Evolution of nociception and pain: evidence from fish models

In order to survive, animals must avoid injury and be able to detect potentially damaging stimuli via nociceptive mechanisms. If the injury is accompanied by a negative affective component, future behaviour should be altered and one can conclude the animal experienced the discomfort associated with pain. Fishes are the most successful vertebrate group when considering the number of species that have filled a variety of aquatic niches. The empirical evidence for nociception in fishes from the underlying molecular biology, neurobiology and anatomy of nociceptors through to whole animal behavioural responses is reviewed to demonstrate the evolutionary conservation of nociception and pain from invertebrates to vertebrates. Studies in fish have shown that the biology of the nociceptive system is strikingly similar to that found in mammals. Further, potentially painful events result in behavioural and physiological changes such as reduced activity, guarding behaviour, suspension of normal behaviour, increased ventilation rate and abnormal behaviours which are all prevented by the use of pain-relieving drugs. Fish also perform competing tasks less well when treated with a putative painful stimulus. Therefore, there is ample evidence to demonstrate that it is highly likely that fish experience pain and that pain-related behavioural changes are conserved across vertebrates. This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.

[1]  L. Sneddon,et al.  Ethical considerations in fish research. , 2019, Journal of fish biology.

[2]  C. Baird,et al.  The pilot study. , 2000, Orthopedic nursing.

[3]  P. Sandroni,et al.  International association for the study of pain , 1986, Pain.

[4]  C. Mccrohan,et al.  The efficacy of three types of analgesic drugs in reducing pain in the rainbow trout, Oncorhynchus mykiss , 2011 .

[5]  F. Prato,et al.  Pulsed Magnetic Field Induced “Analgesia” in the Land Snail, Cepaea nemoralis, and the Effects of μ, δ, and κ Opioid Receptor Agonists/Antagonists , 1997, Peptides.

[6]  B. Burrell Comparative biology of pain: What invertebrates can tell us about how nociception works. , 2017, Journal of neurophysiology.

[7]  A. Campos,et al.  The orofacial antinociceptive effect of Kaempferol-3-O-rutinoside, isolated from the plant Ouratea fieldingiana, on adult zebrafish (Danio rerio). , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[8]  M. Leach,et al.  Development of a Piglet Grimace Scale to Evaluate Piglet Pain Using Facial Expressions Following Castration and Tail Docking: A Pilot Study , 2017, Front. Vet. Sci..

[9]  M. Minero,et al.  Development of the Horse Grimace Scale (HGS) as a Pain Assessment Tool in Horses Undergoing Routine Castration , 2014, PloS one.

[10]  J. J. Chen,et al.  Regulation of opioid receptors in rat sensory neurons in culture. , 1997, Molecular pharmacology.

[11]  C. Mccrohan,et al.  Effect of noxious stimulation upon antipredator responses and dominance status in rainbow trout , 2009, Animal Behaviour.

[12]  A. Waterman-Pearson,et al.  Quantification of the pain and distress responses to castration in young lambs. , 1999, Research in veterinary science.

[13]  M. Purnell,et al.  The Evolutionary Emergence of Vertebrates From Among Their Spineless Relatives , 2009, Evolution: Education and Outreach.

[14]  P. Musienko,et al.  Zebrafish models relevant to studying central opioid and endocannabinoid systems , 2018, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[15]  G. G. Neely,et al.  Conserved systems and functional genomic assessment of nociception , 2013, The FEBS journal.

[16]  Lynne U. Sneddon,et al.  Pain in aquatic animals , 2015, The Journal of Experimental Biology.

[17]  A. Kuhad,et al.  TRP channels: potential drug target for neuropathic pain , 2016, Inflammopharmacology.

[18]  A. Monteiro-Moreira,et al.  Antinociceptive activity of ethanolic extract of Azadirachta indica A. Juss (Neem, Meliaceae) fruit through opioid, glutamatergic and acid-sensitive ion pathways in adult zebrafish (Danio rerio). , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[19]  L. Sneddon Comparative Physiology of Nociception and Pain. , 2018, Physiology.

