CAB Reviews 2018 13, No. 049 Pain sensitivity in fish Paul Schroeder Address: Department for Biomedical Services, Oxford University, The Old Observatory, South Parks Rd, Oxford, OX1 3RQ, UK. Correspondence: Paul Schroeder. Email: [email protected] Received: 9 August 2018 Accepted: 16 October 2018 doi: 10.1079/PAVSNNR201813049 The electronic version of this article is the definitive one. It is located here: http://www.cabi.org/cabreviews © CAB International 2018 (Online ISSN 1749-8848) Abstract The question of whether fish have the capacity to experience a state akin to pain was first empirically addressed by Jan Verheijen’s seminal study on carps in 1983. Subsequently, comprehensive evidence has been presented not only on the anatomical prerequisites for a pain system in several fish species, but also for a behavioural component. Opinions against fish perceiving pain focus on the difference in neuroanatomy between higher mammals and lower vertebrates that do not possess a neocortex. Finally, the successful (behaviour sparing) use of analgesics can be interpreted as further evidence that fish are able to perceive pain and can be adversely affected by a painful event. Keywords: Fish, Pain, Sentience, Analgesia Review Methodology: The author searched the following databases, on or before 6th of August 2018: PubMed and Web of Science. Search terms included ‘fish & sentience’, ‘fish & pain’, ‘fish & pain & sensitivity’ and ‘fish & analgesia’. For the more general (introductory) section, the additional terms ‘pain & pathways’ and ‘animal & pain’ were also used. Introduction There are a range of pain categories according to location (deep, visceral, cutaneous) and duration (acute, Pain in humans has been defined as the unpleasant sensory chronic), with many possibilities for further gradation or emotional experience associated with actual or potential with respect to intensity and causation [4]. Pain is of tissue damage [1]. This human-centred concept has primary concern when assessing if an animal study con- been expanded for animals that may not experience stitutes a regulated scientific procedure with the potential the same sensation to also incorporate the triggering to precipitate pain, suffering, distress and lasting harm of protective motor actions, learned avoidance [2] and [5]. Animals cannot verbalize their pain so that in order a degree of awareness of damage or threat [3]. Bateson [4] to detect it the researcher has to rely on his or her expanded this concept further, identifying eight points interpretation of their behaviour [6] and physiology [7]. indicative of the presence of pain in an animal: (1) poss- The lack of reliable assessment of pain in animals has ession of functional receptors sensitive to noxious stimuli, been associated with variable pain relief in veterinary (2) possession of a structure analogous to the human medicine [7, 8]. cerebral cortex, (3) possession of a nervous pathways Fish constitute more than half of all species of extant connecting nociceptive receptors to higher brain struc- vertebrates [9]. The question of whether fish possesses the tures, (4) possession of receptors for opioid substances capacity for sentience remained largely unexplored until found in the central nervous system, (5) analgesics modify the 1980s, when Verheijen’s (1983) studies on carp showed the animal’s response to noxious stimuli and are chosen that these animals experienced similar sensations to pain by the animal when the experience is unavoidable, and fear when hooked and captured [10, 11]. Since then (6) animals respond to noxious stimuli by avoiding them there has been an increasing number of publications or minimizing damage to the body, (7) this avoidance focusing on endorsing the concept that fish have the behaviour is inelastic and (8) response to noxious stimuli capacity to suffer [12], including the ability to experience persists and the animal learns how to associate neutral pain beyond pure reflexes both in the context of sports events with noxious stimuli. fishing [13] and experimentally generated pain [14]. http://www.cabi.org/cabreviews 2 CAB Reviews Receptors and Fibres nociceptive events could change the motivational state of trout, which resumed feeding later after injection with bee Pain has been described as a result of the stimulation of the venom or acetic acid, compared with the group injected nociceptive system, a sensory system integral in an animal’s with saline. Braithwaite and Boulcoutt [25] argue that these control for preserving homoeostasis, beyond pure reflex three levels of analysis (anatomical, electrophysiological and responses [15]. Nociception is the detection of potentially behavioural) represent compelling evidence that teleosts injurious stimuli [16] that