In fact, most animal studies of pain processing have been focused on nociceptive encoding and have contributed heavily to our mechanistic understanding of the brainstem's role in pain processing. Nociception is defined as the neural processes of encoding harmful stimuli, 72 and the brainstem plays a cardinal role in both nociception and acute pain processing. Brainstem nuclei involved in nociception and pain processing We will also provide promising examples of research demonstrating progress in human brainstem imaging to better understand the encoding of nociception and pain. Our review will highlight important challenges in brainstem neuroimaging (reviewed more in-depth elsewhere 108), particularly for nuclei purported to be linked with pain processing. Human functional magnetic resonance imaging (fMRI) studies have evaluated acute and chronic pain processing in the brainstem at both conventional (eg, 3 T) and ultrahigh-field (7 T and above) magnet strength, whereas structural MRI studies have assessed how gray matter volume and white matter integrity in the brainstem are associated with acute pain processing and are altered by chronic pain. It is composed of 3 distinct subregions-the medulla (most caudal), pons, and midbrain (most cranial). The brainstem is a critical area for nociception and pain processing, as well as relaying and coordinating signaling between the cerebrum, cerebellum, and spinal cord. However, we note that with recent advances in neuroimaging leading to improved spatial and temporal resolution, more studies are needed that take advantage of data collection and analysis methods focused on the challenges of brainstem neuroimaging. In fact, our review will highlight many pain neuroimaging studies that have reported some brainstem involvement in nociceptive processing and chronic pain pathology.
These challenges can require dedicated approaches to brainstem imaging, which should be adopted when study hypotheses are focused on brainstem processing of nociception or modulation of pain perception. The challenges for human brainstem imaging arise from the location of this elongated brain structure, proximity to cardiorespiratory noise sources, and the size of its constituent nuclei. Unfortunately, the brainstem is also a very challenging region to evaluate in humans with neuroimaging. Although preclinical models of pain have characterized the many roles that brainstem nuclei play in nociceptive processing, the degree to which these circuitries extend to humans is not as well known. The brainstem is known to be an important brain area for nociception and pain processing, and both relaying and coordinating signaling between the cerebrum, cerebellum, and spinal cord.
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This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, 149 13th St, Charlestown, MA 02129. Address: Department of Radiology, Center for Integrative Pain Neuroimaging (CiPNI), Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USAīDepartment of Radiology, Logan University, Chesterfield, MO, USAĬDepartment of Anatomy and Histology, University of Sydney, Sydney, New South Wales, Australia
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