The making of..

..our just published paper of tACS for the treatment of chronic pain (abstract here). Today, I would like to share with you how we got started with this exciting new research direction and how things came together for that study.

Origin of the Idea
Before we initiated this work, we had not studied chronic pain. A graduate student approached me with the desire to develop a new treatment for chronic pain and I sensed a great opportunity to support her idea and initiative. The principal investigator for this study was Dr. Karen McCulloch, faculty at the UNC School of Medicine. The first step was a review of the literature and what we found was that there are only very few (perhaps less than 10) scientific publications on how brain activity is altered in chronic pain. To my surprise, the vast majority of research is focused on acute pain, which we hypothesized to be very different from chronic pain, which is persisting pain even if the original cause of the pain is long gone.

Our Idea
As an outsider, we had the freedom to not be bogged down by existing paradigms and research cultures. Our idea was straightforward. We hypothesized that there is a change in the alpha oscillations, which is a fundamental brain rhythm impaired in many disorders of the central nervous system, and that transcranial alternating current stimulation (tACS) can restore alpha oscillations and thus reduce pain symptoms in patients with chronic pain. More specifically, we speculated that alpha oscillations are reduced (corresponding to elevated neuronal firing) in the areas of the brain encoding touch.

Our Study
With this hypothesis in mind, we planned and executed a double-blind, placebo controlled study, which is described in our new paper (NCT03243084). To my surprise, we found convincing evidence for the hypotheses. Typically, in any scientific study, about 80% of the results make sense (on a good day!) and 20% leave you more confused (next study!). In this case, it was unusual how well everything lined up.

Getting it Published
The process was very smooth (highly unusual!). As you would expect for a new idea, we first were met with an editorial rejection from one of the leading journals in the pain field. We tried another, equally established journal, made it passed the editorial pre-screen and both reviewers were enthusiastic and incredibly helpful. Paper accepted.

Parting Thought
This was a highly synergistic collaboration between two outstanding trainees in my group Dr. Sangtae Ahn (postdoc) and Julianna Prim (graduate student, co-mentored with Dr. McCulloch). They have complementary expertise which was needed for such a new and exciting study. When I asked them why this all worked out so well, the answer I got was that I asked them to sit at neighboring desks, which facilitated their collaboration. Small details do matter!

Take care,

Flavio
PS While our first study looks really exciting, no single study can provide any final answer and much more work will be needed before this becomes a clinical treatment. This study was mostly a neuroscience study to understand if there are indeed brain rhythms which are impaired in chronic pain and if tACS can engage these rhythms. If you are interested in this kind of work, please consider a donation to enable this line of research. Also, you need to know that the study was performed with a device from my start-up company Pulvinar Neuro LLC. The company played no role in this study.