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It is widely accepted that animals often experience pain and distress as a result of their use in scientific experimentation. However, unlike human suffering, the wide range of acute, recur- rent, and chronic stressors and trauma on animals is rarely evaluated. In order to better understand the cumulative effects of captivity and laboratory research conditions on animals, we explore parallels between human experiences of pain and psy- chological distress and those of animals based on shared brain structures and physiological mechanisms. We review anatomical, physiological, and behavioral similarities between humans and other animals regarding the potential for suffering. In addition, we examine associations between research conditions and indica- tors of pain and distress. We include 4 case studies of common animal research protocols in order to illustrate incidental and experimental factors that can lead to animal suffering. Finally, we identify parallels between established traumatic conditions for humans and existing laboratory conditions for animals.
It is widely accepted that animals often experience pain and distress as a result of their use in scientific experimentation. However, unlike human suffering, the wide range of acute, recur- rent, and chronic stressors and trauma on animals is rarely evaluated. In order to better understand the cumulative effects of captivity and laboratory research conditions on animals, we explore parallels between human experiences of pain and psy- chological distress and those of animals based on shared brain structures and physiological mechanisms. We review anatomical, physiological, and behavioral similarities between humans and other animals regarding the potential for suffering. In addition, we examine associations between research conditions and indica- tors of pain and distress. We include 4 case studies of common animal research protocols in order to illustrate incidental and experimental factors that can lead to animal suffering. Finally, we identify parallels between established traumatic conditions for humans and existing laboratory conditions for animals.
It is widely accepted that animals often experience pain and distress as a result of their use in scientific experimentation. However, unlike human suffering, the wide range of acute, recur- rent, and chronic stressors and trauma on animals is rarely evaluated. In order to better understand the cumulative effects of captivity and laboratory research conditions on animals, we explore parallels between human experiences of pain and psy- chological distress and those of animals based on shared brain structures and physiological mechanisms. We review anatomical, physiological, and behavioral similarities between humans and other animals regarding the potential for suffering. In addition, we examine associations between research conditions and indica- tors of pain and distress. We include 4 case studies of common animal research protocols in order to illustrate incidental and experimental factors that can lead to animal suffering. Finally, we identify parallels between established traumatic conditions for humans and existing laboratory conditions for animals.
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Publisher: Routledge Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK Journal of Trauma & Dissociation Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/wjtd20 Parallels in Sources of Trauma, Pain, Distress, and Suffering in Humans and Nonhuman Animals Hope Ferdowsian MDMPH a & Debra Merskin PhD b a Physician's Committee for Responsible Medicine; Department of Medicine, George Washington University, Washington, DC, USA b School of Journalism & Communication, University of Oregon, Eugene, Oregon, USA Available online: 24 Jan 2012 To cite this article: Hope Ferdowsian MDMPH & Debra Merskin PhD (2012): Parallels in Sources of Trauma, Pain, Distress, and Suffering in Humans and Nonhuman Animals, Journal of Trauma & Dissociation, 13:4, 448-468 To link to this article: http://dx.doi.org/10.1080/15299732.2011.652346 PLEASE SCROLL DOWN FOR ARTICLE Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae, and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand, or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material. Journal of Trauma & Dissociation, 13:448468, 2012 Copyright Taylor & Francis Group, LLC ISSN: 1529-9732 print/1529-9740 online DOI: 10.1080/15299732.2011.652346 Parallels in Sources of Trauma, Pain, Distress, and Suffering in Humans and Nonhuman Animals HOPE FERDOWSIAN, MD, MPH Physicians Committee for Responsible Medicine; Department of Medicine, George Washington University, Washington, DC, USA DEBRA MERSKIN, PhD School of Journalism & Communication, University of Oregon, Eugene, Oregon, USA It is widely accepted that animals often experience pain and distress as a result of their use in scientic experimentation. However, unlike human suffering, the wide range of acute, recur- rent, and chronic stressors and trauma on animals is rarely evaluated. In order to better understand the cumulative effects of captivity and laboratory research conditions on animals, we explore parallels between human experiences of