Krishnan Chakravarthy, M.D., Ph.D., Assistant Clinical Professor of Anesthesiology and Pain Medicine at UC San Diego Health and VA San Diego Healthcare talks about a Bluetooth device that aids in pain relief.
Interview conducted by Ivanhoe Broadcast News in February 2019.
It’s almost miraculous with how this Bluetooth device attacks pain and makes it go away. Can you describe how it works?
Krishnan: Spinal cord stimulation historically has been around for 50 years since the first implant in 1967. Interestingly, the story started in the late 60s by a neurosurgeon by the name Norman Shealy. What he observed was that based on two scientists that thought about putting electricity in the spinal cord, electricity in small amounts can modulate pain from all the way from your peripheral nervous system to your central nervous system through upregulation of inhibitory neurotransmitters. He thought about this idea that was originally in pain medicine, and what we call the Wall and Melzack Gate Control Theory. This theory is this idea that the body regulates flow of pain information through the spinal cord and by exposing the spinal cord to small amounts of electrical current there is increased activity of inhibitory inter-neurons that reduce pain transmission to and from the brain. He actually placed the first subdural lead in a palliative patient. So that spurned over the course of the last 40 to 50 years a revolution in the concept of using current in the spinal cord and the brain to get this desired effect on pain control. Fast forward to about 10 years ago, industry never really thought about spinal cord stimulation as a growing market till a couple companies out of the San Francisco Bay Area started developing what we called sub-perception stimulation. The idea of sub-perception stimulation is even though you’re putting current in the spinal cord, where originally patients used to feel this tingling sensation in the area that they were getting stimulated they no longer felt this effect. Clinician and industry partnerships have now started advancing the science of stimulation to the point that now different waveforms that we use in terms of viewing electricity as a dose has resulted in patients not even feeling that effect and getting the same effect with less energy usage. Now, the technology which Raul has gotten significant benefit from is due to us understanding what different parts of the spinal cord do in terms of pain control. With dorsal root ganglion stimulation we’re directing that current to being more localized to the nerve root as opposed to the dorsal column where traditional spinal cord stimulation has been used. That’s really where medical pharmacology in its entirety is, its’ about finding ways to achieve a desired effect with a minimal amount of therapeutic dose. The analogy I give is you don’t go to your primary care physician asking for 200 milligrams of a blood pressure pill if you can get it done in 25 milligrams. His therapy is really the first attempt at targeting a unique root within the spinal cord to affect pain with less energy due to localizing the leads directly at the target site as opposed to stimulating a larger segment of the spinal cord. This means longer battery life, lower energy placed on the cord, and likely better long-term patient outcomes.
How does that work?
Krishnan: This is probably the toughest question because as clinician scientists that are researching phantom limb pain we are still trying to understand why someone who has an injury, and that injury has resolved, still continues to have pain, as in this case with Raul. In his case, it’s even more unique because the limb that he’s experiencing pain doesn’t actually physically exist post amputation. It’s been a medical puzzle in terms of trying to figure out what happens in these patients. At this point the science is at the hypothesis stage without clear mechanistic evidence. One part of it is that like most chronic pain patients, pain isn’t supposed to be long lasting, but teleologically if you look at evolution, pain is your most fundamental defense mechanism, whether it’s an emotional component, or whether it’s through a form of acute injury. But for Raul, it’s possible that part of his brain has rewired. His brain hasn’t really understood that the events that caused the acute pain event have resolved. Some in the medical community define this as central sensitization. One could say that it’s really something happening at the site of injury, but there’s more growing evidence that it’s really something that happens in the brain where it rewires thinking that that injury’s still happening when it’s not. For him, it’s been almost 18 years, and that’s really, really tough because it’s not just affected the fact that he’s handicapped from the initial injury, but that the pain has really permeated his whole life in terms of his social dynamics, his relationships and just the limitation of what you can do day in and day out.
And this is true pain relief. There’s not a psychological, your brain’s turning it off because you think you’re getting medicine. This is actually making it go away.
