Predicting morphine related side effects in the ED: An international cohort study

Bounes, Vincent; Charriton-Dadone, B.; Levraut, J.; Delangue, Cyril; Carpentier, F.; Mary-Chalon, Stéphanie; Houzé-Cerfon, Vanessa; Sommet, Agnès; Houzé-Cerfon, Charles-Henri; Ganetsky, Michael

doi:10.1016/j.ajem.2016.11.053

Cited by 11 publications

(9 citation statements)

References 22 publications

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“…Despite increased knowledge of the different activities of morphine, little is known about how dosing regimens affect the manifestation of motor behavioral effects. Euphoria, lethargy, or drowsiness are very common clinical side effects of morphine [ 22 , 23 ] and are mirrored by morphine-induced hypoactivity reported in rodents [ 24 ]. The relationship between the behavioral effects of morphine, antinociceptive tolerance, and morphine dosing has been elusive, mainly due to reported inconsistencies in experimental results, which are likely the consequence of different experimental approaches with regards to the route of administration, formulation of morphine, type of animals used, as well as treatment protocols (dose, frequency, or duration of treatment) [ 9 , 10 , 12 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats

2021

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Efficient repetitive clinical use of morphine is limited by its numerous side effects, whereas analgesic tolerance necessitates subsequent increases in morphine dose to achieve adequate levels of analgesia. While many studies focused on analgesic tolerance, the effect of morphine dosing on non-analgesic effects has been overlooked. This study aimed to characterize morphine-induced behavior and the development and progression of morphine-induced behavioral tolerance. Adult male Sprague–Dawley rats were repetitively treated with subcutaneous morphine for 14 days in two dose groups (A: 5 mg/kg/day (b.i.d.) → 10 mg/kg/day; B: 10 mg/kg/day (b.i.d.) → 20 mg/kg/day). Motor behavior was assessed daily (distance traveled, speed, moving time, rearing, rotation) in an open-field arena, before and 30 min post-injections. Antinociception was measured using tail-flick and hot-plate assays. All measured parameters were highly suppressed in both dosing groups on the first treatment day, followed by a gradual manifestation of behavioral tolerance as the treatment progressed. Animals in the high-dose group showed increased locomotor activity after 10 days of morphine treatment. This excitatory phase converted to an inhibition of behavior when a higher morphine dose was introduced. We suggest that the excitatory locomotor effects of repetitive high-dose morphine exposure represent a signature of its behavioral and antinociceptive tolerance.

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Section: Discussionmentioning

confidence: 99%

Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats

2021

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“…Rearing activity is thought to be a reliable parameter to assess exploratory behaviour [ 50 , 85 , 91 ], which is why the suppressed rearing in response to repeated morphine exposure in the present study indicates reduced exploratory behaviour, as reported previously [ 92 ]. This effect was interpreted to reflect morphine-induced clinical sedation or drowsiness [ 84 , 88 , 93 , 94 ]. Morphine-induced reduced rearing could also be a result of drug-induced anxiety-like or depressive-like behaviour.…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of a Novel Opioid Ligand UTA1003 on Antinociceptive Tolerance and Motor Behaviour

et al. 2022

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Analgesic tolerance is a major problem in the clinic for the maintenance of opioid-induced long-term pain relief. Opioids with mixed activity on multiple opioid receptors promise reduced antinociceptive tolerance in preclinical studies, but these compounds typically show poor bioavailability upon oral, subcutaneous, intraperitoneal, or intravenous administration. We designed UTA1003 as a novel opioid that acts as a mu (MOP) and kappa (KOP) opioid receptor agonist and a partial agonist for delta (DOP) opioid receptor. In the present study, its antinociceptive effects, as well as its effects on antinociceptive tolerance and motor behaviour, were investigated in male rats. Acute antinociception was measured before (basal) and at different time points after subcutaneous injection of UTA1003 or morphine using the tail flick and hot plate assays. Various motor behavioural activities, including horizontal locomotion, rearing, and turning, were automatically measured in an open-field arena. The antinociceptive and behavioural effects of repeated administration of UTA1003 and morphine were determined over eight days. UTA1003 induced mild antinociceptive effects after acute administration but induced no tolerance after repeated treatment. Importantly, UTA1003 co-treatment with morphine prevented antinociceptive tolerance compared to morphine alone. UTA1003 showed less motor suppression than morphine in both acute and sub-chronic treatment regimens, while it did not affect morphine-induced motor suppression or hyper-excitation. Based on these activities, we speculate that UTA1003 crosses the blood-brain barrier after subcutaneous administration and, therefore, could be developed as a lead molecule to avoid opioid-induced antinociceptive tolerance and motor suppression. Further structural modifications to improve its antinociceptive effects, toxicity profile, and ADME parameters are nevertheless required.

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“…Both studies reported similar adverse events including nausea, vomiting and dizziness. Due to rare but unpredictable serious adverse events (42), patients require lengthy monitoring post IV administration of morphine resulting in potentially higher EDLOS than that of other analgesia. Unfortunately, neither studies included EDLOS as an outcome measure making it impossible to determine this.…”

Section: Opioidsmentioning

confidence: 99%

The therapeutic management of back pain with and without sciatica in the emergency department: a systematic review

Ashbrook

Rogdakis²,

Callaghan

et al. 2020

Physiotherapy

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Predicting morphine related side effects in the ED: An international cohort study

Cited by 11 publications

References 22 publications

Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats

Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats

Differential Effects of a Novel Opioid Ligand UTA1003 on Antinociceptive Tolerance and Motor Behaviour

The therapeutic management of back pain with and without sciatica in the emergency department: a systematic review

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