Evolution of nociception and pain: evidence from fish models

Abstract

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'.

Keywords: analgesia; animal behaviour; fishes; invertebrates; nociceptors; zebrafish.

Figure 1.

(a) The mean (+s.d.) proportion of time spent within 5 cm of the object for control rainbow trout or those injected subcutaneously with acetic acid in each of the three test groups: 1. Exposure to a novel object; 2. Exposure to a familiar object or 3. Exposure to a novel object with morphine administered as an analgesic. **p < 0.001; *p < 0.05; n.s., not significant. (Reproduced from [26] with kind permission from Elsevier.) (b) Median percentage (±IQR, interquartile range) change from the pre-stimulation (baseline) values in the time spent active shown by 5 dpf zebrafish exposed to 0.1% acetic acid with 30 min prior exposure to different analgesic substances. CD, control disturbed with addition of water; CU, control undisturbed, with no addition of water; AC, acetic acid; AS, aspirin; MO, morphine; LI, lidocaine; FL, flunixin. ^‡Significant difference from the undisturbed control group; *significant difference from the disturbed control group (Mann–Whitney U-test with Bonferroni correction applied, p < 0.0026). Samples sizes: CD, n = 437; CU, n = 429; 0.1% AC, n = 416; 1 mg l⁻¹ AS, n = 416; 2.5 mg l⁻¹ AS, n = 438; 1 mg l⁻¹ MO, n = 435; 48 mg l⁻¹ MO, n = 439; 1 mg l⁻¹ LI, n = 402; 5 mg l⁻¹ LI, n = 391; 8 mg l⁻¹ FL, n = 411; and 20 mg l⁻¹ FL, n = 443. (Reproduced from [59] with kind permission from the Company of Biologists).

Figure 2.

Fractal dimension analysis of the complex swimming trajectories of adult zebrafish in control undisturbed zebrafish, in zebrafish anaesthetized but given no treatment, and in zebrafish given a fin clip, fin clip with pain-relief (PIT tag inserted in the abdomen), or subcutaneous injection of 1, 5 or 10% acetic acid yield values ranging from normal (1.15) to low (0.83), demonstrating a reduction in complexity in response to stressful or painful treatment, with arbitrary points indicating the impact of stress and mild, moderate (mod.) and severe pain. (Reproduced from [58] under Creative Commons Attribution License CC BY 4.0.)