Cargando…

Non-peptidergic small diameter primary afferents expressing VGluT2 project to lamina I of mouse spinal dorsal horn

BACKGROUND: Unmyelinated primary afferent nociceptors are commonly classified into two main functional types: those expressing neuropeptides, and non-peptidergic fibers that bind the lectin IB4. However, many small diameter primary afferent neurons neither contain any known neuropeptides nor bind IB...

Descripción completa

Detalles Bibliográficos
Autores principales: Clarke, Jennifer N, Anderson, Rebecca L, Haberberger, Rainer V, Gibbins, Ian L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3264520/
https://www.ncbi.nlm.nih.gov/pubmed/22152428
http://dx.doi.org/10.1186/1744-8069-7-95
_version_ 1782221977439698944
author Clarke, Jennifer N
Anderson, Rebecca L
Haberberger, Rainer V
Gibbins, Ian L
author_facet Clarke, Jennifer N
Anderson, Rebecca L
Haberberger, Rainer V
Gibbins, Ian L
author_sort Clarke, Jennifer N
collection PubMed
description BACKGROUND: Unmyelinated primary afferent nociceptors are commonly classified into two main functional types: those expressing neuropeptides, and non-peptidergic fibers that bind the lectin IB4. However, many small diameter primary afferent neurons neither contain any known neuropeptides nor bind IB4. Most express high levels of vesicular glutamate transporter 2 (VGluT2) and are assumed to be glutamatergic nociceptors but their terminations within the spinal cord are unknown. We used in vitro anterograde axonal tracing with Neurobiotin to identify the central projections of these putative glutamatergic nociceptors. We also quantitatively characterised the spatial arrangement of these terminals with respect to those that expressed the neuropeptide, calcitonin gene-related peptide (CGRP). RESULTS: Neurobiotin-labeled VGluT2-immunoreactive (IR) terminals were restricted to lamina I, with a medial-to-lateral distribution similar to CGRP-IR terminals. Most VGluT2-IR terminals in lateral lamina I were not labeled by Neurobiotin implying that they arose mainly from central neurons. 38 ± 4% of Neurobiotin-labeled VGluT2-IR terminals contained CGRP-IR. Conversely, only 17 ± 4% of Neurobiotin-labeled CGRP-IR terminals expressed detectable VGluT2-IR. Neurobiotin-labeled VGluT2-IR or CGRP-IR terminals often aggregated into small clusters or microdomains partially surrounding intrinsic lamina I neurons. CONCLUSIONS: The central terminals of primary afferents which express high levels of VGluT2-IR but not CGRP-IR terminate mainly in lamina I. The spatial arrangement of VGluT2-IR and CGRP-IR terminals suggest that lamina I neurons receive convergent inputs from presumptive nociceptors that are primarily glutamatergic or peptidergic. This reveals a previously unrecognized level of organization in lamina I consistent with the presence of multiple nociceptive processing pathways.
format Online
Article
Text
id pubmed-3264520
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-32645202012-01-24 Non-peptidergic small diameter primary afferents expressing VGluT2 project to lamina I of mouse spinal dorsal horn Clarke, Jennifer N Anderson, Rebecca L Haberberger, Rainer V Gibbins, Ian L Mol Pain Research BACKGROUND: Unmyelinated primary afferent nociceptors are commonly classified into two main functional types: those expressing neuropeptides, and non-peptidergic fibers that bind the lectin IB4. However, many small diameter primary afferent neurons neither contain any known neuropeptides nor bind IB4. Most express high levels of vesicular glutamate transporter 2 (VGluT2) and are assumed to be glutamatergic nociceptors but their terminations within the spinal cord are unknown. We used in vitro anterograde axonal tracing with Neurobiotin to identify the central projections of these putative glutamatergic nociceptors. We also quantitatively characterised the spatial arrangement of these terminals with respect to those that expressed the neuropeptide, calcitonin gene-related peptide (CGRP). RESULTS: Neurobiotin-labeled VGluT2-immunoreactive (IR) terminals were restricted to lamina I, with a medial-to-lateral distribution similar to CGRP-IR terminals. Most VGluT2-IR terminals in lateral lamina I were not labeled by Neurobiotin implying that they arose mainly from central neurons. 38 ± 4% of Neurobiotin-labeled VGluT2-IR terminals contained CGRP-IR. Conversely, only 17 ± 4% of Neurobiotin-labeled CGRP-IR terminals expressed detectable VGluT2-IR. Neurobiotin-labeled VGluT2-IR or CGRP-IR terminals often aggregated into small clusters or microdomains partially surrounding intrinsic lamina I neurons. CONCLUSIONS: The central terminals of primary afferents which express high levels of VGluT2-IR but not CGRP-IR terminate mainly in lamina I. The spatial arrangement of VGluT2-IR and CGRP-IR terminals suggest that lamina I neurons receive convergent inputs from presumptive nociceptors that are primarily glutamatergic or peptidergic. This reveals a previously unrecognized level of organization in lamina I consistent with the presence of multiple nociceptive processing pathways. BioMed Central 2011-12-08 /pmc/articles/PMC3264520/ /pubmed/22152428 http://dx.doi.org/10.1186/1744-8069-7-95 Text en Copyright ©2011 Clarke et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Clarke, Jennifer N
Anderson, Rebecca L
Haberberger, Rainer V
Gibbins, Ian L
Non-peptidergic small diameter primary afferents expressing VGluT2 project to lamina I of mouse spinal dorsal horn
title Non-peptidergic small diameter primary afferents expressing VGluT2 project to lamina I of mouse spinal dorsal horn
title_full Non-peptidergic small diameter primary afferents expressing VGluT2 project to lamina I of mouse spinal dorsal horn
title_fullStr Non-peptidergic small diameter primary afferents expressing VGluT2 project to lamina I of mouse spinal dorsal horn
title_full_unstemmed Non-peptidergic small diameter primary afferents expressing VGluT2 project to lamina I of mouse spinal dorsal horn
title_short Non-peptidergic small diameter primary afferents expressing VGluT2 project to lamina I of mouse spinal dorsal horn
title_sort non-peptidergic small diameter primary afferents expressing vglut2 project to lamina i of mouse spinal dorsal horn
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3264520/
https://www.ncbi.nlm.nih.gov/pubmed/22152428
http://dx.doi.org/10.1186/1744-8069-7-95
work_keys_str_mv AT clarkejennifern nonpeptidergicsmalldiameterprimaryafferentsexpressingvglut2projecttolaminaiofmousespinaldorsalhorn
AT andersonrebeccal nonpeptidergicsmalldiameterprimaryafferentsexpressingvglut2projecttolaminaiofmousespinaldorsalhorn
AT haberbergerrainerv nonpeptidergicsmalldiameterprimaryafferentsexpressingvglut2projecttolaminaiofmousespinaldorsalhorn
AT gibbinsianl nonpeptidergicsmalldiameterprimaryafferentsexpressingvglut2projecttolaminaiofmousespinaldorsalhorn