Comprehensive phenotyping of cutaneous afferents reveals early-onset alterations in nociceptor response properties, release of CGRP, and hindpaw edema following spinal cord injury

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) increases nociceptor firing rates to reduced mechanical force applied to the skin.•SCI increases nociceptor firing to innocuous temperatures applied to the skin.•SCI increased the incidence of spontaneous activity (SA) and afterdischarge (AD).•SA occurs in low heat theshold...

Full description

Saved in:
Bibliographic Details
Published in:Neurobiology of pain Vol. 12; p. 100097
Main Authors: Eller, Olivia C., Stair, Rena N., Neal, Christopher, Rowe, Peter S.N., Nelson-Brantley, Jennifer, Young, Erin E., Baumbauer, Kyle M.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01-08-2022
Elsevier
Subjects:
Acute spinal cord injury
Below level
DRG
Inflammation
Original Research
Pain
Sensory neuron
DRG
Sensory neuron
Inflammation
Pain
Below level
Acute spinal cord injury
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•Spinal cord injury (SCI) increases nociceptor firing rates to reduced mechanical force applied to the skin.•SCI increases nociceptor firing to innocuous temperatures applied to the skin.•SCI increased the incidence of spontaneous activity (SA) and afterdischarge (AD).•SA occurs in low heat theshold nociceptors, while AD occurs in high heat threshold nocicpeotrs.•SCI results in hindpaw edema and increased CGRP release within the skin.•SCI-induced alterations in nociceptor response properties occur within the first 24 hr of 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 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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2452-073X
2452-073X
DOI:10.1016/j.ynpai.2022.100097