Pain in animals

From Wikipedia, the free encyclopedia
Jump to: navigation, search
A Galapagos shark hooked by a fishing boat

In humans, pain is a distressing feeling often caused by intense or damaging stimuli. Whether animals apart from humans also experience pain is contentious. The standard measure of pain in humans is how a person reports that pain, (for example, on a pain scale). "Pain" is defined by the International Association for the Study of Pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage."[1] Only the person experiencing the pain can know the pain's quality and intensity, and the degree of suffering. However, for non-human animals, it is harder, if even possible, to know whether an emotional experience has occurred.[2] Therefore, this concept is often excluded in definitions of pain in animals, such as that provided by Zimmerman: "an aversive sensory experience caused by actual or potential injury that elicits protective motor and vegetative reactions, results in learned avoidance and may modify species-specific behaviour, including social behaviour."[3] Non-human animals cannot report their feelings to language-using humans in the same manner as human communication, but observation of their behaviour provides a reasonable indication as to the extent of their pain. Just as with doctors and medics who sometimes share no common language with their patients, the indicators of pain can still be understood.

According to the U.S. National Research Council Committee on Recognition and Alleviation of Pain in Laboratory Animals, pain is experienced by many animal species, including mammals and possibly all vertebrates.[4]

The experience of pain[edit]

Although there are numerous definitions of pain, almost all involve two key components. First, nociception is required.[5] This is the ability to detect noxious stimuli which evoke a reflex response that rapidly moves the entire animal, or the affected part of its body, away from the source of the stimulus. The concept of nociception does not imply any adverse, subjective "feeling" – it is a reflex action. An example in humans would be the rapid withdrawal of a finger that has touched something hot – the withdrawal occurs before any sensation of pain is actually experienced.

The second component is the experience of "pain" itself, or suffering – the internal, emotional interpretation of the nociceptive experience. Again in humans, this is when the withdrawn finger begins to hurt, moments after the withdrawal. Pain is therefore a private, emotional experience. Pain cannot be directly measured in other animals, including other humans; responses to putatively painful stimuli can be measured, but not the experience itself. To address this problem when assessing the capacity of other species to experience pain, argument-by-analogy is used. This is based on the principle that if an animal responds to a stimulus in a similar way to ourselves, it is likely to have had an analogous experience.

Reflex response to painful stimuli[edit]

Reflex arc of a dog with when her paw is stuck with a pin. The spinal cord responds to signals from receptors in the paw, producing a reflex withdrawal of the paw. This localized response does not involve brain processes that might mediate a consciousness of pain, though these might also occur.

Nociception usually involves the transmission of a signal along nerve fibers from the site of a noxious stimulus at the periphery to the spinal cord. Although this signal is also transmitted on to the brain, a reflex response, such as flinching or withdrawal of a limb, is produced by return signals originating in the spinal cord. Thus, both physiological and behavioral responses to nociception can be detected, and no reference need be made to a conscious experience of pain. Based such criteria nociception has been observed in all major animal taxa.[5]

Awareness of pain[edit]

Nerve impulses from nociceptors may reach the brain, where information about the stimulus (e.g. quality, location, and intensity), and affect (unpleasantness) are registered. Though the brain activity involved has been studied, the brain processes underlying conscious awareness are not well understood.

Adaptive value[edit]

The adaptive value of nociception is obvious; an organism detecting a noxious stimulus immediately withdraws the limb, appendage or entire body from the noxious stimulus and thereby avoids further (potential) injury. However, a characteristic of pain (in mammals at least) is that pain can result in hyperalgesia (a heightened sensitivity to noxious stimuli) and allodynia (a heightened sensitivity to non-noxious stimuli). When this heightened sensitisation occurs, the adaptive value is less clear. First, the pain arising from the heightened sensitisation can be disproportionate to the actual tissue damage caused. Second, the heightened sensitisation may also become chronic, persisting well beyond the tissues healing. This can mean that rather than the actual tissue damage causing pain, it is the pain due to the heightened sensitisation that becomes the concern. This means the sensitisation process is sometimes termed maladaptive. It is often suggested hyperalgesia and allodynia assist organisms to protect themselves during healing, but experimental evidence to support this has been lacking.[6][7]

