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

Rima J. Kharbush Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Allison Gutwillig Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Kate E. Hartzler Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Rebecca S. Kimyon Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Alyssa N. Gardner Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Andrew D. Abbott Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Sherry K. Cox Department of Comparative Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

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Jyoti J. Watters Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Kurt K. Sladky Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Stephen M. Johnson Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Abstract

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.

Abstract

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.

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