BOX 1-4Which Responses Indicate Pain and Which Nonhuman Vertebrates Display Them?

To determine whether animals can experience pain (not simply nociception), it is necessary to show that they can discriminate painful from nonpainful states; make decisions based on this discrimination in a way that cannot arise from evolved nonconscious nociceptive responses (cf. text and Box 1-3); demonstrate motivations to avoid pain; and display affective states of fear or anxiety if threatened with noxious stimuli. In addition, animals experiencing pain might be expected to exhibit spontaneous behavioral changes including sustained signals of distress and impairments in normal behaviors such as sleep (see text and Box 1-3).

The discrimination of painful states: evidence from operant experiments. In some learning paradigms, drug infusions are used as “discriminative stimuli,” that is, experimental cues that predict which of two alternative learned operant responses will yield reward (e.g., whether a right or a left lever press will deliver food). In such experiments, rats show by shifting their operant response for food that they are able to distinguish injections of aspirin from injections of saline; furthermore, rats with arthritis learn this distinction more readily than do control rats (Weissman 1976; see also Colpaert 1978 and Swedberg et al. 1988). Thus, pain can serve as a discriminative stimulus, something the committee does not believe could occur without awareness.

Motivations to avoid pain or noxious stimuli. In learning paradigms in which an operant delivers an analgesic, rats in models-of-pain experiments lever press to self-medicate, and at a much higher rate than control animals. For example, rats with ligated spinal nerves lever press for clonidine, while controls do not (Martin et al. 2006). Rats, mice, primates, and pigeons also lever press to avoid electric shock (which may be painful depending on its intensity and duration; cf. Carlsson et al. 2006). Furthermore, oral self-administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is observed in lame (i.e., arthritic) rats and chickens but not in their healthy counterparts (Colpaert et al. 1980; Danbury et al. 2000).

Similar research has not been conducted on reptiles, amphibians, or fish but frogs, tadpoles, and fish do show conditioned active avoidance responses when a cue is paired with shock (Dunlop et al. 2003; Overmier and Papini 1986; Strickler-Shaw and Taylor 1991). Fish display this response even if it involves swimming over a hurdle that offers resistance (Behrend and Bitterman 1962). Similarly, fish learn to avoid hooks in angling trials (Beukema 1970). However, it is not certain that such simple avoidance learning requires the experience of conscious pain (see text and Box 1-3).

Spontaneous behavioral changes. Noxious stimuli can cause vocalization (including ultrasonic calls in rodents) and signs of apparent apathy in mammals (see Chapter 3). Moreover, the use of inescapable electric shock to create mammal models of depression is well documented in the neuroscience literature. Sleep disruption (assessed via EEG activity) occurs in rats with arthritis or persistent neuropathic pain (Blackburn-Munro 2004). Although these responses seem inconsistent with mere nociception (see Box 1-3), it is not yet proven that they result from pain. For instance, while fish injected with acid or bee venom show suppressed feeding and other behavioral alterations (Ashley et al. 2009; Sneddon et al. 2003a,b), such changes are not universally accepted as indicative of pain (Rose 2002). Recent studies with fish have shown, however, that the brain is active during noxious stimulation (with the forebrain being the most significantly affected) and that this activity differs from that of nonnoxious stimuli (Dunlop and Laming 2005; Nordgreen et al. 2007; Reilly et al. 2008).

In summary, evidence for the conscious experience of pain is strong for mammals and birds, but conclusive studies are either in progress for other taxa such as fish or have not yet been conducted. Pending such needed research, this report treats all vertebrates as capable of experiencing pain (see text).a

a

It is important to remember that there is scientific evidence to suggest that pain or the threat of noxious stimuli causes fear and/or anxiety. Much research shows that the mere threat of foot shock (i.e., the application of electric current on the foot) induces behavioral and physiological signs of stress in rats and mice that can be alleviated with compounds that reduce anxiety in humans (anxiolytics). Similar data are available for pigeons (Vanover et al. 2004). Furthermore, in one experiment an anxiety-inducing drug was used as a “discriminative stimulus” in pigs: the operant that would yield food was varied experimentally (e.g., from right lever to left lever) according to whether the subject was simultaneously infused with the anxiogenic drug or saline. Animals learned this discrimination successfully and performed a different operant for food depending on the compound of their infusion. The pigs were subsequently exposed to electric shock, which caused them to spontaneously select the anxiogenic rather than the saline operant when working for food. This finding suggests that the pigs’ experience of the electric shock included the sensation of anxiety (Carey and Fry 1993). No such research has been conducted on reptiles, amphibians, or fish.

It is important to remember that there is scientific evidence to suggest that pain or the threat of noxious stimuli causes fear and/or anxiety. Much research shows that the mere threat of foot shock (i.e., the application of electric current on the foot) induces behavioral and physiological signs of stress in rats and mice that can be alleviated with compounds that reduce anxiety in humans (anxiolytics). Similar data are available for pigeons (Vanover et al. 2004). Furthermore, in one experiment an anxiety-inducing drug was used as a “discriminative stimulus” in pigs: the operant that would yield food was varied experimentally (e.g., from right lever to left lever) according to whether the subject was simultaneously infused with the anxiogenic drug or saline. Animals learned this discrimination successfully and performed a different operant for food depending on the compound of their infusion. The pigs were subsequently exposed to electric shock, which caused them to spontaneously select the anxiogenic rather than the saline operant when working for food. This finding suggests that the pigs’ experience of the electric shock included the sensation of anxiety (Carey and Fry 1993). No such research has been conducted on reptiles, amphibians, or fish.

From: 1, Pain in Research Animals: General Principles and Considerations

Cover of Recognition and Alleviation of Pain in Laboratory Animals
Recognition and Alleviation of Pain in Laboratory Animals.
National Research Council (US) Committee on Recognition and Alleviation of Pain in Laboratory Animals.
Washington (DC): National Academies Press (US); 2009.
Copyright © 2009, National Academy of Sciences.

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