Altered Brainstem Pain-Modulation Circuitry Connectivity During Spontaneous Pain Intensity Fluctuations
Received 5 March 2020
Accepted for publication 7 July 2020
Published 4 September 2020 Volume 2020:13 Pages 2223—2235
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Michael Schatman
Emily P Mills,1 Zeynab Alshelh,1 Danny Kosanovic,1 Flavia Di Pietro,1 E Russell Vickers,1 Paul M Macey,2 Luke A Henderson1
1Department of Anatomy and Histology, University of Sydney, Sydney, NSW 2006, Australia; 2School of Nursing and Brain Research Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
Correspondence: Luke A Henderson
Department of Anatomy and Histology, F13, University of Sydney, Sydney, NSW, Australia
Tel +612 9351 7063
Fax +612 9351 6556
Background: Chronic pain, particularly that following nerve injury, can occur in the absence of external stimuli. Although the ongoing pain is sometimes continuous, in many individuals the intensity of their pain fluctuates. Experimental animal studies have shown that the brainstem contains circuits that modulate nociceptive information at the primary afferent synapse and these circuits are involved in maintaining ongoing continuous neuropathic pain. However, it remains unknown if these circuits are involved in regulating fluctuations of ongoing neuropathic pain in humans.
Methods: We used functional magnetic resonance imaging to determine whether in 19 subjects with painful trigeminal neuropathy, brainstem pain-modulation circuitry function changes according to moment-to-moment fluctuations in spontaneous pain intensity as rated online over a 12-minute period.
Results: We found that when pain intensity was spontaneously high, connectivity strengths between regions of the brainstem endogenous pain-modulating circuitry—the midbrain periaqueductal gray, rostral ventromedial medulla (RVM), and the spinal trigeminal nucleus (SpV)—were high, and vice-versa (when pain was low, connectivity was low). Additionally, sliding-window connectivity analysis using 50-second windows revealed a significant positive relationship between ongoing pain intensity and RVM-SpV connectivity over the duration of the 12-minute scan.
Conclusion: These data reveal that moment-to-moment changes in brainstem pain-modulation circuitry functioning likely contribute to fluctuations in spontaneous pain intensity in individuals with chronic neuropathic pain.
Keywords: midbrain periaqueductal gray matter, rostral ventromedial medulla, spinal trigeminal nucleus, dynamic connectivity, functional connectivity, spontaneous pain
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]