Antinociceptive and respiratory effects following application of transdermal fentanyl patches and assessment of brain μ-opioid receptor mRNA expression in ball pythons

• Autores: Rima J. Kharbush, Allison Gutwillig, Kate Hartzler, Rebecca S. Kimyon, Alyssa N. Gardner, Andrew D. Abbott, Sherry K. Cox, Jyoti J. Watters, Kurt K. Sladky, Stephen M. Johnson
• Localización: American Journal of Veterinary Research, ISSN-e 1943-5681, ISSN 0002-9645, Vol. 78, Nº. 7, 2017, págs. 785-795
• Idioma: inglés
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• Resumen

  • OBJECTIVE To quantify plasma fentanyl concentrations (PFCs) and evaluate antinociceptive and respiratory effects following application of transdermal fentanyl patches (TFPs) and assess cerebrospinal μ-opioid receptor mRNA expression in ball pythons (compared with findings in turtles).

    ANIMALS 44 ball pythons (Python regius) and 10 turtles (Trachemys scripta elegans).

    PROCEDURES To administer 3 or 12 μg of fentanyl/h, a quarter or whole TFP (TFP-3 and TFP-12, respectively) was used. At intervals after TFP-12 application in snakes, PFCs were measured by reverse-phase high-pressure liquid chromatography. Infrared heat stimuli were applied to the rostroventral surface of snakes to determine thermal withdrawal latencies after treatments with no TFP (control [n = 16]) and TFP-3 (8) or TFP-12 (9). Breathing frequency was measured in unrestrained controls and TFP-12–treated snakes. μ-Opioid receptor mRNA expression in brain and spinal cord tissue samples from snakes and turtles (which are responsive to μ-opioid receptor agonist drugs) were quantified with a reverse transcription PCR assay.

    RESULTS Mean PFCs were 79, 238, and 111 ng/mL at 6, 24, and 48 hours after TFP-12 application, respectively. At 3 to 48 hours after TFP-3 or TFP-12 application, thermal withdrawal latencies did not differ from pretreatment values or control treatment findings. For TFP-12–treated snakes, mean breathing frequency significantly decreased from the pretreatment value by 23% and 41% at the 24- and 48-hour time points, respectively. Brain and spinal cord tissue μ-opioid receptor mRNA expressions in snakes and turtles did not differ.

    CONCLUSIONS AND CLINICAL RELEVANCE In ball pythons, TFP-12 application resulted in high PFCs, but there was no change in thermal antinociception, indicating resistance to μ-opioid-dependent antinociception in this species.