In 2014, the adaptive value of sensitisation due to injury was tested using the predatory interactions between longfin inshore squid (Doryteuthis pealeii) and black sea bass (Centropristis striata) which are natural predators of this squid. If injured squid are targeted by a bass, they began their defensive behaviours sooner (indicated by greater alert distances and longer flight initiation distances) than uninjured squid. If anaesthetic (1% ethanol and MgCl2) is administered prior to the injury, this prevents the sensitisation and blocks the behavioural effect. The authors claim this study is the first experimental evidence to support the argument that nociceptive sensitisation is actually an adaptive response to injuries.[8]

Argument-by-analogy[edit]

To assess the capacity of other species to consciously suffer pain we resort to argument-by-analogy. That is, if an animal responds to a stimulus the way a human does, it is likely to have had an analogous experience. If we stick a pin in a chimpanzee's finger and she rapidly withdraws her hand, we use argument-by-analogy and infer that like us, she felt pain. It might be argued that consistency requires us infer, also, that a cockroach experiences conscious pain when it writhes after being stuck with a pin. The usual counter-argument is that although the physiology of consciousness is not understood, it clearly involves complex brain processes not present in relatively simple organisms.[9] Other analogies have been pointed out. For example, when given a choice of foods, rats[10] and chickens[11] with clinical symptoms of pain will consume more of an analgesic-containing food than animals not in pain. Additionally, the consumption of the analgesic carprofen in lame chickens was positively correlated to the severity of lameness, and consumption resulted in an improved gait. Such anthropomorphic arguments face the criticism that physical reactions indicating pain may be neither the cause nor result of conscious states.

History[edit]

The idea that animals might not experience pain or suffering as humans do traces back at least to the 17th-century French philosopher, René Descartes, who argued that animals lack consciousness.[12][13][14] Researchers remained unsure into the 1980s as to whether animals experience pain, and veterinarians trained in the U.S. before 1989 were simply taught to ignore animal pain.[15] In his interactions with scientists and other veterinarians, Bernard Rollin was regularly asked to "prove" that animals are conscious, and to provide "scientifically acceptable" grounds for claiming that they feel pain.[15] Some authors say that the view that animals feel pain differently is now a minority view.[12] Academic reviews of the topic are more equivocal, noting that, although it is likely that some animals have at least simple conscious thoughts and feelings,[16] some authors continue to question how reliably animal mental states can be determined.[13][17]

In different species[edit]

The ability to experience pain in an animal, or another human for that matter, cannot be determined directly but it may be inferred through analogous physiological and behavioral reactions.[18] Although many animals share similar mechanisms of pain detection to those of humans, have similar areas of the brain involved in processing pain, and show similar pain behaviours, it is notoriously difficult to assess how animals actually experience pain.[19]

Nociception[edit]

Nociceptive nerves, which preferentially detect (potential) injury-causing stimuli, have been identified in a variety of animals, including invertebrates. The medicinal leech, Hirudo medicinalis, and sea slug are classic model systems for studying nociception.[19] Many other vertebrate and invertebrate animals also show nociceptive reflex responses similar to our own.

