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We welcome L. Joseph Parker, a research physician, as we delve into a study that explores the potential of low-frequency ultrasound waves in pain management. Joseph will guide us through the intriguing findings of this study, shedding light on how targeted ultrasound stimulation of the insula region of the brain offers promising relief from pain perception. We’ll discuss the significance of neural responses, safety considerations, and the ethical implications of this innovative technology.

L. Joseph Parker is a research physician.

He discusses the KevinMD article, “Ultrasound shows promise as new pain treatment, targeting a specific brain region.”

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Transcript

Kevin Pho: Hi, and welcome to the show. Subscribe at KevinMD.com/podcast, and get CME for this episode by clicking on the CME link in the show notes. We welcome back L. Joseph Parker. He’s a research physician and regular guest on the podcast. Today’s KevinMD article is “Ultrasound shows promise as new pain treatment, targeting a specific brain region.” Joseph, welcome back to the show.

L. Joseph Parker: Thank you very much.

Kevin Pho: So Joseph has been on multiple times. Go to KevinMD.com/podcast to search for his prior episodes and hear his story. Today’s KevinMD article talks about low-frequency ultrasound as a modality for pain relief. Tell us what this article is about.

L. Joseph Parker: Well, as I’m sure everyone’s aware, doctors are frantically searching for some way to treat severe chronic pain that does not involve opiates. Not because opiates don’t work, but because they’re not politically popular right now. And so we’re searching for some way to help ease the suffering of these patients.

Ultrasound for altering activity is something that’s fairly new to me, but not new to the scientific community. It was even, I think, back in the 1950s that the first experiments started, and as far back as 2008, so 16 years ago, they were making some very good progress in being able to focus these ultrasounds using destructive and constructive interference so that they could affect just a few millimeters of target tissue. I had no idea that they had been able to develop that type of precision.

Then they can use either low intensity or high intensity to either affect neuronal activity or to actually ablate tissue. They can destroy tissue, they can target tumors with ultrasound now, brain tumors through the skull.

Kevin Pho: So tell us the study, or the news article, that brought this technology and its association with pain relief to your attention.

L. Joseph Parker: Sure. So when we’re talking about acute pain or chronic pain, the acute pain starts in the peripheral tissues, goes through the peripheral nerves to the spinal cord, usually by sodium channel mediation, and then up through the spinal cord by neurons that are predominantly affected by calcium channel mediation, and then up to the thalamus, and from the thalamus to awareness, which is cortical activity, which in this case is the insula.

The insula is a small area of the brain that is tucked away under the frontal, temporal, and parietal lobes, and to see it you actually have to move extensions of those lobes that are covering over the insula. They’re called the opercula. And when you move those away, you see an island, which is what insula means, of brain tissue. That is where we become consciously aware of pain.

So in this study they wanted to use low-intensity ultrasound to suppress activity in either the posterior insula or the anterior insula and see what effect that had on pain. And they did a beautiful study.

Measuring pain is almost impossible for physicians to do. We ask the patient, on a scale of zero to 10. People who’ve never had much pain at all, they might think that falling and skinning their knee is an eight. People who have had multiple failed back surgeries and are in severe chronic pain, they might rate that as a two, and of course they’re living in a nine every day and they call it a five because it’s their average day.

So what they did instead was they used heat applied to the hand, and then recorded the EEG response in the brain to that heat. And studies have shown that this is a pretty accurate measure of the perception of pain, of how much pain is being generated through all those connections up to the brain. So when it gets to the brain and it scores a five, which is what they go for, then they know that they’ve got a standardized pain stimulus. Then they can apply the ultrasound to these different areas of the brain and see if that dampens that stimulus. So, really a very well thought out, very beautiful study.

Kevin Pho: So give us the results of that study in terms of the efficacy of this modality.

L. Joseph Parker: So they found that these low-intensity focused ultrasound waves, when they would hit the anterior or posterior insula, would reduce the person’s perception of pain by a statistically significant amount. So the pain signal is still there, you just don’t care about it as much, because the part of your cortex dedicated to caring about pain is being suppressed.

