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Equine veterinary journal2020; 53(3); 549-557; doi: 10.1111/evj.13305

Localisation of cannabinoid and cannabinoid-related receptors in the equine dorsal root ganglia.

Abstract: Growing evidence recognises cannabinoid receptors as potential therapeutic targets for pain. Consequently, there is increasing interest in developing cannabinoid receptor agonists for treating pain. As a general rule, to better understand the actions of a drug, it would be of extreme importance to know the cellular distribution of its specific receptors. The localisation of cannabinoid receptors in the dorsal root ganglia of the horse has not yet been investigated. Objective: To localise the cellular distribution of canonical and putative cannabinoid receptors in the equine cervical dorsal root ganglia. Methods: Qualitative and quantitative immunohistochemical study. Methods: Cervical (C6-C8) dorsal root ganglia were collected from six horses (1.5 years of age) at the slaughterhouse. The tissues were fixed and processed to obtain cryosections which were used to investigate the immunoreactivity of canonical cannabinoid receptors 1 (CB1R) and 2 (CB2R), and for three putative cannabinoid-related receptors: nuclear peroxisome proliferator-activated receptor alpha (PPARα), transient receptor potential ankyrin 1 (TRPA1) and serotonin 5-HT1a receptor (5-HT1aR). Results: The neurons showed immunoreactivity for CB1R (100%), CB2R (80% ± 13%), PPARα (100%), TRPA1 (74% ± 10%) and 5-HT1aR (84% ± 6%). The neuronal satellite glial cells showed immunoreactivity for CB2R, PPARα, TRPA1 and 5-HT1aR. Conclusions: The low number of horses included in the study. Conclusions: This study highlighted the expression of cannabinoid receptors in the sensory neurons and glial cells of the dorsal root ganglia. These findings could be of particular relevance for future functional studies assessing the effects of cannabinoids in horses to manage pain.
Publication Date: 2020-07-04 PubMed ID: 32524649DOI: 10.1111/evj.13305Google Scholar: Lookup
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  • Journal Article

Summary

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The research paper investigates the distribution of cannabinoid and cannabinoid-related receptors in the dorsal root ganglia (DRG) of horses, with the aim of understanding if they could be potential targets for pain management treatments.

Objective and Background

  • This study aims to investigate the cellular distribution of canonical and putative (proposed but not yet confirmed) cannabinoid receptors in the cervical dorsal root ganglia of horses.
  • With the mounting evidence that cannabinoid receptors can be potential targets for pain relief, understanding their distribution in an animal’s nervous system is essential for developing effective agonists.
  • The dorsal root ganglia, clusters of neurons in a vertebrate nervous system, play a key role in transmitting sensory information like pain from peripheral nerves to the spinal cord. Discovering a significant presence of cannabinoid receptors in these structures could lead to breakthroughs in pain management strategies.

Methodology

  • Dorsal root ganglia from the cervical region (C6-C8) of six horses, aged 1.5 years, were collected for this study.
  • The collected tissue samples underwent cryosectioning (a technique that involves freezing and slicing the tissue for microscopic examination).
  • These sections were then tested for the immunoreactivity of five types of receptors: two canonical cannabinoid receptors – CB1R and CB2R – and three proposed cannabinoid-related receptors: PPARα, TRPA1, and 5-HT1aR.

Results

  • The neurons tested displayed immunoreactivity for all five receptor types: 100% for CB1R and PPARα, 80% ± 13% for CB2R, 84% ± 6% for 5-HT1aR, and 74% ± 10% for TRPA1.
  • In addition, the neuronal satellite glial cells – non-neural cells that support and protect neurons – showed immunoreactivity to all but the CB1R receptors.

Conclusions

  • While the authors acknowledge the sample size of six horses was relatively small, they emphasize the study’s groundbreaking achievement: it highlights the significant presence of cannabinoid receptors in both sensory neurons and their supporting glial cells within the dorsal root ganglia of horses.
  • This discovery suggests potential for future research into the effects of cannabinoids in managing pain in horses and possibly other animals. It provides a foundation for further functional studies to validate cannabinoid receptors as targets for new pain relief strategies.

