̽��ֱ�� of Cambridge - pain

Robotic nerve ‘cuffs’ could help treat a range of neurological conditions

sc604 — Fri, 26 Apr 2024 08:55:34 +0000

̽��ֱ��researchers, from the ̽��ֱ�� of Cambridge, combined flexible electronics and soft robotics techniques to develop the devices, which could be used for the diagnosis and treatment of a range of disorders, including epilepsy and chronic pain, or the control of prosthetic limbs.

Current tools for interfacing with the peripheral nerves – the 43 pairs of motor and sensory nerves that connect the brain and the spinal cord – are outdated, bulky and carry a high risk of nerve injury. However, the robotic nerve ‘cuffs’ developed by the Cambridge team are sensitive enough to grasp or wrap around delicate nerve fibres without causing any damage.

Tests of the nerve cuffs in rats showed that the devices only require tiny voltages to change shape in a controlled way, forming a self-closing loop around nerves without the need for surgical sutures or glues.

̽��ֱ��researchers say the combination of soft electrical actuators with neurotechnology could be an answer to minimally invasive monitoring and treatment for a range of neurological conditions. ̽��ֱ��results are reported in the journal Nature Materials.

Electric nerve implants can be used to either stimulate or block signals in target nerves. For example, they might help relieve pain by blocking pain signals, or they could be used to restore movement in paralysed limbs by sending electrical signals to the nerves. Nerve monitoring is also standard surgical procedure when operating in areas of the body containing a high concentration of nerve fibres, such as anywhere near the spinal cord.

These implants allow direct access to nerve fibres, but they come with certain risks. “Nerve implants come with a high risk of nerve injury,” said Professor George Malliaras from Cambridge’s Department of Engineering, who led the research. “Nerves are small and highly delicate, so anytime you put something large, like an electrode, in contact with them, it represents a danger to the nerves.”

“Nerve cuffs that wrap around nerves are the least invasive implants currently available, but despite this they are still too bulky, stiff and difficult to implant, requiring significant handling and potential trauma to the nerve,” said co-author Dr Damiano Barone from Cambridge’s Department of Clinical Neurosciences.

̽��ֱ��researchers designed a new type of nerve cuff made from conducting polymers, normally used in soft robotics. ̽��ֱ��ultra-thin cuffs are engineered in two separate layers. Applying tiny amounts of electricity – just a few hundred millivolts – causes the devices to swell or shrink.

̽��ֱ��cuffs are small enough that they could be rolled up into a needle and injected near the target nerve. When activated electrically, the cuffs will change their shape to wrap around the nerve, allowing nerve activity to be monitored or altered.

“To ensure the safe use of these devices inside the body, we have managed to reduce the voltage required for actuation to very low values,” said Dr Chaoqun Dong, the paper’s first author. “What's even more significant is that these cuffs can change shape in both directions and be reprogrammed. This means surgeons can adjust how tightly the device fits around a nerve until they get the best results for recording and stimulating the nerve.”

Tests in rats showed that the cuffs could be successfully placed without surgery, and formed a self-closing loop around the target nerve. ̽��ֱ��researchers are planning further testing of the devices in animal models, and are hoping to begin testing in humans within the next few years.

“Using this approach, we can reach nerves that are difficult to reach through open surgery, such as the nerves that control, pain, vision or hearing, but without the need to implant anything inside the brain,” said Barone. “ ̽��ֱ��ability to place these cuffs so they wrap around the nerves makes this a much easier procedure for surgeons, and it’s less risky for patients.”

“ ̽��ֱ��ability to make an implant that can change shape through electrical activation opens up a range of future possibilities for highly targeted treatments,” said Malliaras. “In future, we might be able to have implants that can move through the body, or even into the brain – it makes you dream how we could use technology to benefit patients in future.”

̽��ֱ��research was supported in part by the Swiss National Science Foundation, the Cambridge Trust, and the Engineering and Physical Sciences Research Council (EPSRC), part of UK Research and Innovation (UKRI).

Reference:
Chaoqun Dong et al. ‘Electrochemically actuated microelectrodes for minimally invasive peripheral nerve interfaces.’ Nature Materials (2024). DOI: 10.1038/s41563-024-01886-0

Researchers have developed tiny, flexible devices that can wrap around individual nerve fibres without damaging them.

̽��ֱ��ability to make an implant that can change shape through electrical activation opens up a range of future possibilities for highly targeted treatments

George Malliaras

XH4D via iStock / Getty Images Plus

Illustration of the human nervous system

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Mole-rats: meet the Ugly Naked Guys

jg533 — Tue, 06 Sep 2022 08:38:57 +0000

Understanding their weirdness could help prevent and better treat human illnesses like arthritis and cancer.

