PAIN STUDIES IN ZEBRAFISH (DANIO RERIO) MODEL, CURRERNT METHODS AND ANIMAL WELFARE PRACTICES

Yıl 2025, Cilt: 16 Sayı: 1, 1 - 8, 05.05.2025

Semi Sertaç Bağırsakçı , Ender Yarsan

https://doi.org/10.38137/vftd.1537594

Öz

Zebrafish (Danio rerio) is a model organism that has been frequently used in biomedical research in recent years and its use is increasing day by day. The fact that zebrafish has a close relationship with human genes causes regeneration modelling, transgenic modelling, toxicity studies, behavioural studies, cancer modelling, disease modelling and is frequently preferred today. It is inevitable that newly discovered chemicals or chemicals with unknown effects should be tested in model organisms. In this context, zebrafish are used to investigate pain mechanisms and to synthesise new compounds or drugs by elucidating these mechanisms. During the studies, the 3R principle (Replacment, Reduction, Refinement) should be taken into consideration and the welfare conditions of the fish should be provided in the best way until the end of the experiment (transport, quarantine, care-feeding, environmental conditions, termination of the experiment). Within the scope of this review, it is aimed to provide information on pain studies in zebrafish model, current methods used, pain management and drugs used, and applications necessary to ensure the welfare of fish.

Anahtar Kelimeler

Danio rerio, pain, welfare, zebrafish

ZEBRA BALIĞI (DANIO RERIO) MODELİNDE AĞRI ÇALIŞMALARI, GÜNCEL YÖNTEMLER VE HAYVAN REFAHI UYGULAMALARI

Öz

Zebra balığı (Danio rerio) son yıllarda biyomedikal araştırmalarda sıklıkla kullanılan ve kullanımı gün geçtikçe artan bir model organizmadır. Zebra balığının insan genleri ile yakın bir ilişkiye sahip olması rejenerasyon modellemeleri, transgenik modellemeler, toksisite çalışmaları, davranış çalışmaları, kanser modellemeleri, hastalık modellemeleri oluşturulmasına ve günümüzde sıkça tercih edilmesine sebep olmaktadır. Yeni keşfedilen veya etkileri bilinmeyen kimyasal maddelerin model organizmalarda denenmesi kaçınılmazdır. Bu kapsamda zebra balıkları ağrı mekanizmalarını araştırmada ve bu mekanizmaların aydınlatılması ile yeni bileşik veya ilaçların sentezlenmesinde kullanılmaktadır. Yapılan çalışmalar esnasında 3R prensibi (Replacment, Reduction, Refinement) göz önüne alınarak balıkların deney sonlandırılmasına kadar geçen süreçte (taşıma, karantina, bakım-besleme, ortam koşulları, deney sonlandırılması) refah koşullarının en iyi şekilde sağlanması gereklidir. Bu derleme kapsamında; ağrı çalışmalarında zebra balığı modeli, kullanılan güncel yöntemler, ağrının yönetimi ve kullanılan ilaçlar ile balıkların refahının sağlanması için gerekli olan uygulamalara yönelik bilgiler sunulmuştur.