[20]  H O Handwerker,et al.  Responsiveness and functional attributes of electrically localized terminals of cutaneous C-fibers in vivo and in vitro. , 1992, Journal of neurophysiology.

[21]  U. Baumgärtner,et al.  Quick Discrimination of Adelta and C Fiber Mediated Pain Based on Three Verbal Descriptors , 2010, PloS one.

[22]  Q. Al-Jubouri,et al.  Impact of analgesic drugs on the behavioural responses of larval zebrafish to potentially noxious temperatures , 2017 .

[23]  S. Azad,et al.  Pharmacology of peripheral opioid receptors , 2011, Current opinion in anaesthesiology.

[24]  M. Gerstein,et al.  Proton sensitivity of ASIC1 appeared with the rise of fishes by changes of residues in the region that follows TM1 in the ectodomain of the channel , 2005, The Journal of physiology.

[25]  A. A. Romanovsky,et al.  CALL FOR PAPERS Physiology and Pharmacology of Temperature Regulation Thermoregulation: some concepts have changed. Functional architecture of the thermoregulatory system , 2007 .

[26]  Steven P Wilson,et al.  Selective Inflammatory Pain Insensitivity in the African Naked Mole-Rat (Heterocephalus glaber) , 2008, PLoS biology.

[27]  D. Julius,et al.  The capsaicin receptor: a heat-activated ion channel in the pain pathway , 1997, Nature.

[28]  E. Smith,et al.  Nociceptors: a phylogenetic view , 2009, Journal of Comparative Physiology A.

[29]  M. Gentle,et al.  Animal Studies Repository Animal Studies Repository Novel Object Test: Examining Nociception and Fear in the Rainbow Trout , 2022 .

[30]  C. M. Leung Neuropsychopharmacology: The Fifth Generation of Progress , 2003 .

[31]  L. U. Sneddon,et al.  Do fishes have nociceptors? Evidence for the evolution of a vertebrate sensory system , 2003, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[32]  J. C. Taylor,et al.  A novel zebrafish-based model of nociception , 2017, Physiology & Behavior.

[33]  E. Smith,et al.  ASICs and mammalian mechanoreceptor function , 2015, Neuropharmacology.

[34]  R. Shingai,et al.  Evolution of thermoTRP ion channel homologs in vertebrates. , 2006, Physiological genomics.

[35]  D. Raible,et al.  Modeling Nociception in Zebrafish: A Way Forward for Unbiased Analgesic Discovery , 2015, PloS one.

[36]  A. Waterman-Pearson,et al.  Comparison of pethidine, buprenorphine and ketoprofen for postoperative analgesia after ovariohysterectomy in the cat , 1998, Veterinary Record.

[37]  P. Snow,et al.  Localization of enkephalin immunoreactivity in the spinal cord of the long‐tailed ray Himantura fai , 1996, The Journal of comparative neurology.

[38]  G. Stefano,et al.  Invertebrate proenkephalin: δ opioid binding sites in leech ganglia and immunocytes , 1997, Brain Research.

[39]  K. Craig,et al.  Coding of facial expressions of pain in the laboratory mouse , 2010, Nature Methods.

[40]  D. Sprecher,et al.  A lameness scoring system that uses posture and gait to predict dairy cattle reproductive performance. , 1997, Theriogenology.

[41]  C. Stucky,et al.  Receptive properties of mouse sensory neurons innervating hairy skin. , 1997, Journal of neurophysiology.

[42]  A I Basbaum,et al.  Impaired nociception and pain sensation in mice lacking the capsaicin receptor. , 2000, Science.

[43]  Shivayogi M Hugar,et al.  An In Vivo Study , 2015 .

[44]  M. P. Wilkie,et al.  Morphine uptake, disposition, and analgesic efficacy in the common goldfish (Carassius auratus) , 2009 .

[45]  Q. Al-Jubouri,et al.  Reduction in activity by noxious chemical stimulation is ameliorated by immersion in analgesic drugs in zebrafish , 2017, Journal of Experimental Biology.

