensive genomic and functional approach to discover new ion channel targets for human pain treatment
| Abstract | Pain is common, affecting 1 in 6 adults. Pain is also often complex; the sudden pain of a cut, burn or fractured bone (nociceptive pain), or the longer term aching pain associated with cancer or chronic injuries (neuropathic pain) or, more commonly, a mixture of both types. It is currently impossible to tell how much pain a person is suffering or to compare this pain accurately between people. Furthermore it can be difficult to determine the origin of pain, and we know that once pain has started it can become self-perpetuating probably due to secondary changes in the spinal cord or brain. We also all have experienced the depression and debilitation pain can cause if it is either severe or long lasting. Finally, pain treatment if often successful for mild pain and short lived nociceptive pain; however treatments for chronic pain are far less effective and often lead to side effects. We, and others, have previously shown that some members of a class of genes called ion channels are essential to produce pain. Ion channel genes code for proteins that sit on the surface of neurons and either detect pain and turn this into a voltage signal, or respond to other proteins that detect pain and amplify their signal. We found that an ion channel gene called SCN9A can control all nociceptive pain felt (causing a condition called Congenital Insensitivity to Pain in people with no working SCN9A gene) and that another ion channel gene HCN2 controls neuropathic pain (this time in mice studies, where the mice with no HCN2 gene did not feel any neuropathic pain). In both people with no SCN9A and mice with no HCN2 the lack of pain sensing was the only feature. This is very important and suggests that if you could design a drug to block SCN9A and/or HCN2 you would have a new type of analgesic without side effects. We now want to look for further ion channels that are part of the mechanism that make people feel pain. We are taking a novel approach by using three groups of people who feel extremes of pain: one group are people with severe neuropathic pain who get referred to a specialized pain clinic in Cambridge after other approaches have failed. These people have multiple reasons why they first experienced pain but are distinguished by their persistent pain becoming more severe and stopping them working and functioning normally. This group is currently extremely difficult to treat and is a significant problem for our society and the NHS. Our second group consists of women who don't need pain relief during their first delivery - constituting only 1% of women in the Rosie Maternity Hospital in Cambridge. We don't know whether these women are stoical, just determined not to have any drugs, have a quick labour, or have a very high pain threshold (probably a mix), but most importantly some of these women have other family members who similarly didn't need analgesia during their first labour strongly suggesting that this may be a genetic trait. Our third group if of very rare families with extremes of pain sensing - either feeling no pain or very early onset of severe debilitating pain. It is from researching this group that we found SCN9A. We will select the 300 people from these three cohorts with the most severe pain findings and sequence all of their ion channel genes. What we are looking for is changes in ion channel genes that will change the way they work. If we find an ion channel gene change in a patient, say with severe neuropathic pain, and then find that in the laboratory that the mutation alters the way the ion channel works, then that ion channel could be important for pain control in humans with neuropathic pain. We will need to perform further studies on each gene we identify to provide further proof of its role in pain. Each ion channel we identify has the potential to generate new analgesics leading to better pain control for our patients. |
| Category | Research Grant |
| Reference | MR/J012742/1 |
| Status | Closed |
| Funded period start | 01/10/2012 |
| Funded period end | 30/06/2016 |
| Funded value | £998,677.00 |
| Source | https://gtr.ukri.org/projects?ref=MR%2FJ012742%2F1 |
Participating Organisations
| University of Cambridge | |
| University of Oxford | |
| Neusentis limited |
The filing refers to a past date, and does not necessarily reflect the current state. The current state is available on the following page: University of Cambridge, Cambridge.
