Antinociceptive effects of buprenorphine in zebrafish larvae: An alternative for rodent models to study pain and nociception?

Steenbergen, Peter J.; Bardine, Nabila

doi:10.1016/j.applanim.2013.12.001

Cited by 44 publications

(34 citation statements)

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“…Zebrafish larvae and embryos have long been used to assay environmental toxicants. 2,3,8,30 They have also made waves in neuroscience as models for vision, 7,9,21,37,49 threat response, 38 memory, 52 algesia, 6,14,44 and sleep. 35,39,43 In a rare example of bench-to-bedside, the FDA approved the drug lorcaserin as an antiepileptic, based mostly on evidence in zebrafish.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous analysis of neuroactive compounds in zebrafish

Myers-Turnbull

Taylor

Helsell

et al. 2020

Preprint

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Purpose: Compounds that act on the central nervous system (CNS) are crucial tools in drug discovery and neuroscience. To discover compounds with novel mechanisms of action, researchers have developed behavioral screens in larval zebrafish including various methods to identify and classify hit compounds. However, these methods typically do not admit intuitive numerical scores of screen performance. This study describes methods to classify compounds simultaneously in zebrafish and quantify screen performance.Methods: We collected randomized, highly replicated data for two sets of compounds: 16 quality-control (QC) compounds and a reference set of 648 known CNS ligands. Machine learning models were trained to discriminate between compound-induced phenotypes, compare performance between protocols, and detect hit compounds.Results: Classification accuracy on the QC set was 94.3%. In addition, 106 of 648 CNS ligands were identified as phenotypically active, and hits were enriched for dopaminergic and serotonergic targets. The raw data is included to facilitate replication and data mining.Significance: This study describes methods to evaluate behavioral phenotyping assays, which can be used to facilitate comparison and standardization of data within the zebrafish phenotyping community.

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Section: Introductionmentioning

confidence: 99%

Simultaneous analysis of neuroactive compounds in zebrafish

Myers-Turnbull

Taylor

Helsell

et al. 2020

Preprint

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“…The concentration of 0.01% of acetic acid was selected based on Lopez-Luna's experiment setup (Lopez-Luna et al, 2017b) for a similar pharmacological study including some behavioural studies. In the work of (Steenbergen & Bardine, 2014), they compared the levels of cyclooxygenase-2 (cox-2) in zebrafish larvae and found that activation of nociceptive pathways in a low-concentration acetic acid environment produced behavioural changes that were accompanied by changes in levels of cox-2. As the associated gene is involved in nociceptive processes (Bingham et al, 2006), it seems reasonable to say that the acid-induced behavioural changes can be attributed to nociception.…”

Section: Introductionmentioning

confidence: 99%

Quantification of the influence of drugs on zebrafish larvae swimming kinematics and energetics

Zhao

Xiao

et al. 2020

PeerJ

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The use of zebrafish larvae has aroused wide interest in the medical field for its potential role in the development of new therapies. The larvae grow extremely quickly and the embryos are nearly transparent which allows easy examination of its internal structures using fluorescent imaging techniques. Medical treatment of zebrafish larvae can directly influence its swimming behaviours. These behaviour changes are related to functional changes of central nervous system and transformations of the zebrafish body such as muscle mechanical power and force variation, which cannot be measured directly by pure experiment observation. To quantify the influence of drugs on zebrafish larvae swimming behaviours and energetics, we have developed a novel methodology to exploit intravital changes based on observed zebrafish locomotion. Specifically, by using an in-house MATLAB code to process the recorded live zebrafish swimming video, the kinematic locomotion equation of a 3D zebrafish larvae was obtained, and a customised Computational Fluid Dynamics tool was used to solve the fluid flow around the fish model which was geometrically the same as experimentally tested zebrafish. The developed methodology was firstly verified against experiment, and further applied to quantify the fish internal body force, torque and power consumption associated with a group of normal zebrafish larvae vs. those immersed in acetic acid and two neuroactive drugs. As indicated by our results, zebrafish larvae immersed in 0.01% acetic acid display approximately 30% higher hydrodynamic power and 10% higher cost of transport than control group. In addition, 500 μM diphenylhydantoin significantly decreases the locomotion activity for approximately 50% lower hydrodynamic power, whereas 100 mg/L yohimbine has not caused any significant influences on 5 dpf zebrafish larvae locomotion. The approach has potential to evaluate the influence of drugs on the aquatic animal’s behaviour changes and thus support the development of new analgesic and neuroactive drugs.