Anahtar Kelimeler

Ağrı, Danio rerio, Refah, Zebra balığı

Kaynakça

• Adedara, I. A., Costa, F. V., Biasuz, E., Canzian, J., Farombi, E. O. & Rosemberg, D. B. (2022). Influence of acid-sensing ion channel blocker on behavioral responses in a zebrafish model of acute visceral pain. Behavioural Brain Research, 416, 113565.
• Alvarez, F. A., Rodriguez-Martin, I., Gonzalez-Nuñez, V., Marrón Fernández de Velasco, E., Gonzalez Sarmiento, R. & Rodríguez, R. E. (2006). New kappa opioid receptor from zebrafish Danio rerio. Neuroscience Letters, 405(1-2), 94–99.
• Barrallo, A., González-Sarmiento, R., Alvar, F. & Rodríguez, R. E. (2000). ZFOR2, a new opioid receptor-like gene from the teleost zebrafish (Danio rerio). Brain Research. Molecular Brain Research, 84(1-2), 1–6.
• Basavarajappa, B. S., Shivakumar, M., Joshi, V. & Subbanna, S. (2017). Endocannabinoid system in neurodegenerative disorders. Journal of Neurochemistry, 142(5), 624–648.
• Beyaz, S. & Aslan, A. (2018). Optogenetik. Yüzüncü Yıl Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 23(2), 182-191.
• Cartner, S. C., Durboraw, E. & Watts, A. (2020). Regulations, policies and guidelines pertaining to the use of zebrafish in biomedical research. In: The Zebrafish in Biomedical Research (pp. 451-459). Academic Press.
• Cassar, S., Adatto, I., Freeman, J. L., Gamse, J. T., Iturria, I., Lawrence, C., Muriana, A., Peterson, R. T., Van Cruchten, S. & Zon, L. I. (2020). Use of Zebrafish in Drug Discovery Toxicology. Chemical Research in Toxicology, 33(1), 95–118.
• Chatigny, F., Creighton, C. M. & Stevens, E. D. (2018). Updated Review of Fish Analgesia. Journal of the American Association for Laboratory Animal Science: JAALAS, 57(1), 5–12.
• Chu Sin Chung, P. & Kieffer, B. L. (2013). Delta opioid receptors in brain function and diseases. Pharmacology & Therapeutics, 140(1), 112–120.
• Collymore, C. (2020). Anesthesia, analgesia, and euthanasia of the laboratory zebrafish. In: The Zebrafish in Biomedical Research (pp. 403-413). Academic Press.
• Collymore, C., Banks, E. K. & Turner, P. V. (2016). Lidocaine hydrochloride compared with MS222 for the euthanasia of zebrafish (Danio rerio). Journal of the American Association for Laboratory Animal Science, 55(6), 816-820.
• Costa, F. V., Rosa, L. V., Quadros, V. A., de Abreu, M. S., Santos, A. R. S., Sneddon, L. U., Kalueff, A. V. & Rosemberg, D. B. (2022). The Use of Zebrafish as a Non-traditional Model Organism in Translational Pain Research: The Knowns and the Unknowns. Current neuropharmacology, 20(3), 476–493.
• Costa, F. V., Rosa, L. V., Quadros, V. A., Santos, A. R. S., Kalueff, A. V. & Rosemberg, D. B. (2019). Understanding nociception-related phenotypes in adult zebrafish: Behavioral and pharmacological characterization using a new acetic acid model. Behavioural Brain Research, 359, 570–578.
• Deakin, A. G., Buckley, J., AlZu'bi, H. S., Cossins, A. R., Spencer, J. W., Al'Nuaimy, W., Young, I. S., Thomson, J. S. & Sneddon, L. U. (2019). Automated monitoring of behaviour in zebrafish after invasive procedures. Scientific Reports, 9(1), 9042.
• Dhanasiri, A. K., Fernandes, J. M. & Kiron, V. (2013). Acclimation of zebrafish to transport stress. Zebrafish, 10(1), 87–98.
• Galindo-Villegas, J. (2020). The zebrafish disease and drug screening model: A strong ally against Covid-19. Frontiers in Pharmacology, 11, 680.
• Gau, P., Poon, J., Ufret-Vincenty, C., Snelson, C. D., Gordon, S. E., Raible, D. W. & Dhaka, A. (2013). The zebrafish ortholog of TRPV1 is required for heat-induced locomotion. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 33(12), 5249–5260.
