Preliminary investigation of potential links between pigmentation variants and opioid analgesic effectiveness in horses during cerebrospinal fluid centesis.
Abstract: The pleiotropic effects of the melanocortin system show promise in overcoming limitations associated with large variations in opioid analgesic effectiveness observed in equine practice. Of particular interest is variation in the melanocortin-1-receptor (MC1R) gene, which dictates pigment type expression through its epistatic interaction with the agouti signalling protein (ASIP) gene. MC1R has previously been implicated in opioid efficacy in other species; however, this relationship is yet to be explored in horses. In this study, analgesic effectiveness was scored (1-3) based on noted response to dura penetration during the performance of cerebrospinal fluid centisis after sedation and tested for association with known genetic regions responsible for pigmentation variation in horses. Results: The chestnut phenotype was statistically significant (P < 0.05) in lowering analgesic effectiveness when compared to the bay base coat colour. The 11bp indel in ASIP known to cause the black base coat colour was not significant (P>0.05); however, six single nucleotide polymorphisms (SNPs) within the genomic region encoding the ASIP gene and one within MC1R were identified as being nominally significant (P<0.05) in association with opioid analgesic effectiveness. This included the location of the known e MC1R variant resulting in the chestnut coat colour. Conclusions: The current study provides promising evidence for important links between pigmentation genes and opioid effectiveness in horses. The application of an easily identifiable phenotype indicating variable sensitivity presents a promising opportunity for accessible precision medicine in the use of analgesics and warrants further investigation.
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Publication Date: 2024-07-12 PubMed ID: 38997753PubMed Central: PMC11245827DOI: 10.1186/s12917-024-04139-zGoogle Scholar: Lookup
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Summary
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The research article investigates the potential relationship between genetic variations responsible for pigmentation in horses and the effectiveness of opioid analgesics. A particular focus was given to the melanocortin-1-receptor (MC1R) gene and the agouti signalling protein (ASIP) gene. The study found promising links that need further exploration.
Study Objectives and Methods
- The study aims to explore whether there’s any relationship between genetic variations in pigmentation and the effectiveness of opioid analgesics in horses.
- The melanocortin-1-receptor (MC1R) gene and the agouti signalling protein (ASIP) gene are particularly scrutinized as these are responsible for pigment type expression.
- The study quantifies analgesic effectiveness by providing a score (1-3) based on the observed response of horses to dura penetration during cerebrospinal fluid centisis post-sedation.
- The impact of known genetic regions responsible for pigmentation variation on the measured analgesic effectiveness is then statistically analyzed.
Results and Findings
- The findings suggest that the chestnut phenotype significantly impacts analgesic effectiveness, resulting in lower effectiveness compared to the bay base coat colour.
- The 11bp indel in ASIP known to cause the black base coat colour wasn’t found to be influential.
- However, six single nucleotide polymorphisms (SNPs) within the genomic region coding the ASIP gene and one SNP within MC1R were discovered to be significantly associated with opioid analgesic effectiveness.
- In particular, the location of a known e MC1R variant that results in the chestnut coat colour is included among these significant SNPs.
Conclusions and Implications
- The research gives promising evidence of a connection between pigmentation genes and the effectiveness of opioids in horses.
- This finding suggests that easily identifiable phenotypes could be used as indicators of variable sensitivity to analgesics.
- This discovery opens up the potential for more accessible precision medicine in analgesic usage, though further investigation is required to confirm these links and explore their implications fully.
Cite This Article
APA
Bacon EK, Donnelly CG, Bellone RR, Haase B, Finno CJ, Velie BD.
(2024).
Preliminary investigation of potential links between pigmentation variants and opioid analgesic effectiveness in horses during cerebrospinal fluid centesis.
BMC Vet Res, 20(1), 311.
https://doi.org/10.1186/s12917-024-04139-z Publication
Researcher Affiliations
- Equine Genetics and Genomics Group, School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia. elouise.bacon@sydney.edu.au.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithica, NY, 14850, USA.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
- School of Veterinary Science, University of Sydney, Sydney, NSW, Australia.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
- Equine Genetics and Genomics Group, School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia.
MeSH Terms
- Animals
- Horses
- Analgesics, Opioid / pharmacology
- Analgesics, Opioid / therapeutic use
- Receptor, Melanocortin, Type 1 / genetics
- Polymorphism, Single Nucleotide
- Pigmentation / genetics
- Agouti Signaling Protein / genetics
- Male
- Female
- Phenotype
- Cerebrospinal Fluid / metabolism
Conflict of Interest Statement
Rebecca Bellone is affiliated with the UC Davis Veterinary Genetics Laboratory that offers genetic testing in horses and other species, including testing for MC1R.
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