Inflatable, shape-changing spinal implants could help treat severe pain

sc604 — Fri, 25 Jun 2021 17:14:34 +0000

A team of engineers and clinicians has developed an ultra-thin, inflatable device that can be used to treat the most severe forms of pain without the need for invasive surgery.

Nature’s epidural: Genetic variant may explain why some women don’t need pain relief during childbirth

cjb250 — Tue, 21 Jul 2020 15:00:21 +0000

Childbirth is widely recognised as a painful experience. However, every woman’s experience of labour and birth is unique, and the level of discomfort and pain experienced during labour varies substantially between women.

A collaboration between clinicians and scientists based at Addenbrooke’s Hospital, part of Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust (CUH), and the ̽��ֱ�� of Cambridge sought to investigate why some mothers report less pain during labour.

A group of women was recruited and characterised by the team led by Dr Michael Lee from the ̽��ֱ��’s Division of Anaesthesia. All the women had carried their first-born to full term and did not request any pain relief during an uncomplicated vaginal delivery. Dr Lee and colleagues carried out a number of tests on the women, including applying heat and pressure to their arms and getting them to plunge their hands into icy water.

Compared to a control group of women that experienced similar births, but were given pain relief, the test group showed higher pain thresholds for heat, cold and mechanical pressure, consistent with them not requesting pain relief during childbirth. ̽��ֱ��researchers found no differences in the emotional and cognitive abilities of either group, suggesting an intrinsic difference in their ability to detect pain.

“It is unusual for women to not request gas and air, or epidural for pain relief during labour, particularly when delivering for the first time,” said Dr Lee, joint first author. “When we tested these women, it was clear their pain threshold was generally much higher than it was for other women.”

Next, senior co-author, Professor Geoff Woods, and his colleagues at the Cambridge Institute for Medical Research sequenced the genetic code of both groups of women and found that those in the test group had a higher-than-expected prevalence of a rare variant of the gene KCNG4. It’s estimated that one approximately 1 in 100 women carry this variant.

KCNG4 provides the code for the production of a protein that forms part of a ‘gate’, controlling the electric signal that flows along our nerve cells. As the joint first author Dr Van Lu showed, sensitivity of this gatekeeper to electric signals that had the ability to open the gate and turn nerves on was reduced by the rare variant.

This was confirmed in a study involving mice led by Dr Ewan St. John Smith from the Department of Pharmacology, who showed that the threshold at which the ‘defective’ gates open, and hence the nerve cell switches ‘on’, is higher – which may explain why women with this rare gene variant experience less pain during childbirth.

Dr St. John Smith, senior co-author, explained: “ ̽��ֱ��genetic variant that we found in women who feel less pain during childbirth leads to a ‘defect’ in the formation of the switch on the nerve cells. In fact, this defect acts like a natural epidural. It means it takes a much greater signal – in other words, stronger contractions during labour – to switch it on. This makes it less likely that pain signals can reach the brain.”

“Not only have we identified a genetic variant in a new player underlying different pain sensitivities,” added senior co-author Professor Frank Reimann, “but we hope this can open avenues to the development of new drugs to manage pain.”

“This approach of studying individuals who show unexpected extremes of pain experience also may find wider application in other contexts, helping us understand how we experience pain and develop new drugs to treat it,” said Professor David Menon, senior co-author.

̽��ֱ��research was support by the Addenbrooke’s Charitable Trust, the National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome, Rosetrees Trust and the BBSRC.

Reference
Lee, M.C. et al (2020). Human labour pain is influenced by the voltage-gated potassium channel Kv6.4 subunit. Cell Reports; 21 July 2020; DOI: 10.1016/j.celrep.2020.107941

Women who do not need pain relief during childbirth may be carriers of a key genetic variant that acts a natural epidural, say scientists at the ̽��ֱ�� of Cambridge. In a study published today in the journal Cell Reports, the researchers explain how the variant limits the ability of nerve cells to send pain signals to the brain.

This [variant] acts like a natural epidural. It means it takes a much greater signal – in other words, stronger contractions during labour – to switch it on. This makes it less likely that pain signals can reach the brain

Ewan St. John Smith

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Mother and newborn baby

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New 3D imaging analysis technique could lead to improved arthritis treatment

sc604 — Mon, 18 Jun 2018 09:00:00 +0000

̽��ֱ��technique, which detects tiny changes in arthritic joints, could enable greater understanding of how osteoarthritis develops and allow the effectiveness of new treatments to be assessed more accurately, without the need for invasive tissue sampling. ̽��ֱ��results are published in the journal Scientific Reports.

