The findings of a laboratory study suggest that cannabinoids have therapeutic potential for managing headshaking in horses.
The researchers tested 10 trigeminal ganglia from horses euthanized for reasons unrelated to the study, finding that cannabinoid receptors were present in good numbers in the nerve tissue.
This indicates they may be a useful response to therapeutic doses of the cannabis-derived chemicals, potentially easing the discomfort from the neuropathic pain that lies at the root of the hard-to-treat condition.
Rodrigo Zamith Cunha and his fellow researchers, writing in the International Journal of Molecular Sciences, said trigeminal-mediated headshaking is the most common neuropathic facial pain disorder in horses. Its reported prevalence in the United Kingdom is 4%.
“It can be a significant source of pain, compromised welfare, and wastage in horses, alongside safety concerns for riders and handlers,” they said.
The trigeminal nerve in horses originates behind the eye and has branches down to the mouth, nostrils and up to the ears.
Trigeminal-mediated headshaking shares some clinical similarities with human trigeminal neuralgia, the study team wrote. However, the underlying pathological mechanisms of the condition in horses appear to differ from human trigeminal neuralgia, with a functional rather than structural abnormality.
Researchers investigating human trigeminal neuralgia have explored the involvement of the neuromodulatory endocannabinoid system.
The system comprises endocannabinoid molecules involved in signaling processes, along with receptors such as the cannabinoid type 1 (CB1R) and type 2 (CB2R) receptors, and enzymes associated with ligand biosynthesis, activation, and degradation.
Cannabinoids derived from the cannabis plant, including cannabidiol (CBD), cannabigerol, cannabichromene, and cannabinol, as well as synthetic cannabinoids, act on these receptors and other cannabinoid-related receptors.
There is existing evidence suggesting that cannabinoids may effectively alleviate neuropathic pain by inhibiting neuronal transmission in pain pathways.
The authors noted that although there is limited university-led research on cannabis therapy in equines, in recent years several interesting studies have shown beneficial therapeutic effects of cannabinoid molecules in horses with extreme touch sensitivity, degenerative painful conditions such as osteoarthritis and laminitis, and also behavioral disturbances.
Consequently, cannabinoids could represent a promising therapeutic approach for the clinical management of trigeminal-mediated headshaking, provided the appropriate receptors could be identified in the equine trigeminal ganglion.
The researchers described their laboratory work to identify and characterise the expression of cannabinoid receptors and cannabinoid-related receptors in sections of the equine trigeminal ganglion.
They found that cannabinoid receptors (CB1 and CB2) and cannabinoid-related receptors (TRPV1, PPARɣ, and GPR55) are extensively expressed in the majority of equine trigeminal ganglion neurons. It WAs, they said, an encouraging discovery.
The study team said their work provides significant insights into the expression of CB1, CB2, GPR55, PPARγ, and TRPV1 in the trigeminal ganglia neurons and satellite glial cells of horses.
“The positive findings demonstrate the presence and potential functional significance of these receptors in the equine trigeminal ganglia, highlighting their potential role in the modulation of trigeminal nerve function and neuropathic pain pathways.”
Considering the known ability of cannabinoids to diminish pain, and the expression of these receptors in the trigeminal nerve, the findings hold promise for the therapeutic use of cannabinoids in managing headshaking in horses, they said.
“By targeting the endocannabinoid system, modulation of the trigeminal neural network and subsequent alleviation of trigeminal-mediated headshaking may be achievable.”
Investigation of receptor expression in cases of trigeminal mediated headshaking, and whether it differs from unaffected horses, is now being undertaken, they said.
“Such research endeavors could ultimately lead to the development of novel cannabinoid-based therapies for the clinical management of this debilitating condition, thereby enhancing the well-being, performance, and quality of life of these horses and improving safety for riders and handlers.”
The authors said further studies involving a larger number of subjects are required to confirm their results.
“It cannot be ruled out that some factors, such as the unknown underlying pathological conditions of the horses in the study or the medications they received, could potentially alter the CB1R, CB2R, TRPV1, GPR55, and PPARɣ expression in tissues.”
The study team comprised Zamith Cunha, Alberto Semprini, Giulia Salamanca, Francesca Gobbo, Maria Morini and Roberto Chiocchetti, all with the University of Bologna in Italy; Kirstie Pickles, with the University of Nottingham in England; and Veronica Roberts, with the University of Bristol.
Zamith Cunha, R.; Semprini, A.; Salamanca, G.; Gobbo, F.; Morini, M.; Pickles, K.J.; Roberts, V.; Chiocchetti, R. Expression of Cannabinoid Receptors in the Trigeminal Ganglion of the Horse. Int. J. Mol. Sci. 2023, 24, 15949. https://doi.org/10.3390/ijms242115949
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