Guillaume Reho, Yannick Menger, Yannick Goumon, Vincent Lelièvre, Hervé Cadiou
{"title":"刨齿动物痛觉的行为学和药理学特征","authors":"Guillaume Reho, Yannick Menger, Yannick Goumon, Vincent Lelièvre, Hervé Cadiou","doi":"10.3389/fnmol.2024.1368009","DOIUrl":null,"url":null,"abstract":"IntroductionPain mostly arises because specialized cells called nociceptors detect harmful or potentially harmful stimuli. In lower animals with less convoluted nervous system, these responses are believed to be purely nociceptive. Amongst invertebrate animal models, planarians are becoming popular in a wide range of pharmacological and behavioral studies beyond the field of regeneration. Recent publications led the way on pain studies by focusing on nociceptive behaviors such as the ‘scrunching’ gait displayed under various noxious stimuli, as opposed to the ‘gliding’ gait planarians usually adopt in normal conditions.MethodsIn this study, we adapted commonly used nociceptive tests to further explore nociception in planarians of the species <jats:italic>Girardia dorotocephala</jats:italic>. By using behavioral analysis in open fields and place preferences, we managed to set up chemical, thermal and mechanical nociceptive tests. We also adapted RNA interference protocols and explored the effects of knocking down TRPA1 ion channels, one of the main effectors of chemically and thermally-induced nociceptive responses in vertebrates.ResultsConsequently, we demonstrated the reliability of the scrunching gait in this planarian species, which they displayed in a dose-dependent manner when exposed to the irritant AITC. We also showed that suppressing the expression of TRPA1 ion channels completely suppressed the scrunching gait, demonstrating the involvement of TRPA1 nociceptors in this nociceptive reaction. Besides, we also explored the effects of two common analgesics that both displayed strong antinociceptive properties. First, morphine reduced the chemically-induced nociceptive scrunching gaits by more than 20% and shifted the <jats:inline-formula><mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\"><mml:mi>E</mml:mi><mml:msub><mml:mi>C</mml:mi><mml:mn>50</mml:mn></mml:msub></mml:math></jats:inline-formula> of the dose–response curve by approximately 10 μM. Secondly, the NSAID meloxicam drastically reduced chemically-induced scrunching by up to 60% and reduced heat avoidance in place preference tests.DiscussionThus, we managed to characterize both behavioral and pharmacological aspects of <jats:italic>G. dorotocephala</jats:italic>’s nociception, further developing the use of planarians as a replacement model in pain studies and more globally the study of invertebrate nociception.","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Behavioral and pharmacological characterization of planarian nociception\",\"authors\":\"Guillaume Reho, Yannick Menger, Yannick Goumon, Vincent Lelièvre, Hervé Cadiou\",\"doi\":\"10.3389/fnmol.2024.1368009\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"IntroductionPain mostly arises because specialized cells called nociceptors detect harmful or potentially harmful stimuli. In lower animals with less convoluted nervous system, these responses are believed to be purely nociceptive. Amongst invertebrate animal models, planarians are becoming popular in a wide range of pharmacological and behavioral studies beyond the field of regeneration. Recent publications led the way on pain studies by focusing on nociceptive behaviors such as the ‘scrunching’ gait displayed under various noxious stimuli, as opposed to the ‘gliding’ gait planarians usually adopt in normal conditions.MethodsIn this study, we adapted commonly used nociceptive tests to further explore nociception in planarians of the species <jats:italic>Girardia dorotocephala</jats:italic>. By using behavioral analysis in open fields and place preferences, we managed to set up chemical, thermal and mechanical nociceptive tests. We also adapted RNA interference protocols and explored the effects of knocking down TRPA1 ion channels, one of the main effectors of chemically and thermally-induced nociceptive responses in vertebrates.ResultsConsequently, we demonstrated the reliability of the scrunching gait in this planarian species, which they displayed in a dose-dependent manner when exposed to the irritant AITC. We also showed that suppressing the expression of TRPA1 ion channels completely suppressed the scrunching gait, demonstrating the involvement of TRPA1 nociceptors in this nociceptive reaction. Besides, we also explored the effects of two common analgesics that both displayed strong antinociceptive properties. First, morphine reduced the chemically-induced nociceptive scrunching gaits by more than 20% and shifted the <jats:inline-formula><mml:math xmlns:mml=\\\"http://www.w3.org/1998/Math/MathML\\\"><mml:mi>E</mml:mi><mml:msub><mml:mi>C</mml:mi><mml:mn>50</mml:mn></mml:msub></mml:math></jats:inline-formula> of the dose–response curve by approximately 10 μM. Secondly, the NSAID meloxicam drastically reduced chemically-induced scrunching by up to 60% and reduced heat avoidance in place preference tests.DiscussionThus, we managed to characterize both behavioral and pharmacological aspects of <jats:italic>G. dorotocephala</jats:italic>’s nociception, further developing the use of planarians as a replacement model in pain studies and more globally the study of invertebrate nociception.\",\"PeriodicalId\":12630,\"journal\":{\"name\":\"Frontiers in Molecular Neuroscience\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Molecular Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fnmol.2024.1368009\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Molecular Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fnmol.2024.1368009","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Behavioral and pharmacological characterization of planarian nociception
IntroductionPain mostly arises because specialized cells called nociceptors detect harmful or potentially harmful stimuli. In lower animals with less convoluted nervous system, these responses are believed to be purely nociceptive. Amongst invertebrate animal models, planarians are becoming popular in a wide range of pharmacological and behavioral studies beyond the field of regeneration. Recent publications led the way on pain studies by focusing on nociceptive behaviors such as the ‘scrunching’ gait displayed under various noxious stimuli, as opposed to the ‘gliding’ gait planarians usually adopt in normal conditions.MethodsIn this study, we adapted commonly used nociceptive tests to further explore nociception in planarians of the species Girardia dorotocephala. By using behavioral analysis in open fields and place preferences, we managed to set up chemical, thermal and mechanical nociceptive tests. We also adapted RNA interference protocols and explored the effects of knocking down TRPA1 ion channels, one of the main effectors of chemically and thermally-induced nociceptive responses in vertebrates.ResultsConsequently, we demonstrated the reliability of the scrunching gait in this planarian species, which they displayed in a dose-dependent manner when exposed to the irritant AITC. We also showed that suppressing the expression of TRPA1 ion channels completely suppressed the scrunching gait, demonstrating the involvement of TRPA1 nociceptors in this nociceptive reaction. Besides, we also explored the effects of two common analgesics that both displayed strong antinociceptive properties. First, morphine reduced the chemically-induced nociceptive scrunching gaits by more than 20% and shifted the EC50 of the dose–response curve by approximately 10 μM. Secondly, the NSAID meloxicam drastically reduced chemically-induced scrunching by up to 60% and reduced heat avoidance in place preference tests.DiscussionThus, we managed to characterize both behavioral and pharmacological aspects of G. dorotocephala’s nociception, further developing the use of planarians as a replacement model in pain studies and more globally the study of invertebrate nociception.
期刊介绍:
Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.