Okay, so now we have a neurosurgical face-off. The topic is going to be, sorry, on pain procedures, and Dr. Ashwin Vishwanathan is going to give the neuromodulation for pain side. The two contestants have been apprised of the ground rules. All right. Well, thanks very much. I appreciate the opportunity to share. And, you know, so hopefully over the course of the next eight or ten minutes, I'll share with you why neuromodulation of pain is really where the future is and where our treatment should be today. I don't have any relevant disclosures. I would say, though, you know, I really do believe in ablation as a treatment option, but there are a lot of exciting things for neuromodulation. So, you know, I'll start off by saying that destructive procedures have no role in the management of nonmalignant pain. And, you know, I think this is probably a true statement. You know, Dr. Bertschl, I can't remember what year this is now, 2009, 2008, published really a systematic review, an exhaustive systematic review of destructive procedures in the treatment of noncancer pain. And really, the quality of evidence is very low. The outcome metrics that were used in these studies were very poor. Very limited studies had controls. And so what we can glean from it is there really isn't a lot of data to support the use of these techniques in the management of patients that have nonmalignant pain. In contrast, the evidence for neuromodulation continues to grow, and we really are in an exciting time in that well-designed, high-quality studies are being performed. So, for example, in 2000, the first study of a randomized trial of spinal cord stimulation was put together where they compared patients who underwent spinal cord stimulation in physical therapy for complex regional pain syndrome and compared those outcomes to those patients that just underwent physical therapy alone. In 2002, we had a first randomized control study comparing intrathecal drug delivery for cancer pain against comprehensive medical management. You know, interestingly, I was helping a colleague study for the boards, and I found this slide that I made here in 2006 as a resident saying, spinal cord stimulation should be used as a last resort. And I think the evidence that we have moving forward has really shown that that's not really the case. So, you know, moving forward, in 2015, the SENZA trial was the first randomized control trial of spinal cord stimulation that really showed that high-quality outcomes can be achieved. And moving forward, we have studies in other realms as well. The evidence for neuromodulation is probably strongest today for chronic spinal pain. So, historically, I think people would have felt that spinal cord stimulation using tonic stimulation was valuable for leg pain. The SENZA trial showed that it was very effective for back pain as well, and really in a dramatic way. So, over the course of the first year, if patients had a baseline back pain score in the sevens, at the end of one year, their back pain score would be somewhere in the two-and-a-half range, a dramatic improvement. What's also notable is that the tonic group did well as well. So, I think people would have thought that back pain is difficult to cover with tonic stimulation historically. But even today, with the more advanced technology, tonic stimulation does provide significant improvements in back pain. And these results were carried forward to the two-year point as well. And now, we have an evidence-based treatment for complex regional pain syndrome and for forecausalgia. So, Dorsal Root in the ACCURIATE trial, published in 2017, we saw that dorsal root ganglion stimulation was superior to spinal cord stimulation in the management of these patients with these pain conditions. And the outcomes were really fairly impressive at the one-year outcome point. Now, with all innovations like this, we really need to get to the five-year point to see that this is a long-lasting and durable therapy. But it provides good solid evidence to say this is something that we can offer to our patients today. When I first started Baylor in 2010, my first referral was from Walter Reed. He was a master sergeant. He was a combat veteran and came down with chest wall pain and had undergone an injury to the chest wall. And I had just finished my fellowship, so I knew that destructive procedures for non-cancer pain were not the right thing to do. Nonetheless, I undertook a three-level thoracic ganglionectomy. Despite transient improvement, his pain came back and he continued to be miserable. But what's exciting today is due to scientists like Dr. Marshall DeVore and Dr. Pat Doherty at our institution, we know that the dorsal root ganglion is an important part of how pain is processed and how neuropathic pain exists. So this was a study in patients that were undergoing a vertebrectomy for cancer. And as you know, in a vertebrectomy, oftentimes you'll have to ligate the nerve roots. So it provided a nice opportunity to remove the dorsal root ganglion in humans. And what you can see is that the voltage-gated sodium channels from the dorsal root ganglion that were involved in patients that had neuropathic pain had a significant upregulation of these voltage-gated sodium channels as compared to the dorsal root ganglion that did not. So really, we have a solid footing to understand that the dorsal root ganglion is a primary source for where neuromodulation may have an effect. And so today, had Master Sergeant come to me, dorsal root ganglion would have been the first thing for me to offer him in a non-invasive and a non-destructive way. For cancer pain, neuromodulation serves an important role as well. In the randomized study comparing intrathecal drug delivery with comprehensive medical management, we know very clearly that intrathecal therapy does two things. One, it will clearly reduce side effects or opioid-induced toxicity. So patients will have less lethargy, less confusion. Interestingly, it also prolongs survival. So this is something that really you can go to your patient and provide them an evidence base to say that if you're suffering from cancer pain and have opioid-responsive symptoms, cancer pain can improve your quality of life and perhaps even improve your survival. For diagnoses, though, where there is level one evidence, I'd argue that neuromodulation still trumps ablation in the treatment of non-cancer pain. So if you look at occipital neuralgia, you have two treatments that are available for you, C-2 ganglionectomy and you have occipital nerve stimulation. Though ganglionectomy does provide some benefit, in the longer term, 40 percent of patients may have a poor outcome and 20 percent of patients may have a good outcome. On the other hand, if you look at a recent study from Emory with occipital stimulation used, 85 percent of patients will have a 50 percent improvement in paid improvement in one year, a one-year follower. So really, again, good supportive evidence to say a non-invasive or minimally invasive therapy can improve quality of life. And finally, even for pain conditions that historically we thought of as having no treatment or no effective treatment, we have well-designed clinical trials to provide some supportive evidence that neuromodulation may be effective. So by my face-off counterpart, Dr. Machado, we have a randomized controlled double-blinded study looking at deep brain stimulation of the anterior limb of the internal capsule and the ventral striatum and the treatment of post-stroke pain. So as opposed to all previous DBS for pain trials at the 3380 and 3387, both of which are largely heterogeneous groups with no blinding, this study can provide in a good way what outcomes patients can expect, though it was a small study. So though the study did not meet the primary endpoint, which is a reduction in the pain disability index score, 50 percent and 50 percent of the patients, what we did see is that the patients had significant improvements in the Montgomery Asperg depression scale and the Beck depression inventory and other scales that focused on the affective component of pain. So again, supportive evidence to say that this may be a therapy to further explore and perform larger trials on. So final thoughts. You know, I think today for non-cancer pain and even for many patients with cancer pain, neuromodulation should be our first thought. Certainly there exists a subset of patients that benefit from destructive therapies, but neuromodulation is a superior goal for us to seed. And I think we need to find and really look for designing trials to provide an evidence base to go to patients and improve quality of life. And if I were to redesign this trial today, I think ablation really is one that should be used as a last resort. You know, I'm not sure that anybody would, you know, if there is a neuromodulatory option, doing intracranial destructive procedures is probably not the right thing for patients. Thanks very much.

neuromodulation

pain procedures

chronic spinal pain

spinal cord stimulation

dorsal root ganglion stimulation