Pain[edit]

Many animals also exhibit more complex behavioural and physiological changes indicative of the ability to experience pain: they eat less food, their normal behaviour is disrupted, their social behaviour is suppressed, they may adopt unusual behaviour patterns, they may emit characteristic distress calls, experience respiratory and cardiovascular changes, as well as inflammation and release of stress hormones.[19]

Some criteria that may indicate the potential of another species to feel pain include:[20]

  1. Has a suitable nervous system and sensory receptors
  2. Physiological changes to noxious stimuli
  3. Displays protective motor reactions that might include reduced use of an affected area such as limping, rubbing, holding or autotomy
  4. Has opioid receptors and shows reduced responses to noxious stimuli when given analgesics and local anaesthetics
  5. Shows trade-offs between stimulus avoidance and other motivational requirements
  6. Shows avoidance learning
  7. High cognitive ability and sentience

Vertebrates[edit]

Fish[edit]

A typical human cutaneous nerve contains 83% C type trauma receptors (the type responsible for transmitting signals described by humans as excruciating pain); the same nerves in humans with congenital insensitivity to pain have only 24-28% C type receptors.[21] The rainbow trout has about 5% C type fibres, while sharks and rays have 0%.[22] Nevertheless, fish have been shown to have sensory neurons that are sensitive to damaging stimuli and are physiologically identical to human nociceptors.[23] Behavioural and physiological responses to a painful event appear comparable to those seen in amphibians, birds, and mammals, and administration of an analgesic drug reduces these responses in fish.[24]

Animal welfare advocates have raised concerns about the possible suffering of fish caused by angling. Some countries, e.g. Germany, have banned specific types of fishing, and the British RSPCA now formally prosecutes individuals who are cruel to fish.[25]

Invertebrates[edit]

Though it has been argued that most invertebrates do not feel pain,[26][27][28] there is some evidence that invertebrates, especially the decapod crustaceans (e.g. crabs and lobsters) and cephalopods (e.g. octopuses), exhibit behavioural and physiological reactions indicating they may have the capacity for this experience.[9][29][30] Nociceptors have been found in nematodes, annelids and molluscs.[31] Most insects do not possess nociceptors,[32][33][34] one known exception being the fruit fly.[35] In vertebrates, endogenous opioids are neurochemicals that moderate pain by interacting with opiate receptors. Opioid peptides and opiate receptors occur naturally in nematodes,[36][37] molluscs,[38][39] insects[40][41] and crustaceans.[42][43] The presence of opioids in crustaceans has been interpreted as an indication that lobsters may be able to experience pain, although it has been claimed "at present no certain conclusion can be drawn".[44]

One suggested reason for rejecting a pain experience in invertebrates is that invertebrate brains are too small. However, brain size does not necessarily equate to complexity of function.[45] Moreover, weight for body-weight, the cephalopod brain is in the same size bracket as the vertebrate brain, smaller than that of birds and mammals, but as big as or bigger than most fish brains.[46][47]

Since September 2010, all cephalopods being used for scientific purposes in the EU are protected by EU Directive 2010/63/EU which states "...there is scientific evidence of their [cephalopods] ability to experience pain, suffering, distress and lasting harm.[48] In the UK, animal protection legislation[49] means that cephalopods used for scientific purposes must be killed humanely, according to prescribed methods (known as "Schedule 1 methods of euthanasia") known to minimise suffering.[50]

In medicine and research[edit]

Veterinary medicine[edit]

Veterinary medicine uses, for actual or potential animal pain, the same analgesics and anesthetics as used in humans.[51]

Dolorimetry[edit]

Dolorimetry (dolor: Latin: pain, grief) is the measurement of the pain response in animals, including humans. It is practiced occasionally in medicine, as a diagnostic tool, and is regularly used in research into the basic science of pain, and in testing the efficacy of analgesics. Non-human animal pain measurement techniques include the paw pressure test, tail flick test, hot plate test and grimace scales.

