Comprehensive phenotyping of cutaneous afferents reveals early-onset alterations in nociceptor response properties, release of CGRP, and hindpaw edema following spinal cord injury
Spinal cord injury (SCI) is a complex syndrome that has profound effects on patient well-being, including the development of medically-resistant chronic pain. The mechanisms underlying SCI pain have been the subject of thorough investigation but remain poorly understood. While the majority of the re...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | Neurobiology of Pain |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452073X22000149 |
| _version_ | 1828168055226630144 |
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| author | Olivia C. Eller Rena N. Stair Christopher Neal Peter S.N. Rowe Jennifer Nelson-Brantley Erin E. Young Kyle M. Baumbauer |
| author_facet | Olivia C. Eller Rena N. Stair Christopher Neal Peter S.N. Rowe Jennifer Nelson-Brantley Erin E. Young Kyle M. Baumbauer |
| author_sort | Olivia C. Eller |
| collection | DOAJ |
| description | Spinal cord injury (SCI) is a complex syndrome that has profound effects on patient well-being, including the development of medically-resistant chronic pain. The mechanisms underlying SCI pain have been the subject of thorough investigation but remain poorly understood. While the majority of the research has focused on changes occurring within and surrounding the site of injury in the spinal cord, there is now a consensus that alterations within the peripheral nervous system, namely sensitization of nociceptors, contribute to the development and maintenance of chronic SCI pain. Using an ex vivo skin/nerve/DRG/spinal cord preparation to characterize afferent response properties following SCI, we found that SCI increased mechanical and thermal responding, as well as the incidence of spontaneous activity (SA) and afterdischarge (AD), in below-level C-fiber nociceptors 24 hr following injury relative to naïve controls. Interestingly, the distribution of nociceptors that exhibit SA and AD are not identical, and the development of SA was observed more frequently in nociceptors with low heat thresholds, while AD was found more frequently in nociceptors with high heat thresholds. We also found that SCI resulted in hindpaw edema and elevated cutaneous calcitonin gene-related peptide (CGRP) concentration that were not observed in naïve mice. These results suggest that SCI causes a rapidly developing nociceptor sensitization and peripheral inflammation that may contribute to the early emergence and persistence of chronic SCI pain. |
| first_indexed | 2024-04-12T02:27:48Z |
| format | Article |
| id | doaj.art-69f9dc9ba4e84c22afe896b67e840c2a |
| institution | Directory Open Access Journal |
| issn | 2452-073X |
| language | English |
| last_indexed | 2024-04-12T02:27:48Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Pain |
| spelling | doaj.art-69f9dc9ba4e84c22afe896b67e840c2a2022-12-22T03:51:55ZengElsevierNeurobiology of Pain2452-073X2022-08-0112100097Comprehensive phenotyping of cutaneous afferents reveals early-onset alterations in nociceptor response properties, release of CGRP, and hindpaw edema following spinal cord injuryOlivia C. Eller0Rena N. Stair1Christopher Neal2Peter S.N. Rowe3Jennifer Nelson-Brantley4Erin E. Young5Kyle M. Baumbauer6Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, United StatesDepartment of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, United StatesKansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS, United StatesDepartment of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, United States; The Kidney Institute & Division of Nephrology, University of Kansas Medical Center, Kansas City, KS, United StatesDepartment of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, United StatesDepartment of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, United States; Department of Anesthesiology, University of Kansas Medical Center, Kansas City, KS, United States; Center for Advancement in Managing Pain, School of Nursing, University of Connecticut, Storrs, CT, United States; Department of Genetics and Genome Sciences, UConn Health, Farmington, CT, United States; Department of Neuroscience, UConn Health, Farmington, CT, United StatesDepartment of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, United States; Department of Anesthesiology, University of Kansas Medical Center, Kansas City, KS, United States; Center for Advancement in Managing Pain, School of Nursing, University of Connecticut, Storrs, CT, United States; Department of Neuroscience, UConn Health, Farmington, CT, United States; Corresponding author at: Department of Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow Blvd, MS 3051, Kansas City, KS 66160, United States.Spinal cord injury (SCI) is a complex syndrome that has profound effects on patient well-being, including the development of medically-resistant chronic pain. The mechanisms underlying SCI pain have been the subject of thorough investigation but remain poorly understood. While the majority of the research has focused on changes occurring within and surrounding the site of injury in the spinal cord, there is now a consensus that alterations within the peripheral nervous system, namely sensitization of nociceptors, contribute to the development and maintenance of chronic SCI pain. Using an ex vivo skin/nerve/DRG/spinal cord preparation to characterize afferent response properties following SCI, we found that SCI increased mechanical and thermal responding, as well as the incidence of spontaneous activity (SA) and afterdischarge (AD), in below-level C-fiber nociceptors 24 hr following injury relative to naïve controls. Interestingly, the distribution of nociceptors that exhibit SA and AD are not identical, and the development of SA was observed more frequently in nociceptors with low heat thresholds, while AD was found more frequently in nociceptors with high heat thresholds. We also found that SCI resulted in hindpaw edema and elevated cutaneous calcitonin gene-related peptide (CGRP) concentration that were not observed in naïve mice. These results suggest that SCI causes a rapidly developing nociceptor sensitization and peripheral inflammation that may contribute to the early emergence and persistence of chronic SCI pain.http://www.sciencedirect.com/science/article/pii/S2452073X22000149Acute spinal cord injuryBelow levelPainDRGSensory neuronInflammation |
| spellingShingle | Olivia C. Eller Rena N. Stair Christopher Neal Peter S.N. Rowe Jennifer Nelson-Brantley Erin E. Young Kyle M. Baumbauer Comprehensive phenotyping of cutaneous afferents reveals early-onset alterations in nociceptor response properties, release of CGRP, and hindpaw edema following spinal cord injury Neurobiology of Pain Acute spinal cord injury Below level Pain DRG Sensory neuron Inflammation |
| title | Comprehensive phenotyping of cutaneous afferents reveals early-onset alterations in nociceptor response properties, release of CGRP, and hindpaw edema following spinal cord injury |
| title_full | Comprehensive phenotyping of cutaneous afferents reveals early-onset alterations in nociceptor response properties, release of CGRP, and hindpaw edema following spinal cord injury |
| title_fullStr | Comprehensive phenotyping of cutaneous afferents reveals early-onset alterations in nociceptor response properties, release of CGRP, and hindpaw edema following spinal cord injury |
| title_full_unstemmed | Comprehensive phenotyping of cutaneous afferents reveals early-onset alterations in nociceptor response properties, release of CGRP, and hindpaw edema following spinal cord injury |
| title_short | Comprehensive phenotyping of cutaneous afferents reveals early-onset alterations in nociceptor response properties, release of CGRP, and hindpaw edema following spinal cord injury |
| title_sort | comprehensive phenotyping of cutaneous afferents reveals early onset alterations in nociceptor response properties release of cgrp and hindpaw edema following spinal cord injury |
| topic | Acute spinal cord injury Below level Pain DRG Sensory neuron Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S2452073X22000149 |
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