Pamela Blake MD
University of Texas Health Science Center at Houston
Houston, TX, SA
Please briefly introduce yourself, your co-authors, your respective fields of expertise, and the context/premise of your article.
I am a neurologist. I originally trained in Neuro-Ophthalmology in 1995, yet was increasingly drawn to Headache Medicine. I found the behavioral aspects of headache fascinating, and the options for treatment were much wider in Headache Medicine than in Neuro-Ophthalmology. After several years on the faculty at Georgetown, I relocated from Washington DC to Houston in 2006, and the hospital system which employed me there offered to me the opportunity to open a practice solely devoted to Headache, so at that point my practice became 100% Headache Medicine. I opened a private practice in 2019.
In 2004 I became exposed to nerve decompression surgery for chronic headache. Why the surgery should work was unclear at the time, as the prevailing opinion seemed to be that the pain of chronic headache emanated from central, or at least intracranial, processes. The surgery was very helpful for many of the patients, however, and became an important part of my practice by 2006. In 2009 I met Rami Burstein, and our collaboration began. Rami needs no introduction to the readers of this journal, as he is a highly regarded and widely published researcher from Harvard University. Rami observed several surgeries with my surgical colleague, Dr. Carlton Perry. Rami observed in the OR the compressive inflammatory tissue surrounding the occipital nerves. He rightly recognized the important role of this tissue in the mechanism of nerve compression, and he directed our research efforts accordingly. Our work over the years with regard to both basic science and clinical treatments has contributed to a growing understanding of the anatomy and pathophysiology of nerve compression and its role in chronic headache, as explained in the article, as well as how nerve compression headache may coexist with other, more clearly centrally-driven processes such as episodic migraine with aura.
Could you please give a short summary of your article and its findings/conclusions?
Our article ( Blake, P., Burstein, R. Emerging evidence of occipital nerve compression in unremitting head and neck pain. J Headache Pain 20, 76 (2019). https://doi.org/10.1186/s10194-019-1023-y) is a brief overview of current knowledge regarding the causes of pain in migraine, as well as a review of the pathophysiology of superficial nerve compression in chronic headache that is characterized by unremitting head and neck pain (UHNP), usually with associated occipital allodynia and cervical muscle spasm. The etiology of the pain of chronic headaches is not known. We do know is that many centrally directed treatments appear not to be effective, as they are often abandoned. Additionally, over the last 10-20 years, the role of treatments directed primarily at the periphery, such as botulinum toxin and CGRP monoclonal antibodies, has grown exponentially. These findings may be suggestive of a peripheral and even extracranial factor in chronic headaches, and superficial nerve compression is a candidate factor as the etiology of chronic headache.
The article goes on to review the mechanism of anatomic compression of the occipital nerves within the cervical musculature and the reasons for which inflammatory tissues may develop around the nerves, leading to further nerve compression and gradually increasing pain. This raises fascinating questions… for example, might this be a contributing factor to the so-called transformation from episodic migraine to chronic migraine? We touch briefly on the role of nerve decompression surgery, which continues to be an important part of my clinical practice
What are the implications of your article’s findings or the conclusions that could be drawn for practice, research, policy, or public health?
Ten years after the approval of Botox in the United States and the EU as an effective treatment of chronic migraine, chronic headache continues to be a leading cause of disability in both of these countries. Clearly, we have much more to learn and to offer regarding the etiology of chronic head and neck pain. I hope that pursuing research of peripheral factors including nerve compression, and, leading from that, the effect of nerve decompression in treating pain, will be a significant focus in Headache Medicine going forward.
Research in this area has been hampered by several factors: (1) the paradigm shift that is involved in considering extracranial and cervical factors as a possible main cause of chronic headache in some individuals; (2) challenges in conducting research on nerve decompression surgery, ranging from the lack of a clear funding source to the ethical challenges of conducting controlled clinical trial that would require sham (four- hour long, in the prone position) surgery, and (3) the lack of wider collaboration between Headache Medicine practitioners and plastic surgeons. This last factor has been particularly problematic. It has resulted in plastic surgeons identifying patients who they deem to be good surgical candidates and operating independently, and mistakes have been made in this regard. I think however that this moment should be an inflection point for the treatment of chronic migraine. I believe that the practice model that my current practice embodies, with the close collaboration of Headache Medicine, Plastic Surgery, Psychology (for both formal testing and treatment), and Physical Therapy is necessary, and should be the model for what Headache Medicine should look like in the future.
Where do you think the knowledge gaps still lie, and what challenges does this research face in the future?
We now know that pathophysiology in the occipital nerves that can lead to chronic headache with migraine features. Critical to this knowledge is the unravelling of the culprit. What causes the occipital nerves to be irritated? Is it anatomical malformation? Is it cellular, molecular or genetic deviation from normal? Is it inflammatory? Is it neuropathic? Is it secondary to muscular pathology? Does it originate in sick nerves or the tendons or bones they innervate? We know from cadaver studies that the anatomic placement of the occipital nerves within a cervical muscle is high – anywhere from 40-80% of cadavers – yet surely, and fortunately, 40-80% of people are not experiencing unremitting head and neck pain. It follows that the differentiating factor might be inflammation. What is the cause of the inflammation? The factor that I find most interesting and challenging and which flummoxes me on an almost daily basis is the role that stress and emotional factors play in pain. Certainly, we know from numerous excellent studies that stress is a very common trigger for episodic migraine. But what is its larger role in the development of chronic pain? Many of the patients I see with UHNP report the onset of their pain during a period of intense stress; the stress eventually abates, yet the pain persists. What role does that stress have in that situation? And what about those individuals with early life adversity? Often these are our most challenging patients. It has been shown that stress may affect inflammatory processes. Might chronic inflammatory effects be a cause for UHNP in these individuals? Of note, management of common comorbidities, particularly psychological conditions, is a critical aspect of successful reduction in headache during the process of nerve decompression.
Regarding challenges to research, many exist. Regarding surgery, the lack of a true placebo group is a major challenge. It is not possible, for ethical and safety reasons, to have a placebo group for a long surgery under general anesthesia in the prone position. The lack of a funding source is a second obstacle. A third is the need for the dissemination of more consistent surgical methods. Some individuals may have as many as eight branches of the lesser or greater occipital nerve, each of which is compressed within cervical musculature. The necessary surgical procedure requires systematically identifying and decompressing all the nerve branches, while leaving all the nerves intact. This results in a four-five-hour long procedure. There is currently wide variation among surgeons as to how the surgery is conducted, and Dr. Perry and I have seen the results of surgery performed by individuals who have not had proper training. Incorrectly performed surgery is not only harmful for the patient, it is harmful to the broader perception of the treatment. Finally, new metrics for research design are needed to separate out the effects of surgery on the pain caused by nerve compression from, for example, lingering migraine headaches triggered by stress or hormonal fluctuations.
Finally, are there any new developments in research surrounding chronic headache or pain etiology that you think are particularly exciting?
The current focus in Headache Medicine is on the role of CGRP and the effects of blocking its actions with antibodies that work largely in the periphery. This is indeed a fascinating area that dovetails with the concept of extracranial nerve compression. I am also excited by the growth of the field of psychoneuroimmunology, devoted to science of the interactions of mind and body, and what it can teach us about behavioral interventions such as mindfulness and meditation, and their effects on hormonal and inflammatory processes.