pain and psy- chological distress and those of animals based on shared brain structures and physiological mechanisms. We review anatomical, physiological, and behavioral similarities between humans and other animals regarding the potential for suffering. In addition, we examine associations between research conditions and indica- tors of pain and distress. We include 4 case studies of common animal research protocols in order to illustrate incidental and experimental factors that can lead to animal suffering. Finally, we identify parallels between established traumatic conditions for humans and existing laboratory conditions for animals. KEYWORDS distress, ethics, posttraumatic stress, stress It is widely acknowledged that nonhuman animals (hereafter, animals) often experience pain and distress in the course of their use in scien- tic experimentation (Gregory, 2004; Recognition, 2009). However, human Received 11 August 2011; accepted 20 October 2011. Address correspondence to Debra Merskin, PhD, School of Journalism & Communi- cation, University of Oregon, Eugene, OR 97403. E-mail: dmerskin@uoregon.edu 448 D o w n l o a d e d
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Journal of Trauma & Dissociation, 13:448468, 2012 449 interventions to minimize pain and distress in animals commonly focus on reducing the numbers of animals used and making changes to specic pro- tocols rather than evaluating the suffering individual animals experience over the course of their lifetimes. This differs from the consideration of human suffering, in which researchers examine the impact of acute, recur- rent, and chronic trauma on individuals. Because animals are frequently used in research, there is an ethical imperative to better understand the cumulative effects of captivity and the rigors of laboratory research on animals. In 1789, moral philosopher and legal scholar Jeremy Bentham noted that it is the ability to suffer, not the ability to reason, that should be the insuperable line (1789/1836, p. 236) that determines the treatment of other beings, including infants, adults with particular disabilities, and animals. According to Bentham, A full-grown horse or dog is beyond comparison a more rational, as well as a more conversable animal, than an infant of a day or a week or even a month, old. But suppose the case were otherwise, what would it avail? The question is not, Can they reason? Nor, Can they talk? But, can they suffer? (p. 236) Knowledge of pain, psychological distress, and suffering in humans and other animals has evolved signicantly since Benthams statement was rst published. Only in relatively recent history have scientists and physicians acknowledged that human infants experience pain (Bellieni & Buonocore, 2010; Chamberlain, 1989). Furthermore, some have suggested that babies and young children may experience more pain than adults because they have not yet developed a mechanism that may reduce pain severity (Dombrowski, 1997; Pluhar, 1993). As articulated by the International Association for the Study of Pain (2007), Pain is always subjective, and the inability to communicate verbally does not negate the possibility that an individual is experiencing pain (Merskey & Bogduk, 1994, p. 211). Although this statement was intended to apply to infants and other humans unable to articulate their experiences, it can also be applied to nonhuman animals. Suffering has been characterized in several ways. For example, DeGrazia (2002) has posited that suffering occurs when the source of pain is unknown, when the meaning of the pain is dire, or when the pain is appar- ently without end (p. 35). Suffering has been dened as an unpleasant subjective experience (Singer, 2006) or a state of severe distress associ- ated with events that threaten the intactness of the person (Cassell, 2004, p. 32). Although sometimes used synonymously with physical pain, suffer- ing can also originate and manifest psychologically. Perhaps more broadly, suffering has been described by Morton and Hau (2002, p. 459) as a nega- tive emotional state which derives from adverse physical, physiological, and psychological circumstances, in accordance with the cognitive capacity of D o w n l o a d e d
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450 H. Ferdowsian and D. Merskin the species and the individual being, and its lifes experience. Dawkins (2008) has suggested that animal suffering can be measured empirically through the evaluation of emotional states, as indicated by behavioral and physiological parameters. Suffering can be dened as a set of negative emo- tions such as fear and pain and recognized operationally as states caused by negative reinforcers (Dawkins, 2008). Thus, suffering can manifest as physical or mental experiences or both. Here we address the following questions, drawing on Bentham (1789/1836): In what ways do animals suffer physically and psychologically as a result of their use in laboratory research, and what are some of the gen- eral factors that can lead to their suffering? In order to address our central questions, we review anatomical, physiological, and behavioral similarities between humans and other animals as they relate to the capacity for pain, psychological distress, and suffering. We