Osteoarthritis is the most common form of arthritis in the UK. It develops when the articular cartilage that coats the ends of bones, and allows them to glide smoothly over each other at joints, is worn down, resulting in painful, immobile joints. Currently there is no recognised cure and the only definitive treatment is surgery for artificial joint replacement.

Osteoarthritis is normally identified on an x-ray by a narrowing of the space between the bones of the joint due to a loss of cartilage. However, x-rays do not have enough sensitivity to detect subtle changes in the joint over time.

“In addition to their lack of sensitivity, two-dimensional x-rays rely on humans to interpret them,” said lead author Dr Tom Turmezei from Cambridge’s Department of Engineering. “Our ability to detect structural changes to identify disease early, monitor progression and predict treatment response is frustratingly limited by this.”

̽��ֱ��technique developed by Turmezei and his colleagues uses images from a standard computerised tomography (CT) scan, which isn’t normally used to monitor joints, but produces detailed images in three dimensions.

̽��ֱ��semi-automated technique, called joint space mapping (JSM), analyses the CT images to identify changes in the space between the bones of the joint in question, a recognised surrogate marker for osteoarthritis. After developing the algorithm with tests on human hip joints from bodies that had been donated for medical research, they found that it exceeded the current ‘gold standard’ of joint imaging with x-rays in terms of sensitivity, showing that it was at least twice as good at detecting small structural changes. Colour-coded images produced using the JSM algorithm illustrate the parts of the joint where the space between bones is wider or narrower.

“Using this technique, we’ll hopefully be able to identify osteoarthritis earlier, and look at potential treatments before it becomes debilitating,” said Turmezei, who is now a consultant at the Norfolk and Norwich ̽��ֱ�� Hospital’s Department of Radiology. “It could be used to screen at-risk populations, such as those with known arthritis, previous joint injury, or elite athletes who are at risk of developing arthritis due to the continued strain placed on their joints.”

While CT scanning is regularly used in the clinic to diagnose and monitor a range of health conditions, CT of joints has not yet been approved for use in research trials. According to the researchers, the success of the JSM algorithm demonstrates that 3D imaging techniques have the potential to be more effective than 2D imaging. In addition, CT can now be used with very low doses of radiation, meaning that it can be safely used more frequently for the purposes of ongoing monitoring.

“We’ve shown that this technique could be a valuable tool for the analysis of arthritis, in both clinical and research settings,” said Turmezei. “When combined with 3D statistical analysis, it could be also be used to speed up the development of new treatments.”

Tom Turmezei acknowledges the Wellcome Trust for research funding. Ken Poole acknowledges the support of the Cambridge NIHR Biomedical Research Centre.

Reference
T.D. Turmezei et al. ‘A new quantitative 3D approach to imaging of structural joint disease.’ Scientific Reports (2018). DOI: 10.1038/s41598-018-27486-y

An algorithm to monitor the joints of patients with arthritis, which could change the way that the severity of the condition is assessed, has been developed by a team of engineers, physicians and radiologists led by the ̽��ֱ�� of Cambridge.

Using this technique, we’ll hopefully be able to identify osteoarthritis earlier, and look at potential treatments before it becomes debilitating.

Tom Turmezei

Hip, knee and ankle joints analysed by the JSM algorithm

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Identification of brain region responsible for alleviating pain could lead to development of opioid alternatives

sc604 — Tue, 27 Feb 2018 08:00:00 +0000

̽��ֱ��team, led by the ̽��ֱ�� of Cambridge, have pinpointed an area of the brain that is important for endogenous analgesia – the brain’s intrinsic pain relief system. Their results, published in the open access journal eLife, could lead to the development of pain treatments that activate the painkilling system by stimulating this area of the brain, but without the dangerous side-effects of opioids.

Opioid drugs such as oxycodone, hydrocodone and fentanyl hijack the endogenous analgesia system, which is what makes them such effective painkillers. However, they are also highly addictive, which has led to the opioid crisis in the United States, where drug overdose is now the leading cause of death for those under 50, with opioid overdoses representing two-thirds of those deaths.

“We’re trying to understand exactly what the endogenous analgesia system is: why we have it, how it works and where it is controlled in the brain,” said Dr Ben Seymour of Cambridge’s Department of Engineering, who led the research. “If we can figure this out, it could lead to treatments that are much more selective in terms of how they treat pain.”

