Davis, O. C. et al. (2023) Calretinin-expressing islet cells are a source of pre- and post-synaptic inhibition of non-peptidergic nociceptor input to the mouse spinal cord. Scientific Reports, 13, 11561. (doi: 10.1038/s41598-023-38605-9) (PMID:37464016) (PMCID:PMC10354228)
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Abstract
Unmyelinated non-peptidergic nociceptors (NP afferents) arborise in lamina II of the spinal cord and receive GABAergic axoaxonic synapses, which mediate presynaptic inhibition. However, until now the source of this axoaxonic synaptic input was not known. Here we provide evidence that it originates from a population of inhibitory calretinin-expressing interneurons (iCRs), which correspond to lamina II islet cells. The NP afferents can be assigned to 3 functionally distinct classes (NP1–3). NP1 afferents have been implicated in pathological pain states, while NP2 and NP3 afferents also function as pruritoceptors. Our findings suggest that all 3 of these afferent types innervate iCRs and receive axoaxonic synapses from them, providing feedback inhibition of NP input. The iCRs also form axodendritic synapses, and their targets include cells that are themselves innervated by the NP afferents, thus allowing for feedforward inhibition. The iCRs are therefore ideally placed to control the input from non-peptidergic nociceptors and pruritoceptors to other dorsal horn neurons, and thus represent a potential therapeutic target for the treatment of chronic pain and itch.
| Item Type: | Articles |
|---|---|
| Additional Information: | Financial support from the Biotechnology and Biological Sciences Research Council (Grant numbers BB/J000620/1, BB/P007996/1 and BB/X000338/1), the National Health and Medical Research Council (NHMRC) of Australia (Grant numbers 631000 and 1043933), the Wellcome Trust (Grant numbers 102645/Z/13/Z and 219433/Z/19/Z), the Medical Research Council (Grant numbers MR/S002987/1 and MR/V033638/1), and the National Institute of Health (NIH; NS097344-08) is gratefully acknowledged. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Boyle, Dr Kieran and Hughes, Dr David I and Davis, Miss Olivia and Bell, Mr Andrew and Beresford-Polgar, Dr Erika and Todd, Professor Andrew and Kokai, Miss Eva and Dickie, Dr Allen and Browne, Mr Tyler |
| Authors: | Davis, O. C., Dickie, A. C., Mustapa, M. B., Boyle, K. A., Browne, T. J., Gradwell, M. A., Smith, K. M., Polgár, E., Bell, A. M., Kókai, É., Watanabe, M., Wildner, H., Zeilhofer, H. U., Ginty, D. D., Callister, R. J., Graham, B. A., Todd, A. J., and Hughes, D. I. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience |
| Journal Name: | Scientific Reports |
| Publisher: | Nature Research |
| ISSN: | 2045-2322 |
| ISSN (Online): | 2045-2322 |
| Copyright Holders: | Copyright © 2023 The Authors |
| First Published: | First published in Scientific Reports 13: 11561 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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