draw upon an evolutionary frame- work that acknowledges convergence and divergence across species (Brne, 2008; Cantor & Joyce, 2009; Marino, 2002; Stevens & Price, 2000). We also explore evidence regarding the association between laboratory research con- ditions, including captivity, and indicators of pain and psychological distress. We identify parallels between established traumatic conditions for humans and existing laboratory conditions for animals. Finally, we examine four case studies of common animal research protocols in order to illustrate research conditions that can lead to animal suffering. COMMON PAIN PATHWAYS IN HUMANS AND ANIMALS Despite the obvious challenge posed by the fact that animals are generally unable to report their physical and emotional states to humans, studies from multiple disciplines provide objective evidence of animals abilities to expe- rience pain. In fact, much of what experts understand about animal pain stems from studies in which animals were intentionally exposed to painful or distressful experiences. Partially as a result of homologous anatomical structures and physio- logical mechanisms, animals demonstrate coordinated responses to pain and many emotional states and responses that are similar to those of humans. As dened by the International Association for the Study of Pain (2007), pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (p. 1979). In its specic application to animals, Zimmermann (1986, p. 16) modied the denition to include an aversive sensory experience caused by actual or potential injury that elicits progressive motor and vegetative reactions, results in learned avoidance behavior, and may modify species-specic behavior, including social behavior. D o w n l o a d e d
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Journal of Trauma & Dissociation, 13:448468, 2012 451 Anatomical and Physiological Similarities In vertebrates, pain and proprioception are mediated by somatosensory neurons of the trigeminal and dorsal root ganglia, which terminate in the skin and other tissues. Somatosensory stimuli trigger electrical impulses that are interpreted by the central nervous system (Lumpkin & Bautista, 2005). Invertebrates have also demonstrated coordinated responses to painful stim- uli. Cephalopods, such as octopuses, demonstrate well-organized nervous systems that include brain centers concerned with sensory analysis, memory, learning, and decision making (Hochner, Shomrat, & Fiorito, 2006; Mather, 2008). These areas of the cephalopod brain have been compared with the cerebral cortex of vertebrates. As Mather (2008) has suggested, the conver- gence of brain functions of invertebrate brains to those of vertebrates may be even more relevant than anatomical comparisons. Rather than taking a scala naturae or hierarchal approach, one can explain similarities and differences in emotional processes across species by the ways in which humans and animals have adapted to different eco- logical niches (Shettleworth, 1998). Analgesics can modify pain responses in animals as they do in humans. Pain may result in physiological changes involving the heart, kidneys, immune system, and other organ systems that are critical to disease progression and recovery (Gregory, 2004). Animals can experience acute or immediate pain, as well as slow crescendo pain, such as the pain of inammation, visceral pain, and neuropathic pain. Although the nociceptive pathways of pain are fairly well described, the molecular mech- anisms involved in pain perception and the neurological responses to tissue and neuronal injury are not well understood in humans or other animals. This complicates the ability to adequately prevent, recognize, and treat pain in animals. The pain and discomfort associated with disease (also called sickness behavior) can be at least partially explained by shared cytokine- mediated responses that can result in lethargy, depression, anorexia, sleep disturbances, and enhanced sensitivity to pain (Dantzer & Kelley, 2007). Cytokines have sickness-inducing properties, partly as a result of the acti- vation of the hypothalamicpituitaryadrenal (HPA) axis. Sickness behavior occurs in mammals and birds (Dantzer & Kelley, 2007), and it is now under- stood that communication systems that link the immune and central nervous systems, although nonspecic, are biologically critical for survival and recov- ery. However, the sickness response can become maladaptive, resulting in a variety of chronic inammatory diseases and depression. Pain may be experienced differently depending on genetic and environ- mental differences. Genotype may affect susceptibility to heat or other forms of pain, and sensitivity to pain and pain-related traits may in part be heri- table (Lariviere & Mogil, 2010). Factors such as sleep deprivation have also been associated with pain perception, although the direction of causality is sometimes unclear (Lautenbacher, Kundermann, & Krieg, 2006). In addition to individual differences, other physical and psychological stressors can D o w n l o a d e d
