Abstract

Avian species have varying analgesic responses to opioid drugs. Some of this variability could be due to extrinsic factors such as administration route or dose. However, intrinsic factors such as gene expression or polymorphic differences in opioid receptors may be important components.ObjectivesThe objectives of this study were to determine the relative gene expression and polymorphisms present for mu and kappa opioid receptors (OPRM1 and OPRK1) in the cerebrum, brainstem, spinal cord, and footpad of cockatiels and pigeons.MethodsTissue biopsies were obtained from 11 adult cockatiels (6 male and 5 female) and 11 adult pigeons (6 male and 5 female). RNA was extracted and qPCR was performed to determine the level of gene expression for OPRM1 and OPRK1 relative to a reference gene phosphoglycerate kinase 1 (PGK1) using the ΔΔCt method. Sanger sequencing was performed to identify polymorphisms, if present.ResultsThere were higher expression levels of OPRM1 compared to OPRK1 in all tissues examined regardless of species (p < 0.001, FDR p < 0.001) Cockatiels had less OPRK1 expression in the cerebrum compared to pigeons (p = 0.005, FDR p = 0.004). Cockatiels had more OPRM1 expression in the brainstem (p = 0.045, FDR p = 0.029), but less OPRM1 expression in the footpad compared to pigeons (p = 0.029, FDR p = 0.021). No other significant differences in OPRM1 or OPRK1 expression were identified across species. Two missense polymorphisms were identified in OPRK1; none were found in OPRM1.ConclusionThe differential expression of opioid receptors between cockatiels and pigeons could have implications for variability in analgesic response between these two species.

Highlights

  • Opioids are a diverse group of drugs that modify the transmission and perception of pain in vertebrates

  • Two were predicted to be a missense mutation in opioid receptor kappa 1 (OPRK1) resulting in an amino acid change from methionine in pigeons to either valine or isoleucine in cockatiels (Supplementary Figure 2)

  • There were significantly higher expression levels of opioid receptor mu 1 (OPRM1) compared to OPRK1 in all tissues examined regardless of species (Table 2)

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Summary

Introduction

Opioids are a diverse group of drugs that modify the transmission and perception of pain in vertebrates. Three main classes of opioid receptors exist (mu, kappa, and delta), only drugs that act on mu and kappa receptors are frequently used in avian species (Hawkins and Paul-Murphy, 2011). The analgesic effects of opioids have a wide range of clinical efficacy depending on the avian species studied. Similar doses of hydromorphone that were not effective in cockatiels induced thermal antinociception in another avian species, American kestrels (Guzman et al, 2013). The current opioids recommended for cockatiels are kappa agonists based on studies in other psittacine species and anecdotal clinical evidence (Paul-Murphy et al, 1999, 2009a,b; Sladky et al, 2006; Guzman et al, 2011, 2017)

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