Pain, while unpleasant, evolved to serve an important survival function. After an injury, for instance, the persistent pain we feel saps our motivation, and so forces us towards rest and recuperation which allows the body to use as much energy as possible for healing.

“Pain can actually help us recover by removing our drive to do unnecessary things - in a sense, this can be considered ‘healthy pain’,” said Seymour. “So why might the brain want to turn down the pain signal sometimes?”

Seymour and his colleagues thought that sometimes this ‘healthy pain’ could be a problem, especially if we could actively do something that might help - such as try and find a way to cool a burn.

In these situations, the brain might activate the pain-killing system to actively look for relief. To prove this, and to try and identify where in the brain this system was activated, the team designed a pair of experiments using brain scanning technology.

In the first experiment, the researchers attached a metal probe to the arm of a series of healthy volunteers - and heated it up to a level that was painful, but not enough to physically burn them. ̽��ֱ��volunteers then played a type of gambling game where they had to find which button on a small keypad cooled down the probe. ̽��ֱ��level of difficulty was varied over the course of the experiments - sometimes it was easy to turn the probe off, and sometimes it was difficult. Throughout the task, the volunteers frequently rated their pain, and the researchers constantly monitored their brain activity.

̽��ֱ��results found that the level of pain the volunteers experienced was related to how much information there was to learn in the task. When the subjects were actively trying to work out which button they should press, pain was reduced. But when the subjects knew which button to press, it wasn't. ̽��ֱ��researchers found that the brain was actually computing the benefits of actively looking for and remembering how they got relief, and using this to control the level of pain.

Knowing what this signal should look like, the researchers then searched the brain to see where it was being used. ̽��ֱ��second experiment identified the signal in a single region of the prefrontal cortex, called the pregenual cingulate cortex.

“These results build a picture of why and how the brain decides to turn off pain in certain circumstances, and identify the pregenual cingulate cortex as a critical ‘decision centre’ controlling pain in the brain,” said Seymour.

This decision centre is a key place to focus future research efforts. In particular, the researchers are now trying to understand what the inputs are to this brain region, if it is stimulated by opioid drugs, what other chemical messenger systems it uses, and how it could be turned on as a treatment for patients with chronic pain.

Reference
Suyi Zhang et al. ‘ ̽��ֱ��control of tonic pain by active relief learning.’ eLife (2018). DOI: https://doi.org/10.7554/eLife.31949

Researchers from the UK & Japan have identified how the brain’s natural painkilling system could be used as a possible alternative to opioids for the effective relief of chronic pain, which affects as many as one in three people at some point in their lives.

Pain can actually help us recover by removing our drive to do unnecessary things - in a sense, this can be considered ‘healthy pain’.

Ben Seymour

Penn State

Prescription bottle for Oxycodone tablets and pills on metal table

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Pain in the machine: a Cambridge Shorts film

amb206 — Wed, 02 Nov 2016 08:00:00 +0000

Pain is vital: it is the mechanism that protects us from harming ourselves. If you put your finger into a flame, a signal travels up your nervous system to your brain which tells you to snatch your finger away. This response isn’t as simple as it sounds: the nervous system is complex and involves many areas of the brain.

We’re developing increasingly sophisticated machines to work for us. In the future, robots might live alongside us as companions or carers. If pain is an important part of being human, and often keeps us safe, could we create a robot that feels pain? These ideas are explored by Cambridge researchers Dr Ewan St John Smith and Dr Beth Singler in their 12-minute film Pain in the Machine.

Already we have technologies that respond to distances and touch. A car, for example, can detect and avoid an object; lift doors won’t shut on your fingers. But although this could be seen as a step towards a mechanical nervous system, it isn’t the same as pain. Pain involves emotion. Could we make machines which feel and show emotion – and would we want to?

Unpleasant though it is, pain has sometimes been described as the pinnacle of human consciousness. ̽��ֱ��human capacity for empathy is so great that when a robotics company showed film clips of robots being pushed over and kicked, views responded as if the robots were being bullied and abused. Pain is both felt and perceived.

Movies have imagined robots with their own personalities – sometimes cute but often evil. Perhaps the future will bring robots capable of a full range of emotions. These machines might share not only our capacity for pain but also for joy and excitement.

But what about the ethical implications? A new generation of emotionally-literate robots will, surely, have rights of their own

Pain in the Machine is one of four films made by Cambridge researchers for the 2016 Cambridge Shorts series, funded by Wellcome Trust ISSF. ̽��ֱ��scheme supports early career researchers to make professional quality short films with local artists and filmmakers. Researchers Beth Singler (Faculty of Divinity) and Ewan St John Smith (Department of Pharmacology) collaborated with Colin Ramsay and James Uren of Little Dragon Films.