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452 H. Ferdowsian and D. Merskin contribute signicantly to the perception of pain as well as to an individuals ability to cope with pain. Behavioral Similarities Animals express pain in ways similar to humans, including through avoidance behaviors, abnormal postures, guarding to protect an affected area, vocalizations such as whimpering, aggression, and physiological and endocrine responses, among others (Gregory, 2004). Furthermore, the antic- ipation of pain can result in mood and behavioral changes that exacerbate psychological distress (Ploghaus et al., 1999). Behavioral observations have been important in ascertaining when and how animals experience pain. However, just as there are variations in the expression of suffering within human populations, there are also differences across species and between individual animals. Because of evo- lutionary pressures, some animals may be more likely than others to use certain response behaviors. For example, many animals develop mecha- nisms that suppress signs of acute and chronic pain, particularly during times of extreme fear (Gregory, 2004; McGowan, Stubbs, & Goff, 2007). Animals vulnerable to predation may attempt to hide signs of pain in attempts to enhance survival (Moberg & Mench, 2000) but may experience psychological sequelae. Animals often exhibit fearful, avoidant, and hypervigilant behav- iors considered parallel to those expressed by traumatized humans (Cohen, Matar, Richter-Levin, & Zohar, 2006). PSYCHOLOGICAL DISTRESS AND PSYCHOPATHOLOGY The brain demonstrates signicant plasticity. Although form and function are guided by genetic factors, environment and experiences help shape brain structure, function, and activity. In anxiety and depressive disorders, the combination of stressors overwhelms normal physiological responses, sometimes causing structural and physiological changes. The structures and neuroendocrine mechanisms associated with these conditions are shared across a wide range of animals. Fear, anxiety, and relevant reactions and responses serve as an organ- isms rst line of defense (Kim & Gorman, 2005; Lang, Davis, & Ohman, 2000). Some of these responses are dependent upon the activation of a common subcortical circuit (Lang et al., 2000; Panksepp, 2004). As a result, reactions associated with fear occur much more quickly than do slower, language-based appraisals (Lang et al., 2000). The absence of certain neu- rological structures may also be relevant to suffering because animals with less organized neural circuits may demonstrate less exibility and have more limited coping mechanisms. Some animals may suffer more than humans D o w n l o a d e d
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Journal of Trauma & Dissociation, 13:448468, 2012 453 would in an analogous situation because of their inability to understand what is happening to them, make sense of their plight, escape from it, or alter their conditions. Mammals share a large number of brain regions associated with emo- tional affect, including the amygdala, hippocampus, hypothalamus, and prefrontal cortex, among other areas (Broom, 2010; Murray, 2007; Panksepp, 1982, 1998, 2004; Rolls, 2005). As a result, there are homologies in attach- ment disorders, depression, complex anxiety disorders, and persistent disorders of social behavior (Brne, 2008). For example, fear responses are stored as memories and linked to the amygdala and can be expressed in mammals as anxiety disorders and specic phobias (Brne, Brne-Cohrs, McGrew, & Preuschoft, 2006; Kim & Gorman, 2005). The hippocampus, found in all vertebrates, is involved in memory storage and retrieval and may explain some of the similarities in chronic psychopathology across species. In humans and other animals, chronic posttraumatic stress has been asso- ciated with decreased hippocampal volumes (Gregory, 2004) and changes to other areas of the brain, including the prefrontal cortex (Gregory, 2004; Otani, 2004), perhaps because of recurrently and chronically elevated lev- els of cortisol, followed by downregulation of the HPA axis (Cohen et al., 2006; Gregory, 2004). Abnormalities of the HPA axis have been identied in animals who have been conned, restrained, or isolated and after sur- gical procedures (Gregory, 2004). Moreover, studies have indicated that hypothalamic nerve growth factor levels are responsive to and modied by psychological stimuli, most likely associated with anxiety and fear (Alleva & Francia, 2009). Similar anatomical changes have also been noted across species. For example, captivity of only a few weeks duration can reduce the volume of the hippocampus of birds by as much as 23% (Tarr, Rabinowitz, Imtiaz, & DeVoogd, 2009), potentially resulting in memory decits. Variations of posttraumatic stress disorder have been described in chim- panzees and other animals (Bradshaw, Capaldo, Lindner, & Grow, 2008; Brne et al., 2006; Ferdowsian et al., 2011). Mice show persistent fear and increases in sensitized fear related to hyperarousal, emotional blunting, and social withdrawal, as seen in posttraumatic stress disorder (Siegmund & Wotjak, 2006). A study of juvenile rats designed to model childhood trauma found that exposing the rats to litter soaked in predator (cat) urine increased the likelihood that they would develop long-term behavioral disruptions thought to represent posttraumatic stress symptom equivalents. When the rats were exposed a second time in adulthood, the responses persisted (Cohen et al., 2006). Researchers have also described signs of depression in animals, includ- ing nonhuman primates, dogs, pigs, cats, birds, and rodents, among others. For example, learned helplessness and other characteristics of depres- sion, such as anhedonia, have been described in mice and other animals (Strekalova, Spanagel, Bartsch, Henn, & Gass, 2004). Mice also demonstrate D o w n l o a d e d