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“…Recent studies in rainbow trout and zebrafish have demonstrated a reduction in swimming activity when fish were administered a potentially painful stimulus, injection of acetic acid (Correia et al, 2011;Reilly et al, 2008). Recently, another method to test the noxious effects of acetic acid in larvae has been developed, using dilute concentrations of acetic acid in the tank water (Steenbergen and Bardine, 2014), ranging from 0.0025% to 0.025%. Despite the differences in the experimental procedures between the work of Steenbergen and Bardine (2014) and the present study [Steenbergen and Bardine (2014) did not report any settling period prior to treatment with acid and the exposure time to the acid was much lower at 3 min versus 10 min in the present study], their results agree with those of our experiment, which confirms that very low concentrations of acetic acid evoke an increase in the locomotor activity of the fish.…”

Section: Experiments 1: Impact Of Noxious Chemicals On Larval Behaviourmentioning

confidence: 99%

“…Recently, another method to test the noxious effects of acetic acid in larvae has been developed, using dilute concentrations of acetic acid in the tank water (Steenbergen and Bardine, 2014), ranging from 0.0025% to 0.025%. Despite the differences in the experimental procedures between the work of Steenbergen and Bardine (2014) and the present study [Steenbergen and Bardine (2014) did not report any settling period prior to treatment with acid and the exposure time to the acid was much lower at 3 min versus 10 min in the present study], their results agree with those of our experiment, which confirms that very low concentrations of acetic acid evoke an increase in the locomotor activity of the fish. This may reflect an escape response from a potentially harmful, noxious stimulus and represents a nociceptive reflex (Sneddon, 2015;Sneddon et al, 2014).…”

Section: Experiments 1: Impact Of Noxious Chemicals On Larval Behaviourmentioning

confidence: 99%

“…Most studies in adult fish use injection of dilute acid; however, Mettam et al (2012) demonstrated topical application of this chemical stimulated nociceptors on the face of trout, suggesting that any acidic compounds may excite skin nociceptors without any skin damage (below 2% acetic acid). The effect of different concentrations of acetic acid dissolved in water has recently been investigated in 5 dpf larval zebrafish (Steenbergen and Bardine, 2014) but this immersion approach is yet to be developed for other chemicals. Given the strong evidence that nociceptors respond to low pH using a variety of chemicals in both mammals (Carstens et al, 1998) and fish (Ashley et al, 2007;Sneddon, 2003), we hypothesized that the agents used in the present study may evoke a behavioural response that can be quantified.…”

Section: Introductionmentioning

confidence: 99%

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Reduction in activity by noxious chemical stimulation is ameliorated by immersion in analgesic drugs in zebrafish

López-Luna

Al-Jubouri

Al-Nuaimy

et al. 2017

Journal of Experimental Biology

101

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Research has recently demonstrated that larval zebrafish show similar molecular responses to nociception to those of adults. Our study explored whether unprotected larval zebrafish exhibited altered behaviour after exposure to noxious chemicals and screened a range of analgesic drugs to determine their efficacy to reduce these responses. This approach aimed to validate larval zebrafish as a reliable replacement for adults as well as providing a high-throughput means of analysing behavioural responses. Zebrafish at 5 days postfertilization were exposed to known noxious stimuli: acetic acid (0.01%, 0.1% and 0.25%) and citric acid (0.1%, 1% and 5%). The behavioural response of each was recorded and analysed using novel tracking software that measures time spent active in 25 larvae at one time. Subsequently, the efficacy of aspirin, lidocaine, morphine and flunixin as analgesics after exposure to 0.1% acetic acid was tested. Larvae exposed to 0.1% and 0.25% acetic acid spent less time active, whereas those exposed to 0.01% acetic acid and 0.1-5% citric acid showed an increase in swimming activity. Administration of 2.5 mg l −1 aspirin, 5 mg l −1 lidocaine and 48 mg l −1 morphine prevented the behavioural changes induced by acetic acid. These results suggest that larvae respond to a noxious challenge in a similar way to adult zebrafish and other vertebrates and that the effect of nociception on activity can be ameliorated by using analgesics. Therefore, adopting larval zebrafish could represent a direct replacement of a protected adult fish with a non-protected form in pain-and nociception-related research.

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Antinociceptive effects of buprenorphine in zebrafish larvae: An alternative for rodent models to study pain and nociception?

Cited by 44 publications

References 50 publications

Simultaneous analysis of neuroactive compounds in zebrafish

Simultaneous analysis of neuroactive compounds in zebrafish

Quantification of the influence of drugs on zebrafish larvae swimming kinematics and energetics

Reduction in activity by noxious chemical stimulation is ameliorated by immersion in analgesic drugs in zebrafish

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