Acute and chronic stress prevents responses to pain in zebrafish: evidence for stress-induced analgesia

Abstract

The state of an animal prior to the application of a noxious stimulus can have a profound effect on their nociceptive threshold and subsequent behaviour. In mammals, the presence of acute stress preceding a painful event can have an analgesic effect whereas the presence of chronic stress can result in hyperalgesia. While considerable research has been conducted on the ability of stress to modulate mammalian responses to pain, relatively little is known about fish. This is of particular concern given that zebrafish (Danio rerio) are an extensively used model organism subject to a wide array of invasive procedures where the level of stress prior to experimentation could pose a major confounding factor. This study, therefore, investigated the impact of both acute and chronic stress on the behaviour of zebrafish subjected to a potentially painful laboratory procedure, the fin clip. In stress-free individuals, those subjected to the fin clip spent more time in the bottom of the tank, had reduced swimming speeds and less complex swimming trajectories; however, these behavioural changes were absent in fin-clipped fish that were first subject to either chronic or acute stress, suggesting the possibility of stress-induced analgesia (SIA). To test this, the opioid antagonist naloxone was administered to fish prior to the application of both the stress and fin-clip procedure. After naloxone, acutely stressed fin-clipped zebrafish exhibited the same behaviours as stress-free fin-clipped fish. This indicates the presence of SIA and the importance of opioid signalling in this mechanism. As stress reduced nociceptive responses in zebrafish, this demonstrates the potential for an endogenous analgesic system akin to the mammalian system. Future studies should delineate the neurobiological basis of stress-induced analgesia in fish.

Acute and Chronic Effects of Fin Amputation on Behavior Performance of Adult Zebrafish in 3D Locomotion Test Assessed with Fractal Dimension and Entropy Analyses and Their Relationship to Fin Regeneration

“…Previous publications emphasized that the behavioral changes after fin clipping as a response to a noxious event, fin damage, are not transient and last for up to 6 h after the procedure. However, these studies do not specifically test for long-term behavioral effects since the cortisol level returned to baseline levels before 24 h post-stressor [31,48,50].…”

“…Several previous studies had demonstrated that the behavioral changes after the finamputation procedure are related to the pain elicited from the amputation process. Therefore, it is intriguing to observe the long-term effect and effectiveness of a commonly used drug with pain-relieving properties, lidocaine, in preventing any behavioral responses to the fin amputation during the whole recovery time (10 days) [30,31,45,49,66]. This study…”

“…In zebrafish, FD reduces the 3D complex swimming trajectories of zebrafish to one value and was used in a previous study to quantify their swimming behavior provoked by the presence of hypochlorite in the water by using FD analysis [ 26 ]. It has also been applied to various painful treatments in zebrafish to produce an arbitrary pain intensity scale [ 30 , 31 ]. However, even though FD is used for behavioral monitoring, it mainly presents the overall trend of behavioral changes that are limited in presenting global and local information of movement changes after exposure to stimuli.…”

Effects of parasites and predators on nociception: decreases analgesia reduces overwinter survival in root voles (Rodentia: Cricetidae)

“…Although various reports have highlighted the positive role of analgesia induced by stress in animal defense responses (Amit and Galina 1986, Butler and Finn 2009, Thomson et al 2020, the causal correlation between nociception and survival at the population level is obscure. Our study is the first to exami ne whether nociceptive responses affect the overwinter survival of small mammal populations.…”

Kinds of Harm: Animal Law Language from a Scientific Perspective

“…Of note, based on the studies on mammals, an exposure to acute stress can reduce pain due to stress-induced analgesia [12]. Recently, this phenomenon was also reported in zebrafish [13]. In contrast, chronic stress leading to distress has been the background for studies on so-called learned helplessness [14].…”