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454 H. Ferdowsian and D. Merskin empathic responses when painful stimuli are inicted on individuals they know (Langford et al., 2006). THE EFFECTS OF CAPTIVITY AND LABORATORY CONDITIONS Pain and distress are commonly experienced in the laboratory as a result of experimental protocols or incidentally (Balcombe, Barnard, & Sandusky, 2004; Carbone, 2004; Newcomer, 2000; Panksepp, 2004). Potential sources of pain and distress are present from birth (or even the prenatal period) to death and can include birth conditions, maternal separation, connement, cage transfers, handling, painful procedures, social isolation, restraint, and deprivation of simple needs (e.g., adequate sleep, food, water, and shel- ter). For use in research, animals are regularly transported from a breeding facility or natural habitat to a laboratory. Animals also experience social deprivation, the inability to fulll natural behaviors (e.g., hygienic practices, natural movement), lack of natural habitat, conditions of over- or understim- ulation, and witnessing of harming and killing of peers. Many of these factors resemble potentially traumatic conditions and consequences of human cap- tivity that have been described elsewhere (Brenner, 2010). Here we explore parallels between traumatic conditions for humans and common laboratory conditions for animals and explore the similar pathologies resulting from these conditions. Table 1 also illustrates cross-species parallels regarding the potential for physical and psychological trauma. Severed Bonds and Social Deprivation Animals of many species rely upon early parental support for their devel- opment. Animals also commonly form bonds with conspecics for adequate TABLE 1 Common Potential Sources of Trauma in Humans and Other Animals Physical trauma Psychological trauma Deprivation of basic needs, including water, food, sunlight, and sleep Social deprivation and neglect or social pressures Withholding of adequate nutrition Isolation or inability to seek solitude Inadequate provision of shelter, sanitation, and hygiene Sensory deprivation or overstimulation Restriction of physical activity or exercise Deprivation of the ability to fulll natural behaviors or loss of autonomy Invasive procedures, including sharp and blunt trauma, burns, induced diseases, unnecessary surgical procedures, and forms of death Threats to physical integrity or threats of death Withholding of adequate health care Witnessing of painful or distressful procedures D o w n l o a d e d
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Journal of Trauma & Dissociation, 13:448468, 2012 455 social support and development. Among both humans and animals, if a par- ent is not present early in life, offspring are likely to develop stereotypic behaviors (Bowlby, 1969, 1973, 1980; Latham & Mason, 2008). Maternally deprived animals develop a suite of changes in neurotransmitter activity and anxiety and stress responses, including increases in stereotypic behaviors (Gregory, 2004; Latham & Mason, 2008; Lutz, Well, & Novak, 2003; Mason, 2008). Although developmental periods vary widely by species, deprivation- induced stereotypic behaviors are fairly typical. It is common for laboratory animals to be separated from their mothers earlier than would be the case if they were free living (Latham & Mason, 2008). Interruption in maternal care, or restricted access to mothers who are sometimes less able to care for their young because they themselves were also maternally deprived, cre- ates distress in animals that can extend beyond infancy and adolescence. For example, laboratory mice are typically separated from their mothers at 20 days (Wrbel & Stauffacher, 1997), whereas free-living rodents are weaned around 35 days (Latham & Mason, 2004). Bar biting and other abnor- mal behaviors have been described in mice used in laboratory research as a response to premature weaning, thwarted attempts to suckle, or unpleas- ant cage experiences (Callard, Bursten, & Price, 1999; Waiblinger & Konig, 2004; Wrbel & Stauffacher, 1997). Among mouse pups, precocious wean- ing contributes to anxiety and aggression (Kikusui, Isaka, & Mori, 2005). Kittens who are removed too early from their mothers often display anxi- ety and exhibit wool-sucking behaviors (Bowen & Heath, 2005). Premature separation from mothers also leads to a range of adverse behavioral and social effects in primate infants (Dettling, Feldon, & Pryce, 2002; Harlow, Dodsworth, & Harlow, 1965; Novak, Meyer, Lutz, & Tiefenbacher, 2006; C. M. Rogers & Davenport, 1969). Stereotypic and self-directed behaviors have been described in peer-reared rhesus macaques and chimpanzees, par- ticularly those who spent their rst few months in incubators (Bloomsmith, Baker, Ross, & Pazol, 