• Gonzalez-Nunez, V. & Rodríguez, R. E. (2009). The zebrafish: a model to study the endogenous mechanisms of pain. ILAR Journal, 50(4), 373–386.
• Ibrahim, M. M., Porreca, F., Lai, J., Albrecht, P. J., Rice, F. L., Khodorova, A., Davar, G., Makriyannis, A., Vanderah, T. W., Mata, H. P. & Malan, T. P., Jr (2005). CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids. Proceedings of the National Academy of Sciences of the United States of America, 102(8), 3093–3098.
• Ibsen, M. S., Connor, M. & Glass, M. (2017). Cannabinoid CB1 and CB2 receptor signaling and bias. Cannabis and Cannabinoid Research, 2(1), 48-60.
• Khan, F. R. & Alhewairini, S. (2018). Zebrafish (Danio rerio) as a model organism. Current Trends in Cancer Management, 27, 3-18.
• Köhler, A., Collymore, C., Finger-Baier, K., Geisler, R., Kaufmann, L., Pounder, K. C., Schulte-Merker, S., Valentim, A., Varga, Z. M., Weiss, J. & Strähle, U. (2017). Report of Workshop on Euthanasia for Zebrafish-A Matter of Welfare and Science. Zebrafish, 14(6), 547–551.
• Krug, R. G. & Clark, K. J. (2015). Elucidating cannabinoid biology in zebrafish (Danio rerio). Gene, 570(2), 168–179.
• Leite, G. O., Santos, S. A. A. R., Ribeiro, A. D. D. C., Bezerra, F. M. D. H. & Campos, A. R. (2021). Impact of sex and environmental conditions on the responses to pain in zebrafish. BrJP, 4(1), 9-14.
• Lieggi, C. (2020). Importation and quarantine. The Zebrafish in Biomedical Research, 431-442.
• Lingueglia E. (2007). Acid-sensing ion channels in sensory perception. The Journal of Biological Chemistry, 282(24), 17325–17329.
• Lopez-Luna, J., Al-Jubouri, Q., Al-Nuaimy, W. & Sneddon, L. U. (2017). Reduction in activity by noxious chemical stimulation is ameliorated by immersion in analgesic drugs in zebrafish. The Journal of Experimental Biology, 220(Pt 8), 1451–1458.
• Luchtenburg, F. J., Schaaf, M. J. M. & Richardson, M. K. (2019). Functional characterization of the cannabinoid receptors 1 and 2 in zebrafish larvae using behavioral analysis. Psychopharmacology, 236(7), 2049–2058.
• Madelaine, R., Lovett-Barron, M., Halluin, C., Andalman, A. S., Liang, J., Skariah, G. M., Leung, L. C., Burns, V. M. & Mourrain, P. (2017). The hypothalamic NPVF circuit modulates ventral raphe activity during nociception. Scientific Reports, 7, 41528.
• Magalhães, F. E. A., de Sousa, C. Á. P. B., Santos, S. A. A. R., Menezes, R. B., Batista, F. L. A., Abreu, Â. O., de Oliveira, M. V., Moura, L. F. W. G., Raposo, R. D. S. & Campos, A. R. (2017). Adult Zebrafish (Danio rerio): An Alternative Behavioral Model of Formalin-Induced Nociception. Zebrafish, 14(5), 422–429.
• Malafoglia, V., Bryant, B., Raffaeli, W., Giordano, A. & Bellipanni, G. (2013). The zebrafish as a model for nociception studies. Journal of Cellular Physiology, 228(10), 1956–1966.
• Marron Fdez de Velasco, E., Law, P. Y. & Rodríguez, R. E. (2009). Mu opioid receptor from the zebrafish exhibits functional characteristics as those of mammalian mu opioid receptor. Zebrafish, 6(3), 259–268.
• Martins, T., Valentim, A. M., Pereira, N. & Antunes, L. M. (2016). Anaesthesia and analgesia in laboratory adult zebrafish: a question of refinement. Laboratory Animals, 50(6), 476–488.
• Marwaha, L., Bansal, Y., Singh, R., Saroj, P., Bhandari, R. & Kuhad, A. (2016). TRP channels: potential drug target for neuropathic pain. Inflammopharmacology, 24(6), 305–317.
• Matthews, M., Trevarrow, B. & Matthews, J. (2002). A virtual tour of the Guide for zebrafish users. Lab Animal, 31(3), 34–40.
