Smart opioid plaster, neuromodulation, gene therapy, and big data – how pain syndromes are treated nowadays.
In what way HIV may be used to ease the severe pain of the patient, why opioid plasters kill people, how medical startup can find an engineer – these and other issues were discussed by Innovation House with Roman Cregg, MB BS (Hons), FRCA, FFPMRCA, PhD (UCL), and Pain Treatment Expert at University College London Hospitals.
Roman Kregg is the world-class expert in the field of anesthesiology, intensive therapy, and pain medicine. In other words – algiatrist. In the past few decades, this field of activity got extensive development, and in more economically developed countries it was morphed into separate medical specialty – like widely known cardiology, nephrology or traumatology.
Roman was born in Lviv city, Ukraine, where in 1998 he graduated from Danylo Halytsky Lviv National Medical University. The he moved to London, where he has successfully passed all the stages of the British postgraduate education.
His qualification and right to engage in private medical practice were recognized when he was admitted to the Faculty of Pain Medicine of the Royal College of Anaesthetists. Currently Roman holds the position of Consultant Doctor in Pain Medicine and Anaesthesia at the University College London Hospitals (UCLH), Academic Lead (research position) in Pain Medicine at the National Hospital for Neurology and Neurosurgery, and Honorary Senior Clinical Lecturer at the University College Hospital (UCL) Institute of Neurology.
In spite of the fact that for nearly 20 years Roman resides and works in the UK, he did not break the ranks with Ukraine – he arrives on a regular basis and delivers lectures, holds masterclasses. Moreover, Mr. Cregg is the initiator and primary coordinator of the British-Ukrainian Symposium on Anaesthesiology, Intensive Care and Pain Medicine that is annually held in Feofaniya Clinical Hospital in cooperation with the Shupyk National Medical Academy of Postgraduate Education (Professor Oleh Loskutov, Assistant Professor Maxym Pylypenko).
In Ukraine Mr. Cregg is also engaged in implementation of advanced world’s knowledge and approaches in the field of pain relief and pain management into Ukrainian medical practice.
Active public activity of Roman Cregg, as the President at the Ukrainian Medical Association of the United Kingdom is furthering this goal. The UMAUK unites the British doctors and nursing sisters of Ukrainian origin and those, who work at the Ukrainian Institute of Pain Research. The latest project is being performed jointly with the Romodanov Neurosurgery Institute – namely with Vadym Biloshytskyi, Doctor of Medical Sciences, and consists in both transfer of best practices to the Ukrainian doctors during the masterclasses and training courses in advanced practices of pain treatment, and attempts to lay in Ukraine the foundations for the advanced basic researches of such innovative treatments methods of chronic pain as the gene therapy.
– What methods and technologies of pain treatment are considered to be the most future-oriented in the Western world?
– Nearly 20% of the UK people suffer from one or another chronic pain – the one that lasts more than 3-6 months. In other words, if you have appendicitis, this is not the chronic pain, since you will have your surgery and your problem will be solved. In earlier times, surgeons treated it with surgery, therapists – with painkillers. The very need for algiatry specialty has emerged because all these specialists have treated in their own fashion, and there were no single multifaceted approach. There are many literature, scientific papers, but the present-day chronic pain therapy lies in three axes.
The first one is systemic, topical, antineuropathic analgesics. The second is interventions, that is, blockers, administration of steroids into the joints, ligaments, along the nerves, neuroablations, destruction, neuromodulation that will be described below. The third one is psychological support of the patient for him to be able to control himself with no external assistance, to learn to live through the pain, instead of against the pain – to live with pain, acknowledge the pain as the fact of his life.
There are the three pillars of the pain medicine. However, doctor holds no privileged position, many other experts deal with pain treatment too, since this is a social problem, rather than solely medical one. Field-specific doctor determines the management and optimizes the problem, while the general practitioners and physiatrists deal with rehabilitation. In other words, this is multidisciplinary medicine, since many specialties are involved.