Cite This Article

APA
Chiocchetti R, Rinnovati R, Tagliavia C, Stanzani A, Galiazzo G, Giancola F, Silva M, Capodanno Y, Spadari A. (2020). Localisation of cannabinoid and cannabinoid-related receptors in the equine dorsal root ganglia. Equine Vet J, 53(3), 549-557. https://doi.org/10.1111/evj.13305

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 53
Issue: 3
Pages: 549-557

Researcher Affiliations

Chiocchetti, Roberto
  • Department of Veterinary Medical Sciences (UNI EN ISO), University of Bologna, Ozzano dell'Emilia, Italy.
Rinnovati, Riccardo
  • Department of Veterinary Medical Sciences (UNI EN ISO), University of Bologna, Ozzano dell'Emilia, Italy.
Tagliavia, Claudio
  • Department of Veterinary Medical Sciences (UNI EN ISO), University of Bologna, Ozzano dell'Emilia, Italy.
Stanzani, Agnese
  • Department of Veterinary Medical Sciences (UNI EN ISO), University of Bologna, Ozzano dell'Emilia, Italy.
Galiazzo, Giorgia
  • Department of Veterinary Medical Sciences (UNI EN ISO), University of Bologna, Ozzano dell'Emilia, Italy.
Giancola, Fiorella
  • Department of Veterinary Medical Sciences (UNI EN ISO), University of Bologna, Ozzano dell'Emilia, Italy.
Silva, Margherita De
  • Department of Veterinary Medical Sciences (UNI EN ISO), University of Bologna, Ozzano dell'Emilia, Italy.
Capodanno, Ylenia
  • Department of Veterinary Medical Sciences (UNI EN ISO), University of Bologna, Ozzano dell'Emilia, Italy.
Spadari, Alessandro
  • Department of Veterinary Medical Sciences (UNI EN ISO), University of Bologna, Ozzano dell'Emilia, Italy.

MeSH Terms

  • Animals
  • Cannabinoids
  • Ganglia, Spinal
  • Horses
  • Neurons
  • Pain / veterinary
  • Receptors, Cannabinoid

