Calcitonin receptor, calcitonin gene-related peptide and amylin distribution in C1/2 dorsal root ganglia
Abstract Background The upper cervical dorsal root ganglia (DRG) are important for the transmission of sensory information associated with the back of the head and neck, contributing to head pain. Calcitonin receptor (CTR)-based receptors, such as the amylin 1 (AMY1) receptor, and ligands, calcitoni...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | The Journal of Headache and Pain |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10194-024-01744-z |
| _version_ | 1797259122465308672 |
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| author | Tayla A. Rees Zoe Tasma Michael L. Garelja Simon J. O’Carroll Christopher S. Walker Debbie L. Hay |
| author_facet | Tayla A. Rees Zoe Tasma Michael L. Garelja Simon J. O’Carroll Christopher S. Walker Debbie L. Hay |
| author_sort | Tayla A. Rees |
| collection | DOAJ |
| description | Abstract Background The upper cervical dorsal root ganglia (DRG) are important for the transmission of sensory information associated with the back of the head and neck, contributing to head pain. Calcitonin receptor (CTR)-based receptors, such as the amylin 1 (AMY1) receptor, and ligands, calcitonin gene-related peptide (CGRP) and amylin, have been linked to migraine and pain. However, the contribution of this system to nociception involving the cervical DRG is unclear. Therefore, this study aimed to determine the relative distribution of the CTR, CGRP, and amylin in upper cervical DRG. Methods CTR, CGRP, and amylin immunofluorescence was examined relative to neural markers in C1/2 DRG from male and female mice, rats, and human cases. Immunofluorescence was supported by RNA-fluorescence in situ hybridization examining amylin mRNA distribution in rat DRG. Results Amylin immunofluorescence was observed in neuronal soma and fibres. Amylin mRNA (Iapp) was also detected. Amylin and CGRP co-expression was observed in 19% (mouse), 17% (rat), and 36% (human) of DRG neurons in distinct vesicle-like neuronal puncta from one another. CTR immunoreactivity was present in DRG neurons, and both peptides produced receptor signalling in primary DRG cell cultures. CTR-positive neurons frequently co-expressed amylin and/or CGRP (66% rat; 84% human), with some sex differences. Conclusions Amylin and CGRP could both be local peptide agonists for CTR-based receptors in upper cervical DRG, potentially acting through autocrine and/or paracrine signalling mechanisms to modulate neuron function. Amylin and its receptors could represent novel pain targets. |
| first_indexed | 2024-04-24T23:04:25Z |
| format | Article |
| id | doaj.art-08f9f4a08dc545469ba5b337cb58b3af |
| institution | Directory Open Access Journal |
| issn | 1129-2377 |
| language | English |
| last_indexed | 2024-04-24T23:04:25Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | The Journal of Headache and Pain |
| spelling | doaj.art-08f9f4a08dc545469ba5b337cb58b3af2024-03-17T12:33:16ZengBMCThe Journal of Headache and Pain1129-23772024-03-0125111510.1186/s10194-024-01744-zCalcitonin receptor, calcitonin gene-related peptide and amylin distribution in C1/2 dorsal root gangliaTayla A. Rees0Zoe Tasma1Michael L. Garelja2Simon J. O’Carroll3Christopher S. Walker4Debbie L. Hay5School of Biological Sciences, University of AucklandSchool of Biological Sciences, University of AucklandMaurice Wilkins Centre for Molecular Biodiscovery, University of AucklandDepartment of Anatomy and Medical Imaging, Centre for Brain Research, Faculty of Medical and Health Science, University of AucklandSchool of Biological Sciences, University of AucklandMaurice Wilkins Centre for Molecular Biodiscovery, University of AucklandAbstract Background The upper cervical dorsal root ganglia (DRG) are important for the transmission of sensory information associated with the back of the head and neck, contributing to head pain. Calcitonin receptor (CTR)-based receptors, such as the amylin 1 (AMY1) receptor, and ligands, calcitonin gene-related peptide (CGRP) and amylin, have been linked to migraine and pain. However, the contribution of this system to nociception involving the cervical DRG is unclear. Therefore, this study aimed to determine the relative distribution of the CTR, CGRP, and amylin in upper cervical DRG. Methods CTR, CGRP, and amylin immunofluorescence was examined relative to neural markers in C1/2 DRG from male and female mice, rats, and human cases. Immunofluorescence was supported by RNA-fluorescence in situ hybridization examining amylin mRNA distribution in rat DRG. Results Amylin immunofluorescence was observed in neuronal soma and fibres. Amylin mRNA (Iapp) was also detected. Amylin and CGRP co-expression was observed in 19% (mouse), 17% (rat), and 36% (human) of DRG neurons in distinct vesicle-like neuronal puncta from one another. CTR immunoreactivity was present in DRG neurons, and both peptides produced receptor signalling in primary DRG cell cultures. CTR-positive neurons frequently co-expressed amylin and/or CGRP (66% rat; 84% human), with some sex differences. Conclusions Amylin and CGRP could both be local peptide agonists for CTR-based receptors in upper cervical DRG, potentially acting through autocrine and/or paracrine signalling mechanisms to modulate neuron function. Amylin and its receptors could represent novel pain targets.https://doi.org/10.1186/s10194-024-01744-zDorsal root gangliaAmylinCalcitonin gene-related peptideAMY receptorsNeuropeptidesHeadache |
| spellingShingle | Tayla A. Rees Zoe Tasma Michael L. Garelja Simon J. O’Carroll Christopher S. Walker Debbie L. Hay Calcitonin receptor, calcitonin gene-related peptide and amylin distribution in C1/2 dorsal root ganglia The Journal of Headache and Pain Dorsal root ganglia Amylin Calcitonin gene-related peptide AMY receptors Neuropeptides Headache |
| title | Calcitonin receptor, calcitonin gene-related peptide and amylin distribution in C1/2 dorsal root ganglia |
| title_full | Calcitonin receptor, calcitonin gene-related peptide and amylin distribution in C1/2 dorsal root ganglia |
| title_fullStr | Calcitonin receptor, calcitonin gene-related peptide and amylin distribution in C1/2 dorsal root ganglia |
| title_full_unstemmed | Calcitonin receptor, calcitonin gene-related peptide and amylin distribution in C1/2 dorsal root ganglia |
| title_short | Calcitonin receptor, calcitonin gene-related peptide and amylin distribution in C1/2 dorsal root ganglia |
| title_sort | calcitonin receptor calcitonin gene related peptide and amylin distribution in c1 2 dorsal root ganglia |
| topic | Dorsal root ganglia Amylin Calcitonin gene-related peptide AMY receptors Neuropeptides Headache |
| url | https://doi.org/10.1186/s10194-024-01744-z |
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