Tag Archives: genetics

Pain killers

You might not like it, but you need to feel pain. It’s important. It helps to keep you safe by letting you know when something is wrong. You experience pain through specialised nerve cell endings called nociceptors. You will find these throughout your body, but some areas, such as your skin, have more than others. They alert you to different causes of pain which could harm you, such as extreme temperatures, pressure, damaging chemicals and infection.

So how does a painful sensation tell your brain you’re in trouble?

You accidently put your hand on a hot hob… ouch! Your nociceptors respond to this pain and create an electrical signal using special proteins called sodium channels. These channels are like gates in the membrane that surrounds the nerve cell. When a cause of pain – such as hand on hob – triggers a signal, these gates open and let in a flood of positively charged sodium ions. This changes the electrical charge of the nerve and a signal travels from nerve to nerve, up the spinal cord and into your brain to alert it to the pain.

We have nine different types of sodium channels, but only one is particularly important for pain – Nav 1.7. This channel is essential to transmit pain signals. Each channel has its own gene, which provides the instructions for how the channel should work. The gene for channel Nav 1.7 is called SCN9A. Mutations to this gene effect how you experience pain. Some mutations can make people super-sensitive to pain, while other mutations can cause people to feel no physical pain at all.

A rare mutation to the SCN9A gene, called a non-sense mutation, causes the sodium channel to stop working. This means that pain signals from the body aren’t transmitted to the brain. People with this genetic mutation are unable to feel any physical pain and can’t smell, but are otherwise healthy. Fewer than one in a million people in the UK can’t feel pain because of SCN9A mutations.

Researchers want to recreate the effect of the mutation to treat pain in others. If scientists can isolate a molecule that can block pain signals in the same way they will have a powerful painkiller.

Oddly enough research reveals that molecules in toxic venom from snails, snakes, scorpions and spiders can block human sodium channels. If scientists can find the venom component that only blocks pain channel Nav 1.7 it could mean pain relief without serious side-effects. This is because Nav 1.7 is only responsible for pain and smell, unlike other targets for pain-relief drugs, such as opioid receptors. As well as pain relief your opioid receptors are linked to your emotions, and things you do automatically such as breathing.

A drug which only targets Nav 1.7 would specifically target the experience of pain.

Could venom be the ‘wonder drug’ of the future?

‘Yes!’ says Pierre Escoubas, Founder of Venome Tech.

‘Your nerves have many sodium channels to communicate between the brain and body. Each has a specific function. Blocking a channel other than pain channel Nav 1.7 could have serious effects on the heart, muscles or nervous system. A treatment with too general a target could be fatal.’

‘Venom-derived molecules can be very selective. This makes them the ‘magic bullet’ of potential drugs, as they hit a specific target without undesirable side effects.’

Venom might be the source of a future drug for pain relief. But it’s not as easy as just milking a spider…

‘The big problem is that the peptides (protein parts) we have isolated so far are not selective enough. They strongly block Nav 1.7 but they block other channels as well’ explains Glenn King, Professor of Molecular Bioscience at the University of Queensland.

‘Right now we have found a good candidate which is very effective at blocking Nav 1.7. Unfortunately it also blocks Nav 1.6, which might cause undesired side-effects. So, we’re hoping to tweak the molecular structure a little and get the selectivity required for a perfect painkiller.’

Could this pain killer be too effective?

Pain may not be pleasant but it helps keep you from hurting yourself too. If the drug blocks all pain could it be so good it’s bad?

’I think we would only need to worry about a drug this effective being too good if the effects were permanent’ says Glenn King. ‘The molecules we’re looking at have a limited life in the bloodstream and eventually break down. Patients would probably need regular top-ups.’

Venom has a lot of potential, but it’s not the only possible future for pain relief.

‘Another type of pain transmitter in the body is the transient receptor potential (TRP) channels’ explains Julie Keeble, a pharmaceutical researcher at Kings College London.

‘As part of my research I have been studying the role of TRP channels in painful inflammation, such as the chronic pain associated with arthritis. Some TRP channels are affected by simple kitchen ingredients – like hot chilli peppers and mustard oil, but they can also be activated by chemicals that are produced during pain. Drugs to target these channels are still progressing through clinical trials, but they may offer new hope for chronic pain patients.’

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A life without pain

Most of us don’t like feeling pain, but we know how important it is. Pain is the warning signal that lets us know when we’re injured or ill.

One of the extraordinary people we came across during our research was Steven. He is ordinary in almost every way, but unlike most of us he has a rare condition that means he can’t feel any pain.

‘When I’m overcome with nausea, exhaustion or aches it may just be a cold, but it could be deadly serious like a burst appendix. My life is full of potentially dangerous situations because I don’t feel pain.’

Clinical geneticist Geoff Woods was among the first to report that some people who don’t feel pain carry a genetic mutation that affects the pain-sensing nerves in their bodies. None of their pain receptors send signals to their brains. Geoff explains:

‘Some painless people have a small mutation in an area of their genetic code that is essential to make a pain channel in their nerves. Without the channel it’s impossible to send pain signals to the brain. By studying people like Steven’s DNA we can eventually understand why he doesn’t feel pain. More importantly, it tells us how the rest of us do.’

Powerful gene sequencers such as this one can read an entire human genome in one day and identify the no-pain genetic mutation. We’ve got our hands on this clever piece of kit for Pain Less.

Natural born painkillers

Researchers are now working to understand exactly how this mutation blocks pain signals to the brain to try and mimic it, and create the ultimate painkiller.

They may have found the answer from a very unusual source – snake and spider venom. Venom is a cocktail of different molecules used to incapacitate prey and deter predators.

Biochemist Glenn King is investigating some molecules in this noxious mix that stop pain in the same way as the no-pain genetic mutation. These molecules block a channel in the body’s nerves to stop pain signals from reaching the brain.

So rather than start from scratch to synthesise these complex molecules, pharmaceutical companies are looking to venomous sea snails, spiders, snakes and scorpions to provide vital ingredients for the next generation of painkillers.

Jasmine’s favourite find

Jasmine Spavieri, one of our Assistant Content Developers, describes how she sourced one of the most striking objects in our exhibition…

‘One exceptional story we found was that of Steve Trim, a former chronic pain patient and a pain researcher. After finding a treatment that worked to cure his pain, Steve was inspired to accept a job working in pain research.

‘He discovered that the use of venom as a potential medication is a growing field of research. He decided to start his own biotech company – or as we like to call it “venom farm” – and is now the director of Venomtech. His laboratory provides an array of “fresh” venoms, from snakes to spiders and scorpions. Steve also gives educational talks to school groups and answered the questions of our young participatory group from Langley Academy.

‘Steve has been kind enough to provide us with what I think is one of our coolest objects, the skin and fangs of a huge tarantula, along with some milking equipment!’

I’m relieved it’s not a snake – they give me the heebie-jeebies.