Laboratory animals[edit]

Animals are kept in laboratories for a wide range of reasons, some of which may involve pain, suffering or distress, whilst others (e.g. many of those involved in breeding) will not. The extent to which animal testing causes pain and suffering in laboratory animals is the subject of much debate.[52] Marian Stamp Dawkins defines "suffering" in laboratory animals as the experience of one of "a wide range of extremely unpleasant subjective (mental) states."[53] The U.S. National Research Council has published guidelines on the care and use of laboratory animals,[54] as well as a report on recognizing and alleviating pain in vertebrates.[55] The United States Department of Agriculture defines a "painful procedure" in an animal study as one that would "reasonably be expected to cause more than slight or momentary pain or distress in a human being to which that procedure was applied."[56] Some critics argue that, paradoxically, researchers raised in the era of increased awareness of animal welfare may be inclined to deny that animals are in pain simply because they do not want to see themselves as people who inflict it.[57] PETA however argues that there is no doubt about animals in laboratories being inflicted with pain.[58] In the UK, animal research likely to cause "pain, suffering, distress or lasting harm" is regulated by the Animals (Scientific Procedures) Act 1986 and research with the potential to cause pain is regulated by the Animal Welfare Act of 1966 in the US.

In the U.S., researchers are not required to provide laboratory animals with pain relief if the administration of such drugs would interfere with their experiment. Laboratory animal veterinarian Larry Carbone writes, “Without question, present public policy allows humans to cause laboratory animals unalleviated pain. The AWA, the Guide for the Care and Use of Laboratory Animals, and current Public Health Service policy all allow for the conduct of what are often called “Category E” studies – experiments in which animals are expected to undergo significant pain or distress that will be left untreated because treatments for pain would be expected to interfere with the experiment.”[59]

Severity scales[edit]

Eleven countries have national classification systems of pain and suffering experienced by animals used in research: Australia, Canada, Finland, Germany, The Republic of Ireland, The Netherlands, New Zealand, Poland, Sweden, Switzerland, and the UK. The US also has a mandated national scientific animal-use classification system, but it is markedly different from other countries in that it reports on whether pain-relieving drugs were required and/or used.[60] The first severity scales were implemented in 1986 by Finland and the UK. The number of severity categories ranges between 3 (Sweden and Finland) and 9 (Australia). In the UK, research projects are classified as "mild", "moderate", and "substantial" in terms of the suffering the researchers conducting the study say they may cause; a fourth category of "unclassified" means the animal was anesthetized and killed without recovering consciousness. It should be remembered that in the UK system, many research projects (e.g. transgenic breeding, feeding distasteful food) will require a license under the Animals (Scientific Procedures) Act 1986, but may cause little or no pain or suffering. In December 2001, 39 percent (1, 296) of project licenses in force were classified as "mild", 55 percent (1, 811) as "moderate", two percent (63) as "substantial", and 4 percent (139) as "unclassified".[61] In 2009, of the project licenses issued, 35 percent (187) were classified as "mild", 61 percent (330) as "moderate", 2 percent (13) as "severe" and 2 percent (11) as unclassified.[62]

In the US, the Guide for the Care and Use of Laboratory Animals defines the parameters for animal testing regulations. It states, "The ability to experience and respond to pain is widespread in the animal kingdom...Pain is a stressor and, if not relieved, can lead to unacceptable levels of stress and distress in animals. "[63] The Guide states that the ability to recognize the symptoms of pain in different species is essential for the people caring for and using animals. Accordingly, all issues of animal pain and distress, and their potential treatment with analgesia and anesthesia, are required regulatory issues for animal protocol approval.

See also[edit]

References[edit]

