TY - JOUR

T1 - The Use of Zebrafish as a Non-traditional Model Organism in Translational Pain Research: The Knowns and the Unknowns

AU - Costa, Fabiano V.

AU - Rosa, Luiz V.

AU - Quadros, Vanessa A.

AU - de Abreu, Murilo S.

AU - Santos, Adair R.S.

AU - Sneddon, Lynne U.

AU - Kalueff, Allan V.

AU - Rosemberg, Denis B.

N1 - Funding Information: F.V.C., V.A.Q., and L.C.R. received CAPES fellowship. D.B.R. and A.R.S. are recipients of CNPq research productivity grant. D.B.R. research is also supported by PROEX/CAPES (process number 23038.005450/2020-19) and Programa PQ-Ga?cho FAPERGS (process number 19/2551-0001764-2) fellowship grants. A.V.K. is the Chair of the International Zebrafish Neuroscience Research Con sortium (ZNRC). His research is supported by the Russian Science Foundation (RSF) grant 20-65-46006. L.U.S. is convenor of the FELASA working group producing a report on Pain Management in Zebrafish and is a member of the NC3Rs (UK) expert panel on zebrafish welfare. The funders did not influence writing and submission of this manuscript. Funding Information: The authors thank the financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-Finance Code 001, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS). AVK collaboration is supported by Sirius University, Sochi, Russia. Publisher Copyright: © 2022 Bentham Science Publishers.

PY - 2022/3

Y1 - 2022/3

N2 - The ability of the nervous system to detect a wide range of noxious stimuli is crucial to avoid life-threatening injury and to trigger protective behavioral and physiological responses. Pain represents a complex phenomenon, including nociception associated with cognitive and emotional processing. Animal experimental models have been developed to understand the mechanisms involved in pain response, as well as to discover novel pharmacological and non-pharmacological anti-pain therapies. Due to the genetic tractability, similar physiology, low cost, and rich behavioral repertoire, the zebrafish (Danio rerio) is a powerful aquatic model for modeling pain responses. Here, we summarize the molecular machinery of zebrafish responses to painful stimuli, as well as emphasize how zebrafish-based pain models have been successfully used to understand specific molecular, physiological, and behavioral changes following different algogens and/or noxious stimuli (e.g., acetic acid, formalin, histamine, Complete Freund's Adjuvant, cinnamaldehyde, allyl isothiocyanate, and fin clipping). We also discuss recent advances in zebrafish-based studies and outline the potential advantages and limitations of the existing models to examine the mechanisms underlying pain responses from evolutionary and translational perspectives. Finally, we outline how zebrafish models can represent emergent tools to explore pain behaviors and pain-related mood disorders, as well as to facilitate analgesic therapy screening in translational pain research.

AB - The ability of the nervous system to detect a wide range of noxious stimuli is crucial to avoid life-threatening injury and to trigger protective behavioral and physiological responses. Pain represents a complex phenomenon, including nociception associated with cognitive and emotional processing. Animal experimental models have been developed to understand the mechanisms involved in pain response, as well as to discover novel pharmacological and non-pharmacological anti-pain therapies. Due to the genetic tractability, similar physiology, low cost, and rich behavioral repertoire, the zebrafish (Danio rerio) is a powerful aquatic model for modeling pain responses. Here, we summarize the molecular machinery of zebrafish responses to painful stimuli, as well as emphasize how zebrafish-based pain models have been successfully used to understand specific molecular, physiological, and behavioral changes following different algogens and/or noxious stimuli (e.g., acetic acid, formalin, histamine, Complete Freund's Adjuvant, cinnamaldehyde, allyl isothiocyanate, and fin clipping). We also discuss recent advances in zebrafish-based studies and outline the potential advantages and limitations of the existing models to examine the mechanisms underlying pain responses from evolutionary and translational perspectives. Finally, we outline how zebrafish models can represent emergent tools to explore pain behaviors and pain-related mood disorders, as well as to facilitate analgesic therapy screening in translational pain research.

KW - Anti-pain medication screening

KW - Nociceptors

KW - Non-traditional pain models

KW - Noxious stimuli

KW - Pain-related behaviors

KW - Zebrafish

KW - Animals

KW - Analgesics

KW - Zebrafish/genetics

KW - Pain/drug therapy

KW - Translational Research, Biomedical

KW - Disease Models, Animal

UR - http://www.scopus.com/inward/record.url?scp=85126831080&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/acfb71d4-1506-39b6-9221-03ebf1628c58/

U2 - 10.2174/1570159X19666210311104408

DO - 10.2174/1570159X19666210311104408

M3 - Review article

C2 - 33719974

AN - SCOPUS:85126831080

VL - 20

SP - 476

EP - 493

JO - Current Neuropharmacology

JF - Current Neuropharmacology

SN - 1570-159X

IS - 3

ER -