[46]  P. Pasricha Unraveling the mystery of pain in chronic pancreatitis , 2012, Nature Reviews Gastroenterology &Hepatology.

[47]  J. Vega,et al.  Acid-sensing ion channels (ASICs) 2 and 4.2 are expressed in the retina of the adult zebrafish , 2015, Cell and Tissue Research.

[48]  P. Mantyh The neurobiology of skeletal pain , 2014, The European journal of neuroscience.

[49]  Amy L. Miller,et al.  The Assessment of Post-Vasectomy Pain in Mice Using Behaviour and the Mouse Grimace Scale , 2012, PloS one.

[50]  R. Dores,et al.  Evolution of the opioid/ORL‐1 receptor gene family , 2010, Annals of the New York Academy of Sciences.

[51]  J. Roughan,et al.  Behavioural effects of ovariohysterectomy and oral administration of meloxicam in laboratory housed rabbits. , 2009, Research in veterinary science.

[52]  P. Laming,et al.  Trade-offs between feeding and shock avoidance in goldfish (Carassius auratus) , 2008 .

[53]  Makoto Tominaga,et al.  Drosophila Painless Is a Ca2+-Requiring Channel Activated by Noxious Heat , 2008, The Journal of Neuroscience.

[54]  Andrew R. Cossins,et al.  Behavioural analysis of a nociceptive event in fish: Comparisons between three species demonstrate specific responses , 2008 .

[55]  J. Roughan,et al.  Behavioural effects of laparotomy and analgesic effects of ketoprofen and carprofen in rats , 2001, Pain.

[56]  C. Mccrohan,et al.  Properties of corneal receptors in a teleost fish , 2006, Neuroscience Letters.

[57]  Lynne U. Sneddon,et al.  Anatomical and electrophysiological analysis of the trigeminal nerve in a teleost fish, Oncorhynchus mykiss , 2002, Neuroscience Letters.

[58]  R. Elwood,et al.  Trade-offs between predator avoidance and electric shock avoidance in hermit crabs demonstrate a non-reflexive response to noxious stimuli consistent with prediction of pain , 2016, Behavioural Processes.

[59]  S. Ferreira,et al.  II - Prostaglandin hyperalgesia: the peripheral analgesic activity of morphine, enkephalins and opioid antagonists. , 1979, Prostaglandins.

[60]  T. Park,et al.  A plethora of painful molecules , 2004, Current Opinion in Neurobiology.

[61]  T. Shippenberg,et al.  Peripheral opioid receptors mediating antinociception in inflammation. Evidence for involvement of mu, delta and kappa receptors. , 1989, The Journal of pharmacology and experimental therapeutics.

[62]  C. Belmonte,et al.  Responses of cat corneal sensory receptors to mechanical and thermal stimulation. , 1981, The Journal of physiology.

[63]  M. Leider Goodman & Gilman's The Pharmacological Basis of Therapeutics , 1985 .

[64]  Lynne U. Sneddon,et al.  Trigeminal somatosensory innervation of the head of a teleost fish with particular reference to nociception , 2003, Brain Research.

[65]  H. Akil,et al.  3 OPIOID PEPTIDES AND THEIR RECEPTORS : OVERVIEW AND FUNCTION IN PAIN MODULATION , 2001 .

[66]  J. R. Sneyd,et al.  Opioid analgesics , 2017, Reactions Weekly.

[67]  E. Walters Nociceptive Biology of Molluscs and Arthropods: Evolutionary Clues About Functions and Mechanisms Potentially Related to Pain , 2018, Front. Physiol..

[68]  P A Flecknell,et al.  Effects of surgery and analgesic administration on spontaneous behaviour in singly housed rats. , 2000, Research in veterinary science.

[69]  Lynne U. Sneddon,et al.  The Evidence for Pain in Fish: The Use of Morphine as an Analgesic , 2003 .

[70]  G. Teskey,et al.  A functional role for an opiate system in snail thermal behavior. , 1983, Science.