Grant Funding

  • Formula Swiss AG, Switzerland

References

This article includes 43 references
  1. Krames ES. The dorsal root ganglion in chronic pain and as a target for neuromodulation: a review.. Neuromodulation 2015;18:24-32.
  2. Esposito MF, Malayil R, Hanes M, Deer T. Unique characteristics of the dorsal root ganglion as a target for neuromodulation.. Pain Med 2019;20:S23-S30.
  3. Hanani M. Satellite glial cells in sensory ganglia: from form to function.. Brain Res Rev 2005;48:457-76.
  4. Ji RR, Berta T, Nedergaard M. Glia and pain: is chronic pain a gliopathy?. Pain 2013;154(Suppl 1):S10-28.
  5. Hogan QH. Labat lecture: the primary sensory neuron: where it is, what it does, and why it matters.. Reg Anesth Pain Med 2010;35:306-11.
  6. Calignano A, La Rana G, Giuffrida A, Piomelli D. Control of pain initiation by endogenous cannabinoids.. Nature 1998;394:277-81.
  7. Ligresti A, De Petrocellis L, Di Marzo V. From phytocannabinoids to cannabinoid receptors and endocannabinoids: pleiotropic physiological and pathological roles through complex pharmacology.. Physiol Rev 2016;96:1593-659.
  8. Pergolizzi JV Jr, Lequang JA, Taylor R Jr, Raffa RB, Colucci D. The role of cannabinoids in pain control: the good, the bad, and the ugly.. Minerva Anestesiol 2018;84:955-69.
  9. Yanes JA, McKinnell ZE, Reid MA, Busler JN, Michel JS, Pangelinan MM. Effects of cannabinoid administration for pain: A meta-analysis and meta-regression.. Exp Clin Psychopharmacol 2019;27:370-82.
  10. Kogan L, Schoenfeld-Tacher R, Hellyer P, Rishniw M. US Veterinarians' Knowledge, Experience, and Perception Regarding the Use of Cannabidiol for Canine Medical Conditions.. Front Vet Sci 2019;5:338.
  11. Ellis KL, Contino EK. Case Report: Treatment using cannabidiol in a horse with mechanical allodynia.. Equine vet Educ 2021;33:e79-e82.
  12. Williamson EM, Liu X, Izzo AA. Trends in use, pharmacology and clinical applications of emerging herbal nutraceuticals.. Br J Pharmacol 2020;177:1227-40.
  13. Mechoulam R, Peters M, Murillo-Rodriguez E, Hanus LO. Cannabidiol-recent advances.. Chem Biodivers 2007;4:1678-92.
  14. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin.. Br J Pharmacol 2008;153:199-215.
  15. Morales P, Hurst DP, Reggio PH. Molecular targets of the phytocannabinoids: a complex picture.. Prog Chem Org Nat Prod 2017;103:103-31.
  16. Ahluwalia J, Urban L, Capogna M, Bevan S, Nagy I. Cannabinoid 1 receptors are expressed in nociceptive primary sensory neurons.. Neuroscience 2000;100:685-8.
  17. Svízenská IH, Brázda V, Klusáková I, Dubový P. Bilateral changes of cannabinoid receptor type 2 protein and mRNA in the dorsal root ganglia of a rat neuropathic pain model.. J Histochem Cytochem 2013;61:529-47.
  18. Freundt-Revilla J, Kegler K, Baumgärtner W, Tipold A. Spatial distribution of cannabinoid receptor type 1 (CB1) in normal canine central and peripheral nervous system.. PLoS One 2017;12:e0181064.
  19. Chiocchetti R, Galiazzo G, Tagliavia C, Stanzani A, Giancola F, Menchetti M. Cellular distribution of canonical and putative cannabinoid receptors in canine cervical dorsal root ganglia.. Front Vet Sci 2019;6:313.
  20. Russo D, Bombardi C, Castellani G, Chiocchetti R. Characterization of spinal ganglion neurons in horse (Equus caballus). A morphometric, neurochemical and tracing study.. Neuroscience 2011;176:53-71.
  21. Giancola F, Rambaldi AM, Bianco F, Iusco S, Romagnoli N, Tagliavia C. Localization of the 5-hydroxytryptamine 4 receptor in equine enteric neurons and extrinsic sensory fibers.. Neurogastroenterol Motil 2017;29.
    doi: 10.1111/nmo.13045google scholar: lookup
  22. Wager-Miller J, Westenbroek R, Mackie K. Dimerization of G protein-coupled receptors: CB1 cannabinoid receptors as an example.. Chem Phys Lipids 2002;121:83-9.
  23. Anand U, Otto WR, Sanchez-Herrera D, Facer P, Yiangou Y, Korchev Y. Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of capsaicin responses in human sensory neurons.. Pain 2008a;138:667-80.
  24. Sánchez-Aparicio P, Florán B, Rodríguez Velázquez D, Ibancovichi JA, Varela Guerrero JA, Recillas S. Cannabinoids CB2 receptors, one new promising drug target for chronic and degenerative pain conditions in equine veterinary patients.. J Equine Vet Science 2020;85:102880.
  25. Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators.. Nature 1990;347:645-50.
  26. Lo Verme J, Fu J, Astarita G, La Rana G, Russo R, Calignano A. The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the antiinflammatory actions of palmitoylethanolamide.. Mol Pharmacol 2005;67:15-9.
  27. O'Sullivan SE. Cannabinoids go nuclear: evidence for activation of peroxisome proliferator-activated receptors.. Br J Pharmacol 2007;152:576-82.
  28. Burstein S. PPAR-gamma: a nuclear receptor with affinity for cannabinoids.. Life Sci 2005;77:1674-84.
  29. LoVerme J, Russo R, La Rana G, Fu J, Farthing J, Mattace-Raso G. Rapid broad-spectrum analgesia through activation of peroxisome proliferator-activated receptor-alpha.. J Pharmacol Exp Ther 2006;319:1051-61.
  30. Ho WSV, Kelly MEM. Cannabinoids in the cardiovascular system.. Adv Pharmacol 2017;80:329-66.
  31. Benyó Z, Ruisanchez É, Leszl-Ishiguro M, Sándor P, Pacher P. Endocannabinoids in cerebrovascular regulation.. Am J Physiol Heart Circ Physiol 2016;310:785-801.
  32. Brierley SM, Hughes PA, Page AJ, Kwan KY, Martin CM, O'Donnell TA. The ion channel TRPA1 is required for normal mechanosensation and is modulated by algesic stimuli.. Gastroenterology 2009;137:2084-2095.e3.
  33. McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M. TRPA1 mediates formalin-induced pain.. Proc Natl Acad Sci USA 2007;104:13525-30.
  34. Wang XL, Cui LW, Liu Z, Gao YM, Wang S, Li H. Effects of TRPA1 activation and inhibition on TRPA1 and CGRP expression in dorsal root ganglion neurons.. Neural Regen Res 2019;14:140-8.
  35. Akopian AN, Ruparel NB, Jeske NA, Hargreaves KM. Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization.. J. Physiol. London 2007;583:175-93.
  36. Anand U, Otto WR, Facer P, Zebda N, Selmer I, Gunthorpe MJ. TRPA1 receptor localisation in the human peripheral nervous system and functional studies in cultured human and rat sensory neurons.. Neurosci Lett 2008b;438:221-7.
  37. De Petrocellis L, Vellani V, Schiano-Moriello A, Marini P, Magherini PC, Orlando P. Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.. J Pharmacol Exp Ther 2008;325:1007-15.
  38. Richardson BP. Serotonin and nociception.. Ann NY Acad Sci 1990;600:511-9.
  39. Liu Z, Zhuang D, Lunderberg T, Yu L. Involvement of 5-hydroxytryptamine(1A) receptors in the descending anti- nociceptive pathway from periaqueductal gray to the spinal dorsal horn in intact rats, rats with nerve injury and rats with inflammation.. Neuroscience 2002;112:399-407.
  40. Haleem DJ. Serotonin-1A receptor dependent modulation of pain and reward for improving therapy of chronic pain.. Pharmacol Res 2018;134:212-9.
  41. Todorovic S, Anderson EG. Serotonin preferentially hyperpolarizes capsaicin-sensitive C type sensory neurons by activating 5-HT1A receptors.. Brain Res 1992;585:212-8.
  42. Yoder EJ, Tamir H, Ellisman MH. Serotonin receptors expressed by myelinating Schwann cells in rat sciatic nerve.. Brain Res 1997;753:299-308.
  43. Capano A, Weaver R, Burkman E. Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study.. Postgrad Med 2019;1-6.