2002; Champoux, Metz, & Suomi, 1991; Erwin, 1986; Lutz et al., 2003). Prolonged Isolation and Sensory Deprivation Among humans, solitary connement is associated with increased risk for psychopathology, including symptoms of depression and anxiety (Andersen et al., 2000; Brenner, 2010). Even in conditions in which they choose to be in a temporarily isolating environment, such as polar expeditions, individuals frequently experience depression, anxiety, paranoia, and physical symptoms such as headaches and impaired cognition (Suedfeld & Steel, 2000). Animals who are purposefully bred for research or captured from the wild are routinely conned to cages prior to and during experimental pro- tocols. Cats, dogs, rodents, nonhuman primates, and other animals are D o w n l o a d e d
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456 H. Ferdowsian and D. Merskin inherently social but are frequently kept under conditions of prolonged iso- lation and sensory deprivation. As a result, animals can exhibit abnormal behaviors such as whole-body stereotypies and self-mutilation, which can be traced to maternal deprivation, connement, sensory deprivation, isola- tion, and other laboratory experiences (Avgustinovich & Kovalenko, 2005; Brne et al., 2006; Latham & Mason, 2008; Lutz et al., 2003). Standard lab- oratory housing also appears to cause changes in nonhuman primates and rodents brain regions (Kozorovitskiy et al., 2005) important to memory, such as the hippocampus. Isolation and lack of social stimulation can contribute to distress, par- ticularly among animals whose natural behaviors are highly social and involve seeking and play (Smith & Taylor, 1996). For example, tail biting, stereotypies, and neurotic behaviors are often exhibited in pigs without access to stimulation (Rollin & Kesel, 1995). Littermate-deprived kittens have demonstrated prolonged separation effects and failed to develop social com- munication skills (Guyot, Bennett, & Cross, 1980; Guyot, Cross, & Bennett, 1980). Dogs who are isolated and deprived of sensory stimulation also exhibit a variety of behavioral pathologies ranging from crying to domi- nance aggression (Gregory, 2004; Panksepp, Herman, Conner, Bishop, & Scott, 1978). Other manifestations in dogs, such as fear, generalized anxi- ety, obsessive-compulsive disorder, predatory aggression, noise phobia, and impulse control, often appear in the rst few years of life when neural systems are maturing (Overall, 1994, 2005; Overall & Dunham, 2002). Sensory Overstimulation, Sleep Deprivation, and Circadian Cycle Disruption Exposure to orescent light and disruption of sleep cycles are typical tools in the interrogation of humans (Cusick, 2006; Saar & Novak, 2005). Sounds are used for similar purposes and can result in symptoms such as ear pain, anxiety, disorientation, and disrupted cognition (Brenner, 2010, p. 473). Similarly, environmental factors such as light, human interaction, cage cleaning, sound, and transport can all inuence well-being in animals (Castelhano-Carlos & Baumans, 2009). Laboratory conditions can be noisy, bright, and confusing to animals (Rollin & Kesel, 1995). Noises common in human environments can be frightening to animals because of their lack of familiarity and animals greater sensitivity to sound (Clough, 1982). Ventilation systems, movement of equipment, human voices, vocalizations of other animals, and the operation of equipment all contribute to the stressors of the laboratory environment (Faith & Hessler, 2006). The effects of sound on human and animal neuroendocrine, cardiovascular, and sleep functions have been well documented. Loud noises can impair cardiovascular func- tion, HPA axis regulation, hippocampal and memory encoding activity, and amygdala activity (Brenner, 2010; Day, Nebel, Sasse, & Campeau, 2005; D o w n l o a d e d
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Journal of Trauma & Dissociation, 13:448468, 2012 457 Gregory, 2004). Sleep deprivation among humans and animals has been found to increase the risk for impaired immunological, cardiovascular, and cognitive performance (Caldwell & Redeker, 2005; Kales et al., 1984; N. L. Rogers, Szuba, Staab, Evans, & Dinges, 2001). For example, sleep depriva- tion has been found to cause hyperarousal in mice (Lopez-Rodriguez, Kim, & Poland, 2004) and aggressive behavior, weight loss, and adverse changes in physiological parameters in rats (Rechtschaffen & Bergmann, 2002; Webb, 1962). Sleep deprived mice and rabbits have demonstrated impairments in immune function (Toth, 1995). Threats to Physical Integrity and Life Among human political prisoners and detainees, threats of death, mock exe- cutions, exposure to extremes in temperature, connement to overly small spaces, and injuries are common torture techniques that induce signicant fear and anxiety (Brenner, 2010). Techniques such as water boarding can result in feelings of helplessness and fear of death. Likewise, intentionally exposing animals to predator threats (Cohen et al., 2006), placing them in positions in which they will be subjected to aggressive behaviors by con- specics (Van der Meer, Van Loo, & Baumans, 2004), provoking aggression, or repeating procedures that have caused physical or psychological