Is there a genetic basis for the variable response to opioids in cats? A pilot study.

Variable responses to opioids are recognised in many species (Taylor et al. 2007). The study aimed to probe the underlying genetic contribution to antinociceptive phenotype following opioid administration to cats. The 5 exons of the mu opioid receptor (MOPR) gene were amplified from blood gDNA by PCR and subjected to DNA sequencing for 12 laboratory cats for whom historical thermal threshold data recorded after administration of four opioids were available (Slingsby et al. 2012). Fisher’s exact test and descriptive statistics were applied. A single synonymous mutation (A>G) was found in exon 2 together with other single nucleotide polymorphisms (SNPs) and insertion/deletions throughout the other exons. There were SNPs that could affect mRNA or protein expression in the promoter and untranslated regions of the MOPR. A SNP was also identified in intron 4 that may affect mRNA splicing. Combined, these SNPs formed two haplotypes, with 4 cats (group A) being genetically distinct from the remainder (group B). Peak thermal threshold (PTT), time to peak (Tmax), area under the temperature-time curve (AUC) and the proportion of each group reaching cut out (55ºC) in each group were compared. For group A cats fentanyl, PTT and AUC were higher and less variable than group B, whereas Tmax was higher and more variable. For butorphanol, group A PTT and AUC results were lower and more variable whereas Tmax was higher and more variable. Differences between groups A and B for buprenorphine and methadone were less pronounced. There were no significant differences between groups A and B in the proportion reaching cut out. This is first description of any genetic basis of variable response to opioids in cats. Future work should focus on the downstream consequences of this mutant haplotype in order to understand its contribution towards difficulties in pain control for individual cats. This work was supported with a grant from the Feline Advisory Bureau (now called International Cat Care) Slingsby LS, Murrell JC, Taylor PM (2012) Buprenorphine in combination with naloxone at a ratio of 15:1 does not enhance antinociception from buprenorphine in healthy cats. The Veterinary Journal 192, 523-524. Taylor P, Slingsby L, Pypendop B et al. (2007) Variable response to opioid analgesia in cats. Vet Anaesth Analg 34, 6-7.