{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:28:00Z","timestamp":1773008880702,"version":"3.50.1"},"reference-count":75,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT\/MCTES\u2014Portuguese Foundation for Science and Technology\/Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]},{"name":"2021.00458.CEECIND","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>In the last decade, a considerable number of studies have broadened our knowledge of the nociceptive mechanisms of pain, a global health problem in both humans and animals. The use of herbal compounds such as eugenol, menthol, thymol, and carvacrol as analgesic agents has accompanied the growing interest in this area, offering a possible solution for this complex problem. Here, we aimed to explore how these natural substances\u2014at three different concentrations (2, 5 and 10 mg\/L)\u2014affect the pain responses in zebrafish (Danio rerio) larvae exposed to 0.05% acetic acid (AA) for 1 min. By analysing the activity of acetylcholinesterase (AChE), 5\u2032-ectonucleotidase and NTPDases, as well as aversion and exploratory behaviours, it was observed that that although all substances were effective in counteracting the pain stimulus, the concentration range within which they do so might be very limited. Eugenol, despite its acknowledged properties in fish anaesthesia, failed to alleviate the pain stimulus at low concentrations. Contrastingly, menthol exhibited the most promising results at the lowest concentrations tested. Overall, it is concluded that menthol might be a good analgesic for this species, qualifying it as a substance of interest for prospective studies.<\/jats:p>","DOI":"10.3390\/ph17040457","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T09:36:54Z","timestamp":1712050614000},"page":"457","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Antinociceptive Analysis of Natural Monoterpenes Eugenol, Menthol, Carvacrol and Thymol in a Zebrafish Larval Model"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0322-9489","authenticated-orcid":false,"given":"Cl\u00e1udia Alexandra","family":"Rocha","sequence":"first","affiliation":[{"name":"School of Life and Environmental Sciences, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9870-6666","authenticated-orcid":false,"given":"Lu\u00eds M.","family":"F\u00e9lix","sequence":"additional","affiliation":[{"name":"Centre for the Research and Technology of Agro-Environment and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"},{"name":"Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4026-5965","authenticated-orcid":false,"given":"Sandra Mariza","family":"Monteiro","sequence":"additional","affiliation":[{"name":"School of Life and Environmental Sciences, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"},{"name":"Centre for the Research and Technology of Agro-Environment and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"},{"name":"Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3880-3442","authenticated-orcid":false,"given":"Carlos","family":"Ven\u00e2ncio","sequence":"additional","affiliation":[{"name":"Centre for the Research and Technology of Agro-Environment and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"},{"name":"Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"},{"name":"Department of Animal Science, School of Agrarian and Veterinary Sciences, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"},{"name":"Veterinary and Animal Research Centre (CECAV), Associate Laboratory of Animal and Veterinary Sciences (AL4AnimalS), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1098\/rstb.2019.0276","article-title":"Persistence of pain in humans and other mammals","volume":"374","author":"Williams","year":"2019","journal-title":"Philos. 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