A Novel Role for the ‘Migraine Molecule’ Calcitonin Gene-Related Peptide in Neurogenic Bowel Pain and Dysfunction
Neurogenic bowel (NB) affects 60% of people with spinal cord injury (SCI) and is characterized by slow colonic transit, constipation, and chronic abdominal pain. NB rarely resolves and tends to worsen over time, making it a long-term challenge. The knowledge gap surrounding NB mechanisms after SCI m...
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Published in | The journal of pain Vol. 25; no. 4; p. 1 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
01.04.2024
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Online Access | Get full text |
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Summary: | Neurogenic bowel (NB) affects 60% of people with spinal cord injury (SCI) and is characterized by slow colonic transit, constipation, and chronic abdominal pain. NB rarely resolves and tends to worsen over time, making it a long-term challenge. The knowledge gap surrounding NB mechanisms after SCI means that interventions are primarily symptom-focused and largely ineffective. Identifying the mechanism(s) that initiate and maintain NB after SCI is critically important to the development of evidence-based, novel therapeutic options for NB after SCI. We employed tissue-specific, multi-omics approaches in a T8-10 mouse model of contusion SCI to characterize NB pathogenesis. Preliminary analyses indicate a rapid and persistent increase in expression of the inflammatory mediator, calcitonin gene-related peptide (CGRP), suggestive of neurogenic inflammation engaged by SCI. Intrarectal antagonism of CGRP activity significantly prevents NB-like phenotypes including colonic dysmotility, neoplastic lymphoid hyperplasias, and other structural defects of the colon. Interestingly, the effect of gut microbial dysbiosis including primary afferent hyperresponsiveness to fecal supernatants was also prevented by CGRP antagonism. This suggests that CGRP overexpression not only precedes microbiome dysbiosis but also that dysbiosis can be prevented by targeting CGRP at the time of injury. These data support the role for CGRP as a biological substrate for NB after SCI and a potential novel therapeutic target for the prevention of maladaptive colonic inflammation and gut dysbiosis in NB. |
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ISSN: | 1526-5900 1528-8447 |
DOI: | 10.1016/j.jpain.2024.01.009 |