• Matthews, M. & Varga, Z. M. (2012). Anesthesia and euthanasia in zebrafish. ILAR Journal, 53(2), 192–204. Ohnesorge, N., Heinl, C. & Lewejohann, L. (2021). Current Methods to Investigate Nociception and Pain in Zebrafish. Frontiers in Neuroscience, 15, 632634.
• Patton, E. E., Zon, L. I. & Langenau, D. M. (2021). Zebrafish disease models in drug discovery: from preclinical modelling to clinical trials. Nature Reviews Drug Discovery, 20(8), 611-628.
• Prober, D. A., Zimmerman, S., Myers, B. R., McDermott, B. M., Jr, Kim, S. H., Caron, S., Rihel, J., Solnica-Krezel, L., Julius, D., Hudspeth, A. J. & Schier, A. F. (2008). Zebrafish TRPA1 channels are required for chemosensation but not for thermosensation or mechanosensory hair cell function. The Journal Of Neuroscience: The Official Journal Of The Society For Neuroscience, 28(40), 10102–10110.
• Reilly, S. C., Quinn, J. P., Cossins, A. R. & Sneddon, L. U. (2008). Behavioural analysis of a nociceptive event in fish: Comparisons between three species demonstrate specific responses. Applied Animal Behaviour Science, 114(1-2), 248-259.
• Rodriguez-Martin, I., Herrero-Turrion, M. J., Marron Fdez de Velasco, E., Gonzalez-Sarmiento, R. & Rodriguez, R. E. (2007). Characterization of two duplicate zebrafish Cb2-like cannabinoid receptors. Gene, 389(1), 36–44.
• Saito, S. & Shingai, R. (2006). Evolution of thermoTRP ion channel homologs in vertebrates. Physiological Genomics, 27(3), 219-230.
• Schroeder, P. G. & Sneddon, L. U. (2017). Exploring the efficacy of immersion analgesics in zebrafish using an integrative approach. Applied Animal Behaviour Science, 187, 93-102. Sloman, K. A., Bouyoucos, I. A., Brooks, E. J. & Sneddon, L. U. (2019). Ethical considerations in fish research. Journal Of Fish Biology, 94(4), 556–577.
• Sneddon L. U. (2019). Evolution of nociception and pain: evidence from fish models. Philosophical Transactions Of The Royal Society Of London. Series B, Biological Sciences, 374(1785), 20190290.
• Taylor, J. C., Dewberry, L. S., Totsch, S. K., Yessick, L. R., DeBerry, J. J., Watts, S. A. & Sorge, R. E. (2017). A novel zebrafish-based model of nociception. Physiology & Behavior, 174, 83–88.
• Thomson, J. S., Al-Temeemy, A. A., Isted, H., Spencer, J. W. & Sneddon, L. U. (2019). Assessment of behaviour in groups of zebrafish (Danio rerio) using an intelligent software monitoring tool, the chromatic fish analyser. Journal Of Neuroscience Methods, 328, 108433.
• Underwood, W. & Anthony, R. (2020). AVMA guidelines for the euthanasia of animals: 2020 edition. Retrieved on March, 2013(30), 2020-1.
• Valentino, R. J. & Volkow, N. D. (2018). Untangling the complexity of opioid receptor function. Neuropsychopharmacology: Official Publication Of The American College Of Neuropsychopharmacology, 43(13), 2514–2520.
• Vargas, R. (2018). Anesthesiology, anesthetics and zebrafish (Danio Rerio). an animal model to perform basic biomedical research. EC Anaesth, 4, 202-213.
• von Krogh, K., Higgins, J., Saavedra Torres, Y. & Mocho, J. P. (2021). Screening of Anaesthetics in Adult Zebrafish (Danio rerio) for the Induction of Euthanasia by Overdose. Biology, 10(11), 1133.
• Wilson, R. I. & Nicoll, R. A. (2002). Endocannabinoid signaling in the brain. Science (New York, N.Y.), 296(5568), 678–682.
• Wong, D., von Keyserlingk, M. A., Richards, J. G. & Weary, D. M. (2014). Conditioned place avoidance of zebrafish (Danio rerio) to three chemicals used for euthanasia and anaesthesia. Plos One, 9(2), e88030.
• Yağcı, Ü. & Saygin, M. (2019). Ağrı fizyopatolojisi. Medical Journal of Süleyman Demirel University, 26(2), 209-220.