Advanced pain treatment technologies
– Let’s talk in greater detail about innovative pain treatment methods. What advantage may experts in this field benefit from advanced technologies?
– New technologies emerge from three various sources. The first one is medication, namely new pharmaceuticals. The second one is engineering, namely emergence of new devices for medical use. And the third one is scientific innovations, where pharmaceutical industry is also partially involved, but this is about gene therapy, stem cells that are being implemented even now.
Nowadays medication is neglected in pain medicine, since it has no evidence-based support. That is to say that therapeutic painkillers – paracetamol, ibuprofen, opioids – are fewer and fewer used to treat pain. That’s why there is no great practical point for us in cooperation with pharmaceutical industry – almost all pharmaceuticals turn out to be ineffective.
Nowadays medication is neglected in pain medicine, since it has no evidence-based support
– So, pain pills are the thing of the past already?
– Yes, they are, and opioids too. If no new classes of painkillers are discovered, then we have, for instance, the potential to use the properties of alcohol, but without the dependence. Nowadays alcohol is being studied as the alternative – not in terms of intoxication, but as the blocker of sodium channels that are in charge of pain sensation.
– And what about the second “pillar” – advanced technologies?
– When it comes to advanced treatment tools, neuromodulation plays the dominating role in pain treatment. Its principle is quite simple. If you injured your knee and rubbed it – pain is eased. Neuromodulation works in the same manner. Imagine you have internet and hundreds of internet data traffic units – service quality will drop. Internet channel capacity is 100 units. Let’s suppose that this channel is used by two persons, each of them need 70 units, so the general demand is 140? Channel cannot allow them to watch the movie simultaneously – the image will be slurred. The same happens with pain and rubbing. These are two different, but integrated “channels”. If I hit my elbow, then 80% of “data traffic” are loaded with pain. Pain is severe. But if I start rubbing the place I hit before, then I overload the channel by 30-40%. So, basically, the pain decreases, when I overload two channels.
Nowadays alcohol is being studied as the alternative – not in terms of intoxication, but as the blocker of sodium channels that are in charge of pain sensation
Electric stimuli at the spinal cord level make the neural pathways transmit the feeling of touch, or rather the rubbing, but not the feeling of pain.This is effective. In this case, person needs no opioids. The pain is treated when we load relevant channel with the huge stream of data. This is a great innovation, it has revolutionized the pain treatment.
– And what about surgical treatment methods? Were they changed?
– This field has its innovations too, but, for better or worse, currently surgery is as unpopular for pain treatment, just like the pharmacological therapy. The surgeries cannot improve for a long time the state of patients suffering from the chronic pain. On the other hand, neuromodulation can improve the patient’s condition for 5 to 10 years. As of today, neuromodulation is about 50% of all the pain medicine.
– In a positive way. The neurostimulation has no side effects of systemic analgesics. Diclofenac or opioids are dangerous pharmaceuticals. Surgery is dangerous in itself. Therefore, neuromodulation is a major progress.
Smart plaster, health-friendly x-ray, and gene therapy
– Could you please be so kind to tell me about your developments.
– Now we have standard therapy of acute pain, – that occurs due to cancer, for instance, – application plaster. It has micropores, that every hour release certain number of molecules into the blood of the patient. You apply it to skin and get rather long and stable – for several days – dose of opiate. The advantage of the plaster is that throughout the day and night the patients receive the very same dose that the pills have.
But this is also a problem at the same time. None of the physiological systems in the body works in a standard and stable way – you don’t need the same amount of pharmaceutical, as you have it at night, in the evening or after meals. Usual plaster contains a standard dose. If you have kidney failure and take a bath, you may die, since the dose increases manifold as the temperature goes up. For this very reason thousands die in the USA every year. This is a dangerous therapy in case of a dangerous disease.
None of the physiological systems in the body works in a standard and stable way
Our team is working on the creation of “smart” microchip plaster that will know when to give bigger or lesser amount of pharmaceutical. We want the painkillers administration process to be physiological. The name of the project will be an abbreviation that will mean “Intelligence in the field of painkillers administration”. At this stage, we are dealing with the prototype – it costs about $10,000, but it will be rather cheap when the large-scale manufacturing is launched.
– Who is working on the development?
– Our pharmacologist is at work on molecules that will be included in the plaster, – we shall decide what synthetic opioid will be used.
I give the clinical studies. We take 20 to 40 patients suffering from the same problem and study the regularities – how acute is the pain of the patient from one or another activity type, – in view of this we are creating the algorithm that will then be used in the chip. Moreover, the patient will be able to control the dose of the pharmaceutical by himself.
Engineers in South Korea also work with us. They deal with technological issues of our “smart” plaster development. In the best-case scenario, in 7 to 8 years it is likely that product will enter the market.
– How can doctor or scientist find engineers able to turn their project or idea into reality? Tell me, please, how did you find your South Korean partners.
– This is a very interesting question. The first thing I started to do is reading the patents. You shall look for the team dealing with what you are interested in, the one that may resolve your problem. I had the clinical endpoint. I had to find the engineer. So, I opened the engineering database, started to monitor the patent database. I found two or three teams, who have already patented what I was looking for, and opened the dialogue with them. Then it turned out that I need the third constituent – pharmaceutical expertise. This is my story.
The first thing I started to do is reading the patents. You shall look for the team dealing with what you are interested in, the one that may resolve your problem.
– I know that you are also engaged in educational project for doctors…
– Our second project relates to the danger, caused by x-ray. Both patient and doctors, who work with him in surgery room, are exposed to harmful radiation. Less experienced doctor spends much time to find the place suitable for the invasion. To reduce this time, I and my team of developers are creating the special training simulator – X-Sim. We are building the training station that emits no radiation. We are collecting the huge database of x-ray pictures. This simulator will allow young specialists to learn how to find the right place on the patient’s body within the shortest possible time.
– What is the third direction of your innovative activity?
– This is the gene therapy. We want to use it for chronic pain treatment. Pain on its own is the very simple signal. This is the closing and opening frequency of sodium channels. When someone strokes you, then the frequency is low. If you are cut with a knife or if you have burning sensation, then this frequency will be very high. However, we may hold down the ability of these channels to open and to close. We will actually transform the pain into the feeling of touch.
We use so-called “vector” – retrovirus of HIV, for instance – do deactivate the channels and to scale down the amount of pain felt by the person. It shall bear genetic information that will help to slow down closing and opening processes of sodium channels. The main task of the virus is to change the DNA of the cell, into which it was “intruded”. In our situation, instead of infecting the cell with HIV-information, we “infect” it with completely different material – useful one. Sure thing, by doing so, we check and deactivate the virus. Harmful part of live virus may be extracted.
Instead of infecting the cell with HIV-information, we “infect” it with completely different material – useful one
Future-oriented and experimental methods
– What are the current experimental methods of pain treatment in the Western world?
– There are developments that reach the clinic. We have innovations, and this is not about pharmaceuticals only. There are two sides of the medical industry: efficiency and safety. When you walk down the street and enter the hospital, the risk of your death is increased by 15%, since the hospital is a dangerous place. You may find there toxic substances, pharmaceuticals, x-ray machine, lots of dangerous equipment. Medical malpractice exists too. But the are many innovations too, and they resolve these problems. Important task is to avoid death.
Imagine that four people having pneumonia were admitted to hospital. They will have their blood examined, they will make x-rays. They will have similar clinical findings, but some of them are healthier than others, someone is smoker, older or younger – they all have different chances to be recovered. And what if we take 100,000 persons or 200,000? Google has already purchased huge databases of patients, who admitted to hospitals, and is trying to analyze these data to develop the algorithm that may avoid death, having foreknowledge of what person is more likely to die.
The second important medical project – augmented reality. In other words, when I see x-ray picture, artificial intelligence tells me that there is incomprehensible zone, cancer may be there. The system will immediately offer me the best recommended intervention. The possible use of augmented reality during the surgeries is widely discussed in precisely this way.