  1. ^ IASP Pain Terminology
  2. ^ Andrew right, A Criticism of the IASP's Definition of Pain, http://www.academia.edu/1388768/A_Criticism_of_the_IASPs_Definition_of_Pain
  3. ^ Zimmerman, M (1986). "Physiological mechanisms of pain and its treatment". Klinische Anaesthesiol Intensivether. 32: 1–19. 
  4. ^ National Research Council (US) Committee on Recognition and Alleviation of Pain in Laboratory Animals (2009). "Recognition and Alleviation of Pain in Laboratory Animals". National Center for Biotechnology Information. Retrieved 14 Feb 2015. 
  5. ^ a b Sneddon, L.U. (2004). "Evolution of nociception in vertebrates: comparative analysis of lower vertebrates". Brain Research Reviews. 46: 123–130. doi:10.1016/j.brainresrev.2004.07.007. 
  6. ^ Price, T.J. & Dussor, G. (2014). "Evolution: the advantage of ‘maladaptive’pain plasticity". Current Biology. 24 (10): R384–R386. PMC 4295114Freely accessible. PMID 24845663. doi:10.1016/j.cub.2014.04.011. 
  7. ^ "Maladaptive pain". Oxford Reference. Retrieved May 16, 2016. 
  8. ^ Crook, R.J., Dickson, K., Hanlon, R.T. and Walters, E.T. (2014). "Nociceptive sensitization reduces predation risk". Current Biology. 24 (10): 1121–1125. doi:10.1016/j.cub.2014.03.043. 
  9. ^ a b Sherwin, C.M. (2001). Can invertebrates suffer? Or, how robust is argument-by-analogy? Animal Welfare, 10(supplement): 103-118
  10. ^ Colpaert, F.C.; Tarayre, J.P.; Alliaga, M.; Slot, L.A.B.; Attal, N.; Koek, W. (2001). "Opiate self-administration as a measure of chronic nociceptive pain in arthritic rats". Pain. 91: 33–45. doi:10.1016/s0304-3959(00)00413-9. 
  11. ^ Danbury, T.C.; Weeks, C.A.; Chambers, J.P.; Waterman-Pearson, A.E.; Kestin, S.C. (2000). "Self-selection of the analgesic drug carprofen by lame broiler chickens". Veterinary Record. 14: 307–311. 
  12. ^ a b Carbone, Larry. '"What Animal Want: Expertise and Advocacy in Laboratory Animal Welfare Policy. Oxford University Press, 2004, p. 149.
  13. ^ a b The Ethics of research involving animals Nuffield Council on Bioethics, Accessed 27 February 2008 Archived 27 February 2008 at the Wayback Machine.
  14. ^ Talking Point on the use of animals in scientific research, EMBO reports 8, 6, 2007, pp. 521–525
  15. ^ a b Rollin, Bernard. The Unheeded Cry: Animal Consciousness, Animal Pain, and Science. New York: Oxford University Press, 1989, pp. xii, 117-118, cited in Carbone 2004, p. 150.
  16. ^ Griffin, DR; Speck, GB (2004). "New evidence of animal consciousness." (PDF). Animal Cognition. 7 (1): 5–18. PMID 14658059. doi:10.1007/s10071-003-0203-x. 
  17. ^ Allen C (1998). "Assessing animal cognition: ethological and philosophical perspectives" (PDF). J. Anim. Sci. 76 (1): 42–7. PMID 9464883. 
  18. ^ Abbott FV, Franklin KB, Westbrook RF (January 1995). "The formalin test: scoring properties of the first and second phases of the pain response in rats". Pain. 60 (1): 91–102. PMID 7715946. doi:10.1016/0304-3959(94)00095-V. 
  19. ^ a b c Sneddon, Lynne. "Can animals feel pain?". PAIN. Retrieved 18 March 2012. 
  20. ^ Elwood, R.W.; Barr, S.; Patterson, L. (2009). "Pain and stress in crustaceans?". Applied Animal Behaviour Science. 118 (3): 128–136. doi:10.1016/j.applanim.2009.02.018. 