We know this is possible because if your doorbell rang and you were walking across the floor and you stepped on a thumbtack, it would hurt terribly and you would go hobbling over to the door angry. If you open it up and it’s someone with a big check and you’ve just won a million dollars, that pain would instantly shut off. But we don’t have conscious control of that ability. This is the part of the brain that does influence that.

So it is possible that modalities like this could be used even in the emergency room, so that when someone comes in, a device could be placed against the skull and turned on. Most pain treatments in the emergency room, morphine, or if you give someone a little Versed, they still feel the pain, they just tell you it doesn’t hurt as much, or it’s at a distance. And this sort of does the same thing. It’s preventing the cortex from responding to and making your conscious mind focus on that pain. So if it were possible to use this in the emergency room, and perhaps even home-based therapy, if long-term use doesn’t cause any issues.

So these sound waves are going through, and there are voltage-gated ion channels and there are also mechanically gated ion channels that respond to this movement, and these channels will open and either calcium will go through, or chloride will come out, potassium will come out. They can hyperpolarize or depolarize a neuron through these ion channels, and these waves seem to be affecting those ion channels and not causing any significant damage to the tissue.

And they’ve studied this for a long time, and they can cause tissue damage when they want to, if they’re targeting an area of the brain that is causing a movement disorder. So they’ve treated some movement disorders by focusing on and ablating a small area.

I had been looking a lot at transcranial magnetic stimulation and using magnetic fields for this purpose, but then this article came out and I had gone back to research what has been learned since I was in medical school and learning about this, and they have made tremendous progress in this area. So there’s the potential to help people suffering from severe chronic pain by using these devices.

That doesn’t mean that any sound placed against your skull, a speaker placed on your skull, will make a difference, or that even any ultrasound will make a difference. These are extremely tuned to produce a specific cone of effect, and it’s very precise mathematics that goes into creating this. I don’t know how they adjust it for the different skull sizes and all that, but they do.

So right now this is in the laboratory. It’s been proven to be statistically significant, and this could be a very interesting intervention if this can be mated with some type of AI control system, where it could send a scanning wave to find the needed area to affect and then send an affecting wave to produce the kind of inhibitory effects on that area of cortex.

Kevin Pho: Now, I know that this is in the investigational stage, but as far as you know, are there any detrimental or adverse effects from low-intensity ultrasound to the skull?

L. Joseph Parker: Well, what they did was they looked at the high-intensity ultrasound to see what effects it was having, how it was destroying tissue, and it does it through three main modalities.

One is through temperature differentials. It’s generating some heat in there. Vibration, heat is vibration, so by increasing the vibration you increase the heat. The other way is by cavitation, so the sound waves are creating pockets of gas that then collapse and generate an almost explosive, light-like force. And then there’s just mechanical shearing, where you’re shaking a neuron enough that it tears and damages the cell membrane, or just the membrane of any cell.

So then they backed away from those, and the low-intensity focused ultrasound does not shift the temperature more than one degree Celsius. It does not cause any movement significant enough to cause any shearing or damage to the cell membranes. And these sensitive ion channels respond to it, but almost nothing else does. So so far it has proven to be extremely benign.

Kevin Pho: Now, again, I understand that this is in the investigational stage. Are there any specific types of pain that would respond better to ultrasound versus other types of pain?

L. Joseph Parker: Amazingly, this should work on all types of pain, because this is going all the way up to the end area where we become consciously aware of and focused on our pain.

So when pain signals come up from the body, they demand our attention and our focus. They make it very hard for us to sleep, very hard for us to concentrate on anything else, because our body is saying something is being injured, you must stop that injury. A person with an amputated leg, it’ll feel exactly like their leg is in a fire, and the brain is continually telling them, escape that pain, fix that problem. Of course they can’t, and so they’re stuck with this constant signal keeping them awake, not letting them focus, occupying almost every waking thought.

