 Y tîm hwn yn roi ddweud o golygu яwtyn yw'r ddweud. Ddiwethaf a ddweud fathu yw'r ddweud o'r ddweud o'r ddweudio, ac rwy'n cael ddweud o bwysig. Dwi'n mynd i ddigonанаeth a ddweud o'r ddweud, i ddweud y cyffredinnig mae'r ddweud yn cael ffioedd, mae ddweud rŵr y ddwy'n cael ei fod yn gwisir. Dwi'n cael rŵr dod eich ddweud fel y mae hwn erioed yn gweithio wahanol was too hot so you put it down before you generated a large burn injury and damaged your body more substantially. So that's the good part of the pain system working as a detect and protect system. The problem is that sometimes this system can go wrong and it tells about problems that don't exist or it amplifies the signal an awful lot. So if we consider chronic pain conditions such as rheumatoid arthritis, irritable bowel syndrome or osteoarthritis, here there is an ongoing pain which serves no protective function and broadly speaking in the UK the adult population will experience chronic pain so pain lasting more than three months can be as high as 40% so there's a good chance that any individual during their lifetime could experience chronic pain and the problem we currently have is the therapeutics that clinicians have available to treat chronic pain are quite limited. We have drugs such as opioids so things like morphine which although they're quite good in post-operative pain relief they're addictive you quite often have to increase the dose over time they cause side effects such as constipation but it's the side effects that are really the major issue. What you want to do is use a drug that causes pain relief but doesn't cause other things so in the case of opioids there should be addiction or constipation as two examples. So because we've got this limited number of therapeutics available what we try to do is study how the pain system works what goes wrong in chronic disease and can we therefore identify new pain targets for the development of new pain killers. Now the naked mind is particularly interesting as a model organism here because something that it displays in an unusual way is what we call inflammatory pain so inflammatory pain is with you receive an injury the area becomes red and swollen and your sensitivity in that area increases and again from an evolutionary point to you that's a really good thing past the body is damaged you get increased sensitivity you'll look after it until it heals but sometimes that healing process doesn't happen properly and then you end up with this prolonged chronic pain and the naked mind shows very unusual inflammatory pain sensitivity in that it often doesn't show the same the same level of extreme pain and one thing we think is one reason for that we think is because the naked mind doesn't respond to acid as an unpleasant noxious stimulus so quite often areas of inflammation will develop a level of acidity and acid activates nerves to make you go ouch so think of being in the kitchen lemon juice or vinegar if you spill them into cut skin your generator pain signal and the naked mind doesn't respond at all to acid as an unpleasant stimulus and we think this is because the naked mind lives underground in large colonies and they nest in chambers that are very small so lots of animals breathing all together in a small chamber will cause an increase in the carbon dioxide concentration because carbon dioxide is what we exhale when we breathe carbon dioxide will mix with water to produce carbonic acid so any mucous membranes in the eyes and the nose that's where you could generate carbonic acid which will drive pain so the naked mind is in this quite safe environment but quite acidic environment and over time with revolution it seems their nervous system adapted to no longer feel acid as being unpleasant and we were able to take the naked mind demonstrated the behavioural level they didn't show any behavioural response they really didn't care you inject them with a small amount of acid they just walk off as if nothing happened we could then show at the nervous system level how the nerves reacted differently and we were then able to identify a single gene that was altered in the naked mole rat that could account this difference in acid sensitivity now interestingly there's one gene that we identified the naked mole rat had been identified by others in humans and in mice as being important in pain processing so it's really interested in the naked mole rat from a completely different angle was able to shed light from a different way and how this one gene is really important for pain processing so if you were to go to the dentist and they're going to do something nasty like doing a tooth extraction hopefully before they do that they'll administer a local anesthetic and what the anesthetic does is it just prevents electrical signals traveling in nerves so it doesn't matter what stimulation you receive at the site of where the dentist is working that signal just cannot travel along the nerve and what we see in the naked mole rat is this gene has been altered such that acid acts like a local anesthetic on this gene because this one particular gene is important for sending electrical signals and what happens is the mutation the naked marat has means that when acid acts upon it it switches it off in the same way that a local anesthetic does so therefore acid switches naked mole rat neurons off whereas it excites neurons in mice and humans so the gene in the naked marat controls their acid insensitivity but evidence from humans and from mouse workers demonstrated that this gene is particularly important in pain processing in general and it's a gene that's one of a family of many that control the electrical excitability in nerves specifically how signals travel from A to B but when you take a local anesthetic at the dentist that's a drug that acts in a non-selective way it acts on all genes in this family to switch off the function of all of them now the particular gene we're interested in pain is nav 1.7 that's the protein name and that protein is one of a family of nine but its expression within the body is limited to a certain number of parts of it and one major area is the pain system the idea is if you've developed a drug that specifically blocks the activity of nav 1.7 you'll switch off activity in the pain system but you don't have major effects on other bits of the nervous system so again going back to the local anesthetic at the dentist you want the pain relief but you don't want all the numbness and the inability to feel anything there's a difference between touch and pain so the reason people have slurred speech after they come out the dentist is because they've lost the ability to control perhaps their tongue and their cheek muscles properly and that's because local anesthetics switch off these voltage gated sodium channels in all nerves whereas this gene that encodes the protein nav 1.7 is only really present in parts of the nervous system to do with pain processing so we hope that if we can block its function you'd have a drug that causes pain relief but doesn't come associated with the side effects of blocking other versions of this protein elsewhere in the body.