Citations

This article has been cited 5 times.
  1. 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.
    doi: 10.3389/fvets.2023.1045030pubmed: 36937015google scholar: lookup
  2. Cunha RZ, Felisardo LL, Salamanca G, Marchioni GG, Neto OI, Chiocchetti R. The use of cannabidiol as a novel treatment for oral stereotypic behaviour (crib-biting) in a horse.. Vet Anim Sci 2023 Mar;19:100289.
    doi: 10.1016/j.vas.2023.100289pubmed: 36824298google scholar: lookup
  3. 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.
    doi: 10.1111/jvim.16467pubmed: 35801813google scholar: lookup
  4. Ford NC, Barpujari A, He SQ, Huang Q, Zhang C, Dong X, Guan Y, Raja SN. Role of primary sensory neurone cannabinoid type-1 receptors in pain and the analgesic effects of the peripherally acting agonist CB-13 in mice.. Br J Anaesth 2022 Jan;128(1):159-173.
    doi: 10.1016/j.bja.2021.10.020pubmed: 34844727google scholar: lookup
  5. Galiazzo G, De Silva M, Giancola F, Rinnovati R, Peli A, Chiocchetti R. Cellular distribution of cannabinoid-related receptors TRPV1, PPAR-gamma, GPR55 and GPR3 in the equine cervical dorsal root ganglia.. Equine Vet J 2021 Aug 21;54(4):788-98.
    doi: 10.1111/evj.13499pubmed: 34418142google scholar: lookup