By suppressing this area of the brain that processes pain, and is sort of the area that then grabs the frontal lobes’ executive function and says pay attention to this, if that area can’t send those signals, then the pain is still there but it’s at a distance, and we can go on and live our lives.

This area of the brain is also, however, instrumental in empathy and mirror neurons and being able to process and respond to the feelings of others. So if a device were constantly focused on this, there might be some personality changes. This is speculation, of course, and someone might be less empathetic. On the other hand, being in constant pain also causes some pretty significant personality changes. So you would have to see if the improvement was much better than the untreated pain, which is often ignored in a lot of studies.

You see a lot of studies with opiate medications where they compare people on higher dose opiates with people on lower dose opiates and say the people on the higher dose opiates have a lower life expectancy. But they completely ignore the fact that these people are on the higher opiates because they’re suffering more intense pain, and the experience of pain, the lack of sleep, the effect on your social environment, damages your life and shortens your life expectancy too. Depression shortens your life expectancy. If you’re hurting all the time, it’s hard not to be depressed.

So perhaps a device like this could be used, say, at sleep time. So you go to bed, the device is turned on, and it would suppress your mind’s ability to focus on that pain and allow you to get a good night’s rest. Because that’s one of the things that chronic pain sufferers invariably have a tremendous amount of trouble with, is just getting adequate sleep. And without restorative sleep, if you can’t drop down into those delta waves and theta waves and the other things that are necessary to survival, we know lack of sleep will kill you. Fatal familial insomnia is invariably fatal. Yet we often don’t understand, if we don’t suffer from these problems, how horrible it is not to get a good night’s sleep. So perhaps this device could aid with that.

Kevin Pho: So what do you see as the path forward in terms of the next step for this particular modality?

L. Joseph Parker: Since this has been determined to be a benign modality and a benign way to affect cortical processing and to inhibit cortical processing, I think that the next study that someone should do would be a sleep study, and then you can study the brain wave patterns. So you record a baseline brain wave pattern in these patients, say every night for a week, and see what their sleep quality is. We have sleep labs all over the country dedicated to that, for sleep apnea and other things that we know interfere with quality sleep. Then you could put this device on, turn it on, let it run overnight, and see if they’re getting higher quality sleep.

If they are, this could be critical, because when you have severe chronic pain and you’re on a pain treatment medication, even something like gabapentin, adding something to help you sleep is often perceived as dangerous, and it does complicate things. Even something as simple as Benadryl in a Tylenol PM can act synergistically with the gabapentin you’re on and can suppress your respiratory drive, and of course that’s what we’re hoping to avoid in these new treatments and modalities. So combining a benzodiazepine, or of course a barbiturate, or even something as mild as Lunesta or something like that, that would be fine with someone who’s not on chronic pain therapy. There’s a big risk benefit analysis you have to do before you treat with those two medications.

And this device could obviate that need, could allow people to get a good night’s sleep through non-pharmaceutical means. They could still have their daily pain treatment while they’re awake and then be safer at night.

Kevin Pho: We’re talking to L. Joseph Parker. He’s a research physician. Today’s KevinMD article is “Ultrasound shows promise as new pain treatment, targeting a specific brain region.” Joseph, as always, we’ll end with some of your take-home messages to the KevinMD audience.

L. Joseph Parker: The treatment of severe chronic pain is an extremely complicated issue. Every patient will have very individualistic issues and problems, and they really have almost their own diagnosis because of how complex this issue is. So each individual patient will need to be treated as an individual.

If this works in some people and not in others, I sincerely hope they don’t mandate its use and act like it’s a panacea for everything, when for some people it will work effectively and for others it will not. At the same time, don’t deny its use because it only works in a subset.

And understand that these patients need something to help them. Without some sort of help or intervention, they live very short and terrible, miserable lives.

Kevin Pho: Joseph, once again, thank you so much for sharing your perspective and insight, and thanks again for coming back on the show.

L. Joseph Parker: Thank you, Dr. Pho.