Logan University’s Department of Radiology held the 16th Annual Joseph W. Howe Oration in Diagnostic Imaging in early June. This Oration is hosted and moderated by Norman Kettner, DC, DACBR, FICC, Dean of Research and Emeritus Professor of Logan’s Department of Radiology and is designed to honor the extensive contributions and achievements of radiologist, clinician and mentor Joseph Howe, DC, DACBR to the education, research and practice of chiropractic radiology.
Every year, eminent speakers have been selected to deliver the Oration from the fields of radiology, clinical practice, education and research, reflecting the extraordinarily wide scope of intellectual interest and contributions in the career of Dr. Joseph Howe. This year’s Oration address was delivered by Marco Loggia, PhD, Associate Professor of Radiology for Harvard Medical School, Co-Director for the Center for Integrative Pain NeuroImaging (CIPNI) and faculty member for Massachusetts General Hospital and the Athinoula A. Martinos Center for Biomedical Imaging. Most of Dr. Loggia’s work is focused on the brain imaging of neuroimmune responses, which is associated with chronic pain. Notably, in 2014, Dr. Loggia published a seminal landmark paper in the Journal Brain that linked the role of the glial cells of the brain, immune cells of the brain and chronic pain, which opened the doorway to many new directions of research. His lecture during the Howe Oration addressed imaging pain-related inflammation in humans using integrated PET/MRI.
Dr. Loggia began by stating that neuroinflammation in the central nervous system involves various cellular players, including microglia, astrocytes, and sometimes infiltrating peripheral immune cells. Neuroinflammation can be triggered by factors such as viral or bacterial infections, neurodegeneration, aging, autoimmunity, toxic metabolites, neural activity, injury and pollution. Even neural activity itself can lead to inflammation due to cellular sensitivity to the microenvironment.
Dr. Loggia stated, “The nature of neuroinflammation can be both beneficial and detrimental.” In an acute context, it can help identify and limit potential harm while facilitating repair. However, chronic or exaggerated neuroinflammation can become maladaptive or pathogenic.
Glia cells play a role in human pain, particularly in response to injury. When glial cells react and initiate a cellular response, they release inflammatory mediators that sensitize pain, creating a pain loop. Blocking this response pharmacologically can reduce or inhibit pain.
“Establishing a clear link between neuroinflammation and human pain remains challenging due to limitations in visualizing brain inflammation,” said Dr. Loggia. Using the Translocator protein (TSPO) to image neuroinflammation has provided insights. TSPO is elevated in neurodegenerative disorders like Multiple Sclerosis, Huntington’s Disease and Neuromuscular Disorders, correlating with pathology and inflammation.
Dr. Loggia explains that notably, TSPO signals have been observed in chronic pain, and this signal correlates with comorbid depression. The amount of neuroinflammation in the cortex appears to be linked to nociplastic pain, characterized by changes in the central nervous system that result in more intense or widespread pain than expected based on the presence of a lesion.
“A theme emerging from all of the studies we have been doing is that the clinical and functional significance of this neuroinflammatory signal that we see elevated in patients with chronic pain, really depends on the brain region that we are looking at. In some regions, it’s linked to clinical pain presentation; in other regions, it’s linked to maybe fatigue, and in other regions it’s involved with negative affect. About 40% of patients with chronic pain conditions have anxiety or depression,” said Dr. Loggia.
Studies also revealed that the clinical and functional significance of neuroinflammatory signals varies based on the brain region, with some regions associated with clinical pain, fatigue or negative affect.
Research extended to other chronic pain disorders like Fibromyalgia, Gulf War Illness and migraines, where widespread TSPO signal elevation was observed. Surgical treatment reduced TSPO signals, suggesting its potential as a marker for tracking treatment response. High neuroinflammatory signals before surgery predict poorer treatment outcomes, emphasizing the central role of the brain and spinal cord in maintaining pain. TSPO’s applicability isn’t limited to the brain. It has been studied in the spinal cord, sciatica and joint inflammation, showing promise as a marker for glial activation.
The relationship between TSPO signals, neuroinflammation and neuroplasticity is under investigation, particularly in conditions like Carpal Tunnel Syndrome.
Dr. Loggia shares that environmental factors, including the stress and isolation brought about by the COVID-19 pandemic, have been linked to elevated neuroinflammation. This was accompanied by an increase in blood markers of inflammation and changes in brain aging.
Dr. Loggia concludes that TSPO shows potential as an imaging marker for both central and peripheral inflammation, responding to treatments and being influenced by environmental factors. Targeting inflammation/neuroinflammation may offer therapeutic options for chronic pain and related comorbidities. However, further research and efforts to make neuroinflammation imaging more accessible are necessary to advance our understanding of these complex processes.
About Marco Loggia, PhD
In 2008, Dr. Loggia was awarded a PhD in Neurological Sciences by McGill University in Montreal, Canada. During his graduate studies, he worked at the Alan Edwards Centre for Research on Pain, formerly McGill Centre for Research on Pain, and was mentored by the director, Professor M. Catherine Bushnell, a pioneer in the field of human pain imaging. Between 2008 and 2013, Dr. Loggia was a research fellow at Harvard Medical School and worked in the laboratory of Drs. Robert R. Edwards and Ajay D. Wasan. He has been recognized by the International Association of the Study of Pain (IASP) receiving the 2013 Early Career Award and in 2016 he received the ISAP Ulf Lindblom Young Investigator Award for Clinical Science.
Dr. Loggia has published over 86 publications and has received countless federal and foundational grants. He is enthusiastic to mentor the next generation and is part of the MIT Science and Technology group to mentor aspiring students.