Research study: Localisation of cannabinoid and cannabinoid-related receptors in the equine dorsal root ganglia (horses)

Research study: Localisation of cannabinoid and cannabinoid-related receptors in the equine dorsal root ganglia (horses)

We work with the very best researchers and universities around the World to gain valuable knowledge about, how CBD products work in humans and animals and to get detailed information about, how the cannabinoids react with the CB1 and CB2 receptors.

We work with University of Bologna and Professor Roberto Chiocchetti DVM, PhD. and his team from Department of Veterinary Medical Science and are funding a number of research studies on CBD and animals.

Disclaimer: we supported the University of Bologna with financial funds for research. The authors declare they have no conflict of interest.

Research study: Localisation of cannabinoid and cannabinoid-related receptors in the equine dorsal root ganglia (horses)

Summary

A growing body of evidence indicates that activation of cannabinoid receptors, i.e. the receptors activated by endogenous or plant-derived cannabinoids may influence and reduce, at different levels (central and peripheral), the somatic and visceral pain. Cannabidiol (CBD), which has no psychotropic effects, seems to be the most studied and promising molecule, thanks to its remarkable pain-relieving properties.

The main goal of this study was to explore the distribution of CBD receptors in the sensory neurons of the peripheral nervous system of the horse.

The sensory neurons are grouped in the small ganglia (spinal ganglia) distributed along the spinal cord of human and animals. The sensory neurons are also present in the head, for instance in the trigeminal ganglia, and their function is to support the face and skull sensitivity. Sensory ganglia contain the cell bodies of primary sensory neurons, which are surrounded by a layer of satellite glial cells. These neurons send their long processes to the bones, muscle, joints, skin, internal and external organs, and transduce the painful and non-painful (touch, cold, warm, for example) stimuli in neuro-electric signals, which reach the central nervous system. Chronic pain is associated with hyper excitability of the sensory neurons and their down-modulation could thereby decrease pain.

Since the research on the use of therapeutic cannabis on horses is at present very scarce, we thought that this was a very good reason to learn more from a scientific point of view.

We successfully demonstrated that CBD receptors have a wide distribution in the sensory neurons and glial cells of the equine spinal ganglia. The finding of our study, supported by Formula Swiss, represents an important anatomical basis upon which it will be possible to continue with other preclinical and clinical studies aimed at investigating and possibly supporting the specific therapeutic uses of non-psychotropic CBD and other cannabinoid agonists against noxious stimulation in horses.

Background

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.
Objectives: To localise the cellular distribution of canonical and putative cannabinoid receptors in the equine cervical dorsal root ganglia.

Even though limited empirical research has been carried out concerning the use of medical marijuana for pain treatment in domestic animals and horses, the use of cannabis products in animals is expanding. Of the cannabis products, cannabidiol (CBD), a non-psychoactive compound found in cannabis sativa, seems to be one of the most promising therapeutic substances. Due to its numerous health-related benefits, CBD has found multiple clinical applications in the medical field, including analgesic, anti-in- flammatory, anti-spasmodic and anti-anxiety uses. For many years, it was assumed that the beneficial effects of the cannabinoids were mediated exclusively by cannabinoid receptors 1 (CB1R) and 2 (CB2R). However, it is currently known that phytocannabinoids may act on multiple targets outside the endocannabinoid system, such as other G-protein-coupled receptors (GPRs), the transient receptors potential (TRPs) channel, nuclear peroxisome proliferator-activated receptors (PPARs), and serotonin receptors. In particular, CBD, which shows indirect interaction with CB1R and CB2R, seems to be involved in the modulation of receptors, such as the serotoninergic 5-HT1a receptor (5-HT1aR), and the transient receptors potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1), the latter two being ex- citatory ion channels expressed by the sensory neurons mediating somatic and visceral pain.

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.

As a general rule, to better understand the effects exerted by a drug, it is important to know the cellular distribution of its specific receptors. Currently, only a small number of studies have been pub- lished regarding the expression of cannabinoid receptors in the dorsal root ganglia of animals and no analogous studies have yet been carried out on horses.

Thus, the current study was designed to immunohistochemically localise, two canonical cannabinoid receptors (CB1R and CB2R) and three cannabinoid-related receptors (PPARα, TRPA1 and 5-HT1aR) in the equine dorsal root ganglia.

Conclusions:

Cannabinoid and cannabinoid-related receptors had a wide distribution in the sensory neurons and SGCs of the equine dorsal root ganglia. These findings represented an important anatomical basis upon which it would be possible to continue with other preclinical and clinical studies aimed at investigating and possibly supporting the specific therapeutic uses of non-psychotropic cannabinoid agonists against noxius stimulation in horses.

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