stimulate nociceptors, receptors possess nociceptors and that their behaviour is affected by that preferentially detect damage. These primary sensory algesic stimuli. neurons are activated by stimuli signalling real or potential Opinions against fish perceiving pain focus on the differ- tissue damage [17] with their free nerve endings dispersed ence in neuroanatomy between humans and non-primate all over the body whilst their cell bodies are located in vertebrates such as fish that do not possess a neocortex the trigeminal (head) or dorsal root ganglia (spinal). There and have smaller brains with fewer neurons. Rose [26] are three main types of nociceptor fibre type: free nerve suggests that the ‘conscious experience of fear and pain is a endings associated with myelinated A-β fibres mostly neurological impossibility’. Other authors argue that if detect innocuous stimuli in skin, muscle or joints though an analgesic improves the situation, this is proof that pain some contribute to pain; the more thinly myelinated A-δ was experienced [27], which supports the findings in the fibres (mostly linked to intense mechanical stimuli) and study [14] showing that morphine significantly reduced thirdly the slower conducting unmyelinated C-fibres (linked pain-related behaviours. Apart from the behavioural to heat and chemical stimuli) are mainly associated with studies mentioned above, pain perception in fish has been detection of noxious stimuli [18]. Five percent of all endorsed through the identification of opioid receptors in C-nociceptors fire to mechanical stimuli only [19] and the animals’ nervous tissue [27, 28]. some can also register itch and innocuous temperatures [17]. Nociceptors have been identified in mammals, birds, reptiles and teleosts but not in the older chordate clades Reponses to Pain in Fish of elasmobranchs or hagfish. In lampreys receptors sen- sitive to noxious stimuli were identified, though respon- Pain perception in fish is likely to differ from human experi- siveness was only intermittent [20]. Despite the lack ence and may not be consistent with our understanding of conclusive evidence for nociceptors in chordate taxa of mammalian physiology [29, 30]. Rather than ruling predating teleosts, unmyelinated structures resembling out pain on the basis of mere anatomical differences, C-fibres were found in hagfish and myelinated A-δ fibres judgements should be made based on evidence. For were found in elasmobranchs. example, as a starting point, the understanding of pain in While both A-δ and C-fibres are found in higher a particular group of animals can be based upon behavioural vertebrates and teleost fish; the latter constitute 60% or physiological changes linked to painful events in other of fibres in mouse skin [21] and also the majority of fibre species, such as post-surgically increased respiratory rates type found in other mammals, birds and amphibians in cats and dogs and a higher opercular beat rate for fish [19, 22] but only 4% of the fibre type found in teleosts [16]. subjected to trauma [29]. Several studies attempt to link behavioural and physio- logical responses: Fin-clipped Nile tilapia (Oreochromis Evidence for Pain in Fish niloticus) showed that there was an increase in time spent in the illuminated section of the tank accompanied by Of Bateson’s criteria for defining pain in animals (1991) an increase in swimming activity. A further observation suggesting that a number of factors exceeding nociception interpreted as pain response was the emptying of mucus would need to be in place to constitute an emotional state cells in the gills, usually associated with stressful events [31] whereby suffering or discomfort is experienced, several and recorded 1 h after the fin clip. The same study also have been identified in fish: the reaction to a noxious found a significant increase in plasma cortisol yet there was stimulus by avoidance or damage minimization was shown no information on time elapsed post-surgery. The study for pike as early as 1970 [23]. The inelastic avoidance was not able to discriminate between the stress imposed response and learned pain association were shown for by the clip and that by handling stress. goldfish and trout [24]. A study focusing on thermonociception in goldfish Exploring both the anatomical and behavioural com- (Carassius auratus) reported an escape response modulated ponents of a pain system in fish, Sneddon [14] found by administration of morphine, when an attached thermal three nociceptor types (polymodal, mechanochemical and device became too hot [32]. Investigations of post- mechanothermal) on the head of rainbow trout. The same nociceptive behaviours in rainbow trout (Oncorhynchus study also confirmed the presence of A-δ and C-fibres in mykiss)