Krishnan: That’s a great question. University of California San Diego (UCSD) has always been a very interesting institution in pioneering medical advancements. One of the actual other major therapies that came out of UCSD for phantom limb pain was mirror therapy, which is this idea that when your looking into a mirror your brain is wired to program the contralateral side. So if your brain sees that the injured limb in the mirror looks ok and works normally it may result in tricking your brain into assuming your phantom limb is healthy and hopefully results in some rewiring. The contra-lateral image in the mirror can tell you that it’s actually non-injured as a way to get your brain to thinking that the process of injury is over and to become less sensitized. In our case with how we see dorsal root ganglion (DRG) stimulation therapy working is that the pain transmission pathway starts at the distal phantom limb and goes all the way to your brain through your spinal cord. A common analogy I use with my patients is that if you have a 16-lane highway of a bunch of cars that are driving, we’re effectively setting a roadblock across that highway, the stimulation sets up the roadblock. In our case the roadblock is at one of the points of convergence in the neuronal highway starting at the distal limb working its way towards to brain via the dorsal nerve root. There is unarguable evidence in terms of both science as well as folks who use DRG stimulation that it’s a very effective therapy not just for phantom limb pain but potentially any focal neuropathic pain.
Is it still the trial phase?
Krishnan: No it’s not. Actually, the therapy is no longer in its trial phase. It’s FDA approved. It has been launched nationwide. The indications for DRG therapy right now are mainly Complex regional pain syndrome (CRPS) type 1 and Type 2. But obviously, given that CRPS shares the same pathogenesis as some of the other neuropathic pain diagnoses the therapy can be extended to these indications. Interestingly, increasing evidence supports that DRG therapy may also be working by affecting the neuroimmune axis and depressing inflammation. Given a lot of chronic pain get worse and is through some kind of chronic immune effect, DRG therapy suppressing inflammation may be another way this therapy works. So DRG therapy is really being applied to things like pelvic pain for women, vascular pain, groin pain as examples in addition to phantom limb pain. But really the applications can be much broader, and we’re just scratching the surface.
When was the FDA approval?
Krishnan: Two years ago DRG therapy got FDA approval. The patients control the therapy themselves. I mean it’s a very easy setup. This is where technology has really changed the way for increased patient compliance. Patients have their own remote control that they can adjust the therapy. They have access to someone who we call a device representative. So independent of the clinician, once the trial and implant is done, the device rep is pretty much accessible to all these patients 24/7. So if there’s a question about how should I feel or not feel this effect they are there to answer these questions in addition to the clinician. Patients get constant feedback. Compared to historic devices now the batteries themselves have really come a long way. Patients can elect to have both rechargeable as well as non-rechargeable or primary cell batteries. These batteries can last approximately 10 years after implant before they need replacement. So it’s almost like buying a new wireless pacemaker for the spine to achieve pain control. Expense is an issue in terms of international market growth. Some of the big questions facing pain medicine is in a fantastic therapy like this with good outcomes, how do we ever see it in the developing countries when the cost of a device like this is in the range of 25 to 40 thousand dollars? And insurance covers that cost in the US, but for a lot of the developing countries that’s not the case. So there’s going to be a time where I think industry in partnership with clinicians is going to have to really realize the value of trying to bring this type of therapy to the more common public for broader consumption both nationally and internationally. I think the one piece that makes dorsal root ganglion stimulation really different than spinal cord stimulation, which is just placing two leads in the dorsal column, is unilateral pain which means that patients that have pain that’s localized to one side of their body that isn’t on both sides or it’s not affecting both sides. These patients would most benefit from DRG therapy over traditional dorsal column stimulation. So localization of your pain makes it easier to target it at the dorsal root level than to put it directly in the spinal cord to minimize the energy required to achieve pain control.
What is it you’re placing inside the body and where do you put it.
Krishnan: Sure. So when you look at most patients, there is this idea that goes back to the analogy of the highway. So the spinal cord is very beautifully organized where different highways overlap in different parts of your body, what we called dermatomes. So a single dermatome can cover certain parts of your lower back as well as other parts of your leg versus another dermatome that can cover your neck area and parts of your shoulder and your hands and fingers. Its like a long nerve highway coming from your back to your foot. So for Raul, his pain really was one part from the incision site following amputation surgery that he had that was localized to one dermatome and the other part was where the actual limb that doesn’t exist is still causing him pain, phantom limb. So by placing it in the dorsal nerve roots that cover these dermatomes we were able to get rid of his pain. So when you look at those dermatomes which are just kind of medical jargon for localized highways where the spinal cord senses and can controls motor function, putting leads at the dorsal root and stimulating at certain amplitude and frequencies prevents pain to that area without affecting the sensation or motor function to that dermatome and to rest of the body.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Yadira Galindo
858-249-0423
Sign up for a free weekly e-mail on Medical Breakthroughs called First to Know by clicking here.