[71]  R. Peterson,et al.  Development of an opioid self-administration assay to study drug seeking in zebrafish , 2017, Behavioural Brain Research.

[72]  C. Stein,et al.  Painful inflammation-induced increase in mu-opioid receptor binding and G-protein coupling in primary afferent neurons. , 2003, Molecular pharmacology.

[73]  G. Flik,et al.  Tailfin clipping, a painful procedure: Studies on Nile tilapia and common carp , 2010, Physiology & Behavior.

[74]  A. Kalueff,et al.  Understanding nociception-related phenotypes in adult zebrafish: Behavioral and pharmacological characterization using a new acetic acid model , 2019, Behavioural Brain Research.

[75]  S. Terashima,et al.  C mechanical nociceptive neurons in the crotaline trigeminal ganglia , 1994, Neuroscience Letters.

[76]  S. Adamo,et al.  Defining and assessing animal pain , 2014, Animal Behaviour.

[77]  H. Koerber,et al.  Glial Cell Line-Derived Neurotrophic Factor Expression in Skin Alters the Mechanical Sensitivity of Cutaneous Nociceptors , 2006, The Journal of Neuroscience.

[78]  J. Kehne,et al.  Inflammation-Induced Reduction of Spontaneous Activity by Adjuvant: A Novel Model to Study the Effect of Analgesics in Rats , 2007, Journal of Pharmacology and Experimental Therapeutics.

[79]  J. Maloteaux,et al.  Interleukin-1β induces long-term increase of axonally transported opiate receptors and substance P , 1995, Neuroscience.

[80]  P. Sherman,et al.  4. The Population Structure of Naked Mole-Rat Colonies , 2017 .

[81]  Iain S. Young,et al.  Welfare Challenges Influence the Complexity of Movement: Fractal Analysis of Behaviour in Zebrafish , 2019, Fishes.

[82]  E. Walters,et al.  Nociceptive Sensitization Reduces Predation Risk , 2014, Current Biology.

[83]  Ample evidence for fish sentience and pain , 2018 .

[84]  C. Mccrohan,et al.  Nociception in fish: stimulus–response properties of receptors on the head of trout Oncorhynchus mykiss , 2007, Brain Research.

[85]  C. Mccrohan,et al.  Characterisation of chemosensory trigeminal receptors in the rainbow trout, Oncorhynchus mykiss: responses to chemical irritants and carbon dioxide , 2012, Journal of Experimental Biology.

[86]  Gary R Lewin,et al.  Mechanosensation and pain. , 2004, Journal of neurobiology.

[87]  R. Dores,et al.  Analyzing the evolution of the opioid/orphanin gene family. , 2002, Mass spectrometry reviews.

[88]  D. Cain,et al.  Response properties of mechanoreceptors and nociceptors in mouse glabrous skin: an in vivo study. , 2001, Journal of neurophysiology.

[89]  G. Matthews,et al.  Trigeminal sensory neurons of the sea lamprey , 1978, Journal of comparative physiology.

[90]  Q. Al-Jubouri,et al.  Behavioural responses of fish larvae modulated by analgesic drugs after a stress exposure , 2017 .

[91]  Lynne U. Sneddon,et al.  Evolution of nociception in vertebrates: comparative analysis of lower vertebrates , 2004, Brain Research Reviews.

[92]  T. Lynagh,et al.  Acid-sensing ion channels emerged over 600 Mya and are conserved throughout the deuterostomes , 2018, Proceedings of the National Academy of Sciences.

[93]  W. Muir,et al.  Thermonociception in fish: Effects of two different doses of morphine on thermal threshold and post-test behaviour in goldfish (Carassius auratus) , 2009 .

[94]  Loren J. Martin,et al.  The Rat Grimace Scale: A partially automated method for quantifying pain in the laboratory rat via facial expressions , 2011, Molecular pain.

[95]  A. Campos,et al.  Adult Zebrafish (Danio rerio) As a Model for the Study of Corneal Antinociceptive Compounds. , 2018, Zebrafish.