Cellular distribution of cannabinoid-related receptors TRPV1, PPAR-gamma, GPR55 and GPR3 in the equine cervical dorsal root ganglia
Cellular distribution of cannabinoid-related receptors TRPV1, PPAR-gamma, GPR55 and GPR3 in the equine cervical dorsal root ganglia
Background
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.
Objectives
To localise the cellular distribution of four putative cannabinoid-related receptors in the equine cervical dorsal root ganglia (DRG).
Study design
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.
Main limitations
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.
1 INTRODUCTION
In recent decades, a new source of pain relief has emerged, originating from an ancient pain-relieving medication (Cannabis sativa or hemp) which takes advantage of an endogenous ubiquitous pain control pathway, namely the endocannabinoid system (ECS).
The ECS is an extensive endogenous signalling system classically composed of cannabinoid receptors type 1 and 2 (CB1R and CB2R), the endocannabinoids N-arachidonylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG) and the enzymes responsible for endocannabinoid biosynthesis and degradation.1, 2
Endocannabinoids modulate the neural conduction of pain signals both by reducing the nociceptive neural signal of pain, and by reducing inflammation by activating cannabinoid receptors.2 The ECS may also be modulated by exposure to the phytocannabinoids contained in Cannabis sativa which contains more than 560 constituents and has a long history of medical use.3
However, Cannabis sativa contains high concentrations of two different cannabinoids, namely Δ9tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Studies carried out mainly on laboratory animals have indicated that CBD, unlike Δ9-THC, did not produce psychotropic effects and may exert beneficial effects on pain perception1, 4; in addition, CBD shows numerous health-related benefits, including anti-inflammatory, anti-spasmodic and anti-anxiety properties.5, 6
Recent scientific studies involving rodents and in vitro cultures of human cells have shown that the beneficial effects of phytocannabinoids are not only mediated by the CB1R and CB2R, but also by other cannabinoid-related receptors, such as the transient receptor potential (TRP) channels, the nuclear peroxisome proliferator-activated receptors (PPARs), G protein-coupled receptors (GPRs) and the serotonin receptors.4, 7
Our research team recently identified the cellular localisation of the canonical CB1R and CB2R, and the cannabinoid-related receptors TRPA1, PPAR-alpha and serotonin (5-HT) 1a receptor in the equine dorsal root ganglia (DRG).8
With the aim of providing a clearer understanding of the distribution of the receptors modulated by medical cannabis in equines, the current study localised the following four cannabinoid-related receptors, specifically modulated by CBD, in the equine DRG: transient receptors potential vanilloid 1 (TRPV1), nuclear peroxisome proliferator-activated receptor gamma (PPAR-γ), G-protein coupled receptors 55 (GPR55) and 3 (GPR3).
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Source: https://beva.onlinelibrary.wiley.com/doi/10.1111/evj.13305