distress in the past can cause animals to exhibit evidence of anticipatory anxiety (Pfaff, 2002). In fact, foundational experiments that led to theories of learned helplessness and clinical depression involved conditioning dogs and mice with inescapable electric shocks (Seligman, 1972; Seligman & Maier, 1967). Similar ndings have been described in other animals. CASE STUDIES We reviewed common animal research protocols to identify research condi- tions that can contribute to pain, distress, and suffering. The cases reviewed include the forced swim test commonly conducted with mice, spinal cord injury experiments in cats, cardiac pacing studies in dogs, and toxicity studies using monkeys. General details of these protocols are provided here. Furthermore, we explore some of the experimental and incidental harms associated with each research protocol, building upon the foundation provided previously. Mice: Forced Swim Test A common research protocol that uses mice is the forced swim test (see Figure 1). Although many of the primary symptoms of depression, such as low self-esteem, guilt, and suicidal ideation, are difcult or impossible D o w n l o a d e d
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458 H. Ferdowsian and D. Merskin FIGURE 1 Forced swim test. to elicit from animals (Castagn, Moser, & Porsolt, 2009), the forced swim test is commonly used in preclinical antidepressant efcacy screening protocols (Petit-Demouliere, Chenu, & Bourin, 2004). This experimental protocol is designed to demonstrate symptoms of depression, including learned helplessness, in rodents. In the forced swim test (also known as the behavioral despair test), mice are placed in containers of water of which they cannot touch the bottom or from which they cannot escape. The time rodents spend swimming, struggling, and oating is measured. Some mice struggle throughout the entire scheduled session, whereas others eventually D o w n l o a d e d
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Journal of Trauma & Dissociation, 13:448468, 2012 459 become passive and oat, moving only enough to keep their eyes and noses above water. Resignation (behavioral despair, learned helplessness) is used as a primary behavioral parameter for antidepressant activity (Porsolt, Brossard, Hautbois, & Roux, 2001). Periods of immobility are measured in relationship to pharmaceutical intervention. As a result of the forced swim test, researchers have reported profound chronic changes in biological and behavioral parameters in rodents (Becker et al., 2008). Behavioral despair, induced hyperactivity of the HPA axis, loss of body weight, and hypothermia often occur after the stress of the proto- col. The prolonged immobility of the forced swim test amplies feelings of helplessness. Cats: Spinalization Cats are used in spinal cord injury experiments, in which they are anes- thetized and intubated while a laminectomy is performed (Marcoux & Rossignol, 2000). The cats spinal cords are then severed with surgical scis- sors and an absorbable hemostat is placed to ll the space, followed by suturing of the wound. The wounds remain partially open to reveal the spinal cord, and S-hooks are attached through which pressure is admin- istered to approximate weight-bearing loads. The cats awaken paralyzed. After surgical intervention, the cats are placed in individual cages, with daily interventions including manual bladder expression and cleaning of their hindquarters. Dogs: Ventricular Pacing Dogs are used in ventricular pacing studies, in which their heart rates are elevated for extended periods of time to approximate heart failure in humans. Although the normal heart rate for adult dogs is 70120 beats per minute, cardiac pacing protocols dictate rapid pacing from 130 to more than 600 beats per minute (Ahlberg, Ripplinger, Skadsberg, Iaizzo, & Mulligan, 2007; Everett et al., 2000; Khoury et al., 2009). Tachycardia is maintained, in some cases for days and weeks at a time. Protocols include surgical inter- vention, instrumentation, rapid atrial or ventricular pacing, pharmacological intervention, and euthanasia. Cardiovascular consequences include severe ventricular arrhythmias, changes in hemodynamic parameters (e.g., blood pressure and vascular resistance), physiological changes (e.g., heart rate, car- diac output, stroke volume, contractility and relaxation), and death (Ahlberg et al., 2007; Everett et al., 2000; Khoury et al., 2009). Monkeys: Toxicology Tests Monkeys are commonly used in toxicity tests in order to estimate the poten- tial effects in and risks to humans (Dorato & Buckley, 2006; Gad, 2009; D o w n l o a d e d
