Cellular distribution of cannabinoid-related receptors TRPV1, PPAR-gamma, GPR55 and GPR3 in the equine cervical dorsal root ganglia.
Abstract: The activation of cannabinoid and cannabinoid-related receptors by endogenous, plant-derived or synthetic cannabinoids may exert beneficial effects on pain perception. Of the cannabinoids contained in Cannabis sativa, cannabidiol (CBD) does not produce psychotropic effects and seems to represent a molecule having great therapeutic potential. Cannabidiol acts on a great number of cannabinoid and cannabinoid-related G-protein-coupled receptors and ionotropic receptors which have, to date, been understudied in veterinary medicine particularly in equine medicine. Objective: To localise the cellular distribution of four putative cannabinoid-related receptors in the equine cervical dorsal root ganglia (DRG). Methods: A qualitative and quantitative immunohistochemical study. Methods: The cervical (C6-C8) DRG of six slaughtered horses were obtained from a local slaughterhouse. The tissues were fixed and processed for immunohistochemistry, and the resulting cryosections were used to investigate immunoreactivity for the following putative CBD receptors: Transient receptor potential vanilloid type 1 (TRPV1), nuclear peroxisome proliferator-activated receptor gamma (PPARγ), and G protein-coupled receptors 55 (GPR55) and 3 (GPR3). Results: Large percentages of neuronal cell bodies showed immunoreactivity for TRPV1 (80 ± 20%), PPARγ (100%), GPR55 (64 ± 15%) and GPR3 (63 ± 11%). The satellite glial cells (SGCs) were immunoreactive for TRPV1, PPARγ and GPR55. In addition, GPR55 immunoreactivity was expressed by DRG interneuronal macrophages. In addition, microglia cells were observed surrounding the neuron-SGC complex. Conclusions: The limited number of horses included in the study. Conclusions: Cannabinoid-related receptors were distributed in the sensory neurons (TRPV1, PPARγ, GPR55 and GPR3), SGCs (TRPV1, PPARγ and GPR55), macrophages (GPR55) and other interneuronal cells (PPARγ and GPR55) of the equine DRG. Given the key role of DRG cellular elements and cannabinoid receptors in the pathophysiology of pain, the present findings provided an anatomical basis for additional studies aimed at exploring the therapeutic uses of non-psychotropic cannabinoid agonists for the management of pain in horses.
© 2021 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
Publication Date: 2021-08-21 PubMed ID: 34418142PubMed Central: PMC9293124DOI: 10.1111/evj.13499Google Scholar: Lookup
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- Journal Article
Summary
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The research article investigates the specific locations of cannabinoid-related receptors in the horse’s cervical dorsal root ganglia (nerve clusters in the neck). It found that these receptors are present in a large percentage of nerve cells and other related cells, suggesting potential benefit in using non-psychotropic cannabinoids – like CBD – to manage horse pain.
Objective of the Research
- The aim of the study was to determine the distribution of four main cannabinoid-related receptors in the horse’s cervical dorsal root ganglia (DRG, nerve cell clusters in the neck). This research was focused on equine medicine and how cannabinoids, specifically Cannabidiol (CBD), could help in alleviating horse pain.
Methods Employed
- The researchers conducted both qualitative and quantitative immunohistochemical studies.
- The tissues required for these studies were derived from the cervical (C6-C8) DRG of six horses. These parts were later processed for immunohistochemistry.
- The primary goal here was to observe the immunoreactivity for cannabinoid-related receptors: TRPV1, PPARγ, GPR55, and GPR3, within these tissues. The researchers used cryosections from the fixed tissues for this purpose.
Research Findings
- The study found a significant percentage of neuronal cell bodies that were immunoreactive for all four cannabinoid-related receptors. Specifically, nearly 80% for TRPV1, 100% for PPARγ, 64% for GPR55, and 63% for GPR3.
- Cells known as satellite glial cells (SGCs) also showed immunoreactivity for TRPV1, PPARγ, and GPR55. DRG interneuronal macrophages expressed GPR55 immunoreactivity.
- Furthermore, microglial cells were observed surrounding the neuron-SGC complex, showing more complexity in the localization of these receptors.
Conclusions from the Study
- The cannabinoid-related receptors were found to be distributed in sensory neurons, SGCs, macrophages, and other interneuronal cells of the equine DRG.
- The presence of these receptors among these DRG cells indicates their potential role in the transmission and perception of pain. This offers a new potential avenue for pain management in horses, suggesting that non-psychotropic cannabinoid agonists could be used therapeutically.
- The study’s limitations include the small sample size of horses used in the investigation.
Cite This Article
APA
Galiazzo G, De Silva M, Giancola F, Rinnovati R, Peli A, Chiocchetti R.
(2021).
Cellular distribution of cannabinoid-related receptors TRPV1, PPAR-gamma, GPR55 and GPR3 in the equine cervical dorsal root ganglia.
Equine Vet J, 54(4), 788-798.
https://doi.org/10.1111/evj.13499 Publication
Researcher Affiliations
- Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
- Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
- Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
- Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
- Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
- Department of Veterinary Medical Sciences (UNI EN ISO 9001:2008), University of Bologna, Bologna, Italy.
Grant Funding
- Formula Swiss AG, Switzerland
Conflict of Interest Statement
No competing interests have been declared.
References
This article includes 62 references
Citations
This article has been cited 4 times.- Castillo-Arellano J, Canseco-Alba A, Cutler SJ, León F. The Polypharmacological Effects of Cannabidiol.. Molecules 2023 Apr 6;28(7).
- Zamith Cunha R, Zannoni A, Salamanca G, De Silva M, Rinnovati R, Gramenzi A, Forni M, Chiocchetti R. Expression of cannabinoid (CB1 and CB2) and cannabinoid-related receptors (TRPV1, GPR55, and PPARα) in the synovial membrane of the horse metacarpophalangeal joint.. Front Vet Sci 2023;10:1045030.
- Kuret T, Kreft ME, Romih R, Veranič P. Cannabidiol as a Promising Therapeutic Option in IC/BPS: In Vitro Evaluation of Its Protective Effects against Inflammation and Oxidative Stress.. Int J Mol Sci 2023 Mar 6;24(5).
- Kupczyk P, Rykala M, Serek P, Pawlak A, Slowikowski B, Holysz M, Chodaczek G, Madej JP, Ziolkowski P, Niedzwiedz A. The cannabinoid receptors system in horses: Tissue distribution and cellular identification in skin.. J Vet Intern Med 2022 Jul;36(4):1508-1524.
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