̽��ֱ��pain we experience as humans has physical and emotional components. Could we develop a machine that feels pain a similar way – and would we want to? ̽��ֱ��first of four Cambridge Shorts looks at the possibilities and challenges.

Pain in the machine

Researchers: Beth Singler and Ewan St John Smith

Still from Pain in the Machine

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Cause of phantom limb pain in amputees, and potential treatment, identified

sc604 — Thu, 27 Oct 2016 10:49:19 +0000

Researchers have discovered that a ‘reorganisation’ of the wiring of the brain is the underlying cause of phantom limb pain, which occurs in the vast majority of individuals who have had limbs amputated, and a potential method of treating it which uses artificial intelligence techniques.

̽��ֱ��researchers, led by a group from Osaka ̽��ֱ�� in Japan in collaboration with the ̽��ֱ�� of Cambridge, used a brain-machine interface to train a group of ten individuals to control a robotic arm with their brains. They found that if a patient tried to control the prosthetic by associating the movement with their missing arm, it increased their pain, but training them to associate the movement of the prosthetic with the unaffected hand decreased their pain.

Their results, reported in the journal Nature Communications, demonstrate that in patients with chronic pain associated with amputation or nerve injury, there are ‘crossed wires’ in the part of the brain associated with sensation and movement, and that by mending that disruption, the pain can be treated. ̽��ֱ��findings could also be applied to those with other forms of chronic pain, including pain due to arthritis.

Approximately 5,000 amputations are carried out in the UK every year, and those with type 1 or type 2 diabetes are at particular risk of needing an amputation. In most cases, individuals who have had a hand or arm amputated, or who have had severe nerve injuries which result in a loss of sensation in their hand, continue to feel the existence of the affected hand as if it were still there. Between 50 and 80 percent of these patients suffer with chronic pain in the ‘phantom’ hand, known as phantom limb pain.

“Even though the hand is gone, people with phantom limb pain still feel like there’s a hand there – it basically feels painful, like a burning or hypersensitive type of pain, and conventional painkillers are ineffective in treating it,” said study co-author Dr Ben Seymour, a neuroscientist based in Cambridge’s Department of Engineering. “We wanted to see if we could come up with an engineering-based treatment as opposed to a drug-based treatment.”

A popular theory of the cause of phantom limb pain is faulty ‘wiring’ of the sensorimotor cortex, the part of the brain that is responsible for processing sensory inputs and executing movements. In other words, there is a mismatch between a movement and the perception of that movement.

In the study, Seymour and his colleagues, led by Takufumi Yanagisawa from Osaka ̽��ֱ��, used a brain-machine interface to decode the neural activity of the mental action needed for a patient to move their ‘phantom’ hand, and then converted the decoded phantom hand movement into that of a robotic neuroprosthetic using artificial intelligence techniques.

“We found that the better their affected side of the brain got at using the robotic arm, the worse their pain got,” said Yanagisawa. “ ̽��ֱ��movement part of the brain is working fine, but they are not getting sensory feedback – there’s a discrepancy there.”

̽��ֱ��researchers then altered their technique to train the ‘wrong’ side of the brain: for example, a patient who was missing their left arm was trained to move the prosthetic arm by decoding movements associated with their right arm, or vice versa. When they were trained in this counter-intuitive technique, the patients found that their pain significantly decreased. As they learned to control the arm in this way, it takes advantage of the plasticity – the ability of the brain to restructure and learn new things – of the sensorimotor cortex, showing a clear link between plasticity and pain.

Although the results are promising, Seymour warns that the effects are temporary, and require a large, expensive piece of medical equipment to be effective. However, he believes that a treatment based on their technique could be available within five to ten years. “Ideally, we’d like to see something that people could have at home, or that they could incorporate with physio treatments,” he said. “But the results demonstrate that combining AI techniques with new technologies is a promising avenue for treating pain, and an important area for future UK-Japan research collaboration.”

Reference:
Takufumi Yanagisawa et al. ‘Induced sensorimotor brain plasticity controls pain in phantom limb patients.’ Nature Communications (2016). DOI: 10.1038/ncomms13209

Researchers have identified the cause of chronic, and currently untreatable, pain in those with amputations and severe nerve damage, as well as a potential treatment which relies on engineering instead of drugs.

We wanted to see if we could come up with an engineering-based treatment as opposed to a drug-based treatment.

Ben Seymour

Osaka ̽��ֱ��

Measurement of brain activity in a patient with phantom limb pain

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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