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460 H. Ferdowsian and D. Merskin Grote-Wessels, Frings, Smith, & Weinbauer, 2009; Korte, Vogel, & Osterburg, 1987). A typical method for studying acute systemic toxicity among primates is a pyramiding dosage design (Gad, 2009, p. 215). Drugs are administered in escalating amounts via oral, intravenous, and pulmonary routes, including gavage. Monkeys are exposed to the highest tolerable levels (Hayes, 2007, p. 1608), although death, particularly in reproductive and developmental toxicology studies, is not unusual (Buse, Habermann, Osterburg, Korte, & Weinbauer, 2003; Martin & Weinbauer, 2010). Monkey fetuses and infants are used to investigate drug effects on organogenesis; toxic doses are typically administered to the mothers during pregnancy or lactation. Mothers are captured from the wild or purposefully bred, shipped, caged, and repeatedly handled in the laboratory. Their offspring often abort or die early. If infants survive, they are typically taken from their mothers shortly after birth. In one protocol, colony-bred adult female rhesus monkeys were purchased from China for use in Japan, where the monkeys were kept in stainless steel cages (Yasuda et al., 2005). Male monkeys were housed with female monkeys on Days 12, 13, and 14 of the female monkeys menstrual cycles in order to induce sexual intercourse and pregnancy. Pregnancy was conrmed with ultrasound after monkeys were anesthetized with ketamine. Subsequently, pregnant mothers were weighed every 20 days and injected with varying dosage levels of dioxin. Once the babies were delivered, they lived with their mothers for 1 year and were exposed to dioxin through breast milk. The young monkeys were weighed every 10 days, then euthanized, so researchers could examine morbidity and mortality associated with dioxin exposure. Morbidity included severe dental disease. DISCUSSION The examples presented here highlight research conditions that can con- tribute to pain, distress, and suffering. In addition to the pain and distress associated with experimental protocols, animals also experience pain, distress, and suffering as a result of routine aspects of the laboratory environment. Thwarted opportunities to fulll and express species-specic behaviors can also result in suffering (Jensen & Toates, 1993; Rollin, 2010). All of the cases described here include the potential for experimental and incidental harms, such as severed bonds and social deprivation, isola- tion and sensory deprivation, the inability to fulll natural behaviors, and threats to animals physical integrity and lives. For example, mice used in forced swim test protocols experience near-drowning and hypothermia as well as sleep disruption and depression (which are goals of the experimen- tal intervention), shipment, frequent handling and cage transfers, instrument placement, and connement. D o w n l o a d e d
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Journal of Trauma & Dissociation, 13:448468, 2012 461 Likewise, spinal cord injury experiments expose cats to many of the incidental harms incurred by mice in addition to life-threatening complica- tions of spinal cord injury, including infection and shock. Cats are placed in single-cage housing and prevented from fullling natural behaviors, lack solitude and privacy, and are incapable of performing normal hygienic practices. Dogs also experience pain, distress, and suffering as a result of their use in heart failure experiments. Like cats and mice, dogs are prevented from forming normal bonds and engaging in normal socialization. Dogs experi- ence threats to their physical integrity and lives (rapid ventricular pacing and heart failure), overstimulation, disruption of natural sleep cycles, and an inability to control or stop the pain and discomfort associated with the protocol. Monkeys also experience experimental and incidental harms as a result of their use in toxicology experiments. Experimental harms include severe pain and repeated threats to their physical integrity and lives. Incidental harms include conditions of capture and breeding, maternal separation and deprivation, isolation, and transport, among others. These monkeys and their offspring are also unable to fulll natural behaviors such as socialization and exploration. CONCLUSIONS Anatomical, physiological, and behavioral similarities across species demon- strate that animals experience pain and distress in ways similar or identical to humans. There are also commonalities in the factors that contribute to pain, distress, and suffering in humans and other animals. Furthermore, animals vulnerability and dependence on humans while in captivity likely contribute to their suffering. Although researchers can never be certain of the details of the expe- riences of other animals, or even other humans, animals have necessary and sufcient structures, systems, and mechanisms from which pain, dis- tress, and suffering can occur. We have not exhausted the list of potential harms to animals as a result of their use in laboratory research. Rather, our goal was to consider and illustrate shared conditions of suffering among humans and other animals. It is also worth noting that, just as human sur- vivors react and recover in a range of ways, depending on their severity of exposure, developmental level, support systems, coping mechanisms, and recovery environment, so may animals in certain circumstances. Not all indi- viduals experience long-term physical or psychological sequelae of trauma. Nevertheless, it is the potential for physical and psychological trauma that inevitably contributes to the ethical considerations regarding the use of ani- mals in research. These ndings also have implications regarding other ways in which animals are used by humans. D o w n l o a d e d
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