High and Hyper: Fentanyl Induces Psychomotor Side-Effects in Healthy Pigs

Abstract

Analgesic effects of fentanyl have been investigated using behavior. The behavioral effects of fentanyl and possible serotonergic influence are largely unknown. We therefore investigated behavioral effects of fentanyl, with or without the serotonin antagonist ketanserin, in pigs. Fourteen mixed-breed pigs, weighing 17–25 kg were included in a randomised blinded prospective, balanced three-group study. Ten pigs received first 5 and then 10 µg/kg of fentanyl intravenously. Ketanserin at 1 mg/kg or saline was given intravenously as a third injection. Four control pigs received three injections of saline. Behavior was video-recorded. The distance moved was automatically measured by commercially available software, and behaviors manually scored in retrospect. Fentanyl inhibited resting and playing, and induced different repetitive behaviors. The mean (SD) distance moved in the control group and fentanyl group was 21.3 (13.0) and 57.8 (20.8) metres respectively (p < 0.05 for pairwise comparison). A stiff gait pattern was seen after fentanyl injection for median (range) 4.2 (2.8–5.1) minutes per 10 min, which was reduced to 0 (0–4) s after ketanserin administration. Conclusion: fentanyl-induced motor and behavioral effects, and serotonergic transmission may be involved in some of them. The psychomotor side effects of fentanyl could potentially interfere with post-operative pain evaluation in pigs.

Effects of sub-lethal doses of fentanyl on vital physiologic functions and withdrawal-like behaviors in adult goats

“…Each of these behaviors were greatest at the beginning of the observation period and waned by 3-4h, where the duration of the increases in each behavior was dose-dependent. These behaviors are similar to that observed in rodents and pigs following abstinence (Varshneya et al, 2019;Digranes et al, 2023) or naloxone-precipitated withdrawal from fentanyl (Uddin et al, 2021), suggesting that the adult goat may also be a useful model to study mechanisms or other unique aspects of withdrawal from fentanyl and its relevance to human withdrawal symptomatology.…”

“…We tested the hypotheses that sublethal doses of opioids will induce both dose-and timedependent dysfunction in multiple physiologic functions, including breathing frequency suppression (OIRD), increased tonic (or phasic) activation of chest wall and upper airway respiratory muscles (WCS) leading to a delayed or lack of inspiratory flow, arterial hypertension, reduced heart rate, and reductions of reflexes such as sighs and swallows. We further hypothesize that fentanyl will also increase acute withdrawal-like behaviors in adult goats like those seen in small mammals and humans (Varshneya et al, 2019;Digranes et al, 2023). Data from sublethal fentanyl doses will be important to clinicians in decisions regarding use of opioids as an analgesic after surgery and in chronic conditions of persistent pain.…”

“…The mechanism(s) and timing of opioid-induced increases in the A-a O 2 gradient are less clear but have been shown to develop with a slower time course than OIRD ( Meyer et al, 2010 ; Getsy et al, 2022 ). Withdrawal symptoms manifest for hours after fentanyl use, and include symptoms such as hyperactivity, anxiety, and repetitive behaviors among others ( Varshneya et al, 2019 ; Digranes et al, 2023 ). Accordingly, there is a need for a better understanding of the timing and magnitude of fentanyl on multiple vital physiological functions and potential withdrawal-like behaviors, particularly in a large animal model and across a dose range of fentanyl that does not cause sustained apnea or death.…”