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

作者：Kharbush Rima J; Gutwillig Allison; Hartzler Kate E; Kimyon Rebecca S; Gardner Alyssa N; Abbott Andrew D; Cox Sherry K; Watters Jyoti J; Sladky Kurt K; Johnson Stephen M^*

来源：AJVR: American Journal of Veterinary Research , 2017, 78(7): 785-795.

DOI：10.2460/ajvr.78.7.785

OBJECTIVE
To quantify plasma fentanyl concentrations (PFCs) and evaluate antinociceptive and respiratory effects following application of transdermal fentanyl patches (TFPs) and assess cerebrospinal mu-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 mu g 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. mu-Opioid receptor mRNA expression in brain and spinal cord tissue samples from snakes and turtles (which are responsive to mu-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 mu-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 mu-opioid-dependent antinociception in this species.

• 出版日期2017-7