  21. ^ Rose, JD; Arlinghaus, R; Cooke, SJ; Diggles, BK; Sawynok, W; Stevens, ED; Wynne, CDL (2012). "Can fish really feel pain?" (PDF). Fish and Fisheries. 15 (1): 97–133. doi:10.1111/faf.12010. 
  22. ^ Snow, P.J.; Plenderleith, M.B.; Wright, L.L. (1993). "Quantitative study of primary sensory neurone populations of three species of elasmobranch fish". Journal of Comparative Neurology. 334: 97–103. doi:10.1002/cne.903340108. 
  23. ^ L.U. Sneddon; et al. "Do fishes have nociceptors? Evidence for the evolution of a vertebrate sensory system.". Proc Biol Sci. 270: 1115–21. PMC 1691351Freely accessible. PMID 12816648. doi:10.1098/rspb.2003.2349. 
  24. ^ Sneddon L (2009). "Pain and Distress in Fish". ILAR J. 50 (4): 338–342. doi:10.1093/ilar.50.4.338. 
  25. ^ Leake, J. (March 14, 2004). "Anglers to Face RSPCA Check". The Sunday Times. Retrieved September 15, 2015. 
  26. ^ Eisemann C, Jorgensen W, Rice D, Cribb M, Zalucki M, Merritt B, Webb P (1984). "Do insects feel pain? - A biological view" (PDF). Experentia. 40: 164–167. doi:10.1007/bf01963580. 
  27. ^ "Do Invertebrates Feel Pain?", The Senate Standing Committee on Legal and Constitutional Affairs, The Parliament of Canada Web Site, accessed 11 June 2008.
  28. ^ Jane A. Smith (1991). "A question of pain in invertebrates". ILAR Journal. 33 (1–2). 
  29. ^ Elwood, R.W. (2011). "Pain and suffering in invertebrates?" (PDF). Institute of Laboratory Animal Resources Journal. 52 (2): 175–84. 
  30. ^ Fiorito, G. (1986). "Is there pain in invertebrates?". Behavioural Processes. 12 (4): 383–388. doi:10.1016/0376-6357(86)90006-9. 
  31. ^ St John Smith, E.; Lewin, G.R. (2009). "Nociceptors: a phylogenetic view". Journal of Comparative Physiology A Neuroethology Sensory Neural and Behavioral Physiology. 195: 1089–1106. doi:10.1007/s00359-009-0482-z. 
  32. ^ DeGrazia D, Rowan A (1991). "Pain, suffering, and anxiety in animals and humans". Theoretical Medicine and Bioethics. 12 (3): 193–211. PMID 1754965. doi:10.1007/BF00489606. 
  33. ^ Lockwood JA (1987). "The moral standing of insects and the ethics of extinction". The Florida Entomologist. 70 (1): 70–89. JSTOR 3495093. doi:10.2307/3495093. 
  34. ^ Eisemann C. H.; Jorgensen W. K.; Merritt D. J.; Rice M. J.; Cribb B. W.; Webb P. D.; Zalucki M. P. (1984). "Do insects feel pain? — A biological view". Experientia. 40: 164–7. doi:10.1007/bf01963580. 
  35. ^ Tracey, J., W. Daniel, R. I. Wilson, G. Laurent, and S. Benzer. (2003). "painless, a Drosophila gene essential for nociception.". Cell. 113 (2): 261–273. PMID 12705873. doi:10.1016/S0092-8674(03)00272-1. 
  36. ^ Wittenburg, N.; Baumeister, R. (1999). "Thermal avoidance in Caenorhabditis elegans: an approach to the study of nociception". Proceedings of the National Academy of Sciences USA. 96: 10477–10482. doi:10.1073/pnas.96.18.10477. 
  37. ^ Pryor, S.C., Nieto, F., Henry, S. and Sarfo, J. (2007). "The effect of opiates and opiate antagonists on heat latency response in the parasitic nematode Ascaris suum.". Life Sciences. 80: 1650–1655. PMID 17363006. doi:10.1016/j.lfs.2007.01.011. 
  38. ^ Dalton, L.M.; Widdowson, P.S. (1989). "The involvement of opioid peptides in stress-induced analgesia in the slug Arion ater". Peptides. 10: 9–13. doi:10.1016/0196-9781(89)90067-3. 
  39. ^ Kavaliers, M.; Ossenