Deep Brain Stimulation for Chronic Pain

Prof. Konstantin Slavin

Professor & Head of Section of Stereotactic and Functional Neurosurgery, University of Illinois

Professor Konstantin Slavin is a neurosurgeon in Chicago, born and raised in the Soviet Union, where he attended medical school in his hometown of Baku in Azerbaijan. He had his residency in Moscow and then moved to the United States where he had another residency in Chicago. He has been in the University of Illinois for many years as he started his practice there in 2001 and has been doing it ever since. He does a lot of neurosurgical interventions but his specialty is functional and stereotactic neurosurgery. He is focused on conditions that are considered functional neurosurgical issues, those include chronic pain, movement disorders, epilepsy, psychiatric conditions. Prof. Slavin has been involved in a variety of neurosurgical and professional societies and he was the president of the American Society of Stereotactic Functional Neurosurgery. Currently, he is the president of the International Neuromodulation Society.

What are functional disorders?

When you talk about something being functional, people immediately assume that it may be psychogenic or completely non-existent or an example of malingering. Realistically functional disorders have been set aside in the past because of relatively normal anatomical issues, so there was no organic substrate for either pain or movement disorders, psychiatric conditions or epilepsy and that’s why it was all grouped into this functional disorder category. Functional neurosurgery is essentially improving the function. We now know that all of these conditions, be that chronic pain, Parkinson’s disease, epilepsy or even psychiatric conditions, do have substrate, it may not be organic in terms of anatomical abnormalities, but there are neurochemical disturbances. There are some networks in the brain that are out of control and there are a lot of neurotransmitter changes that happen at different stages of the disease and therefore the interventions make sense because we are really trying to normalize the circuitry of the brain. We are trying to eliminate the symptoms and perhaps the source of those issues in the nervous system. That’s why neurosurgery for functional disorders does make sense

Why do we need invasive approaches for the treatment of pain?

I’m very much convinced that ultimately all the surgical interventions for the treatment of chronic pain will be eventually abandoned and substituted with non-invasive treatments. I’m sure a hundred years from now people will look at us and say “Can you imagine these people were actually implanting something into the human body to control the pain? Perhaps creating even more pain just by introducing some tools into the body to suppress something which can be controlled from outside.” Right now we’re not there yet, as a matter of fact, the non-invasive treatment is something we try first and if it doesn’t work only then we progress to invasive procedures and interventions.

There’s a significant need for effective and safe approaches for chronic pain, particularly for refractory cases that have already failed medications, non-invasive treatments, therapy and so forth. So there is plenty of room for surgery for pain and what we use now are implanted stimulators, peripheral nerve stimulators, spinal cord stimulators, motor cortex stimulators and brain stimulators. They are all examples of how we are trying to affect the pain through electrical signals including devices that can either normalize the conductance of information or perhaps suppress some of the pathways that transmit painful signals. Those are the things that stimulators do.

Interestingly enough, spinal cord stimulation is pretty much the standard of care used widely worldwide for a variety of different indications. The motor cortex stimulation is very far from that and it’s very rarely used for specific indications and almost nowhere in the world that I know of is this particular modality fully approved on a regulatory level. Deep Brain Stimulation is actually a very fascinating story. because pain was probably the second application of it. The first was psychiatry, the second was pain, then came movement disorders, where it became standard and it’s safe and effective. In pain on the other hand it did not turn out to be as effective, even though it was quite safe, and therefore it was almost completely abandoned just maybe 20 years ago.

Now we see some resurrection or renaissance of interest towards Deep Brain Stimulation for pain because there are some specific indications when this could be extremely successful. There are some cases of cluster headaches where we stimulate the hypothalamic area with Deep Brain Stimulation. There are definite diffused neuropathic or nociceptive pains that may respond to stimulation of very specific centres in the brain and that’s something that is the subject of investigations. Now the lack of regulatory approval makes it somewhat challenging to get things going because when there’s no regulatory approval there’s usually no insurance coverage so we have to find some pathways for patients to get this modality and then there should be some ongoing research in terms of data collection analysis trying to find the best candidates for this and maybe try to find the ideal target for certain indications. That is a work in progress.

What is cingulotomy and how can it be used to treat patients suffering from pain?

Interestingly enough the majority of our current neuromodulation procedures at the brain stemmed from our past experience with destructive surgery so there is a long history of what’s called cingulotomy, a procedure where there’s very selective destruction of the cingulum and cingulate gyrus usually done on both sides for treatment of a variety of effective conditions. It’s been used for the treatment of depression, obsessive-compulsive disorder, chronic pain and particularly the most refractory cases. In these, patients are so disabled and the pain is so diffused that really nothing else worked for them and cingulotomy did definitely relieve this effective part which is not just an overlay of pain, it’s a big component of the pain perception.

In general, pain has two major components, the somatic which tells you where it hurts and the effective which is a negative connotation of pain, i.e. all this discomfort and emotional overlay that people experience which is definitely regulated and probably centred in the limbic system where cingulum is a big part of. This is definitely a target for our interventions and if we can control this by Deep Brain Stimulation, which is a non-destructive option, then it will definitely be very attractive. It’s hard to say who are the best candidates for that and how universally successful this approach will be, but this is one of those directions which are being investigated now and maybe will present with yet another option for otherwise hopeless patients.

What are the biggest impediments in treating pain with neuromodulation?

There are several. Just the fact that we’re dealing with quality of life probably makes it a little bit less urgent, because you compete with life-saving issues, like trying to cure cancer or control the pandemics which are really life or death types of issues. However, the function is important and I think living longer but miserable is probably not a good way to go. So I think we should concentrate on making people’s life more enjoyable and getting rid of chronic diseases that result in severe pain or the pain itself. It is definitely a noble goal. The rest has to do with the invasiveness of our interventions and our attempts to make it safer and more palatable for patients because imagine if somebody told you that you need to have hole drills in your head and wires sticking there, it’s probably distractive for some but at the same time if it’s effective and it’s safe then perhaps that may be the way to go. So lower invasiveness of interventions will be playing a role here.

We haven’t really touched upon the high cost of devices, but those are probably going to be justified in many ways plus there’s a lot of push towards more affordable new remediation technology so that probably will make things somewhat easier. Then there’s just significant interest and pressure from the patients, who are demanding to have something that will work for them. I think once it gets to the people who distribute resources and create funding for this type of intervention then things will be easier.

How much of an obstacle to progress is the high cost of neuromodulatory hardware?

I definitely foresee the time when the devices will be turning off and on by themselves based on the underlying activity and the settings will be adjusted based on the patient’s condition with either sensors or smart algorithms that will adjust things by themselves. That inevitably will drive up the cost because these things will be more complex but at the same time, I’m pretty sure that not every person needs every feature available. So I think there is some room for simpler devices that can be used as a stepping stone, as an introductory tool, and then based on the patient’s specific needs that simple device can be either upgraded or changed to something more complex if it is definitely beneficial. I’m a strong believer that there will be some very simple introductory tools that will be used for screening patients and then they will be upgraded if needed.

Leaving that aside, I think that the cost-effectiveness of neurosurgical interventions for the treatment of functional conditions has been shown over and over again that, even if it is considered expensive, the price pretty much balances out within a year or two because of reduction in medication use, in emergency room visits, in the care that the patient receives, even in lost work time that gets recouped by controlling the symptoms. Therefore I think the high cost may be destructive at some point, but someone has to look at the bigger picture and understand that this is definitely a cost-effective intervention. From that point of view, I think there’s quite a bit of understanding among decision-making faults and this has not really been an issue. However, there is obviously a concern that not everybody can afford it in the first place.

There’s a certain difference between different parts of the world where neuromodulation has become standard and where neuromodulation is still very much unaffordable. That hopefully will change as well and there will be some equalization in terms of the access to these modalities and perhaps we’ll have different sets of pricing for different parts of the world, based on their ability to pay.

That being said, I don’t want to dwell on the cost of it because I think science should be focusing on something that’s more effective and safer and this should be the driver of our innovation.

What will neuromodulation be like in the future?

Jonathan: If things happen as you predicted and ultimately everything will become non-invasive and externally delivered then it’s also interesting to consider whether or not we’ll actually converge to a standard architecture that’s used for every single disease and the thing that varies is actually the software. So every condition would be treated with the same neuromodulatory “USB” as it were and just the software that you would load onto it would determine what the treatment is. Obviously, that’s slightly a sci-fi application but I think one of the really interesting longer-term possibilities.

Konstantin: I think it’s a long reach goal and I’m pretty safe in terms of my career and even my trainees I think there’s plenty of work for us in terms of interventions and invasive treatment but ultimately yes I think there will be some way to modify the neural activity without implants and whether or not it’s gonna be software or there’s going to be some way to change things in a positive way without intervention at all or just by some chemical neuromodulation, this is something we have to see. The nest is evolving rapidly and I think it will most likely be something that we cannot think of right now, be that chemical or genetic or something else that that just doesn’t come to mind yet. There are many that fascinate me now, for example, reservable devices that you put in for some time and then the device just resorbs and disappears so you don’t have to worry about taking it out or worrying about long-term effects. Something else could be a device that gets powered up by the person’s own heat so you don’t have to worry about battery and charging. We make heat all the time, we have metabolic processes that create temperature and those things can power up our implants. There are a lot of biomarkers that we are not aware of yet or maybe we know them but we don’t know how to use them for something that will allow us to gauge the treatment or maybe modify it. This is something that will probably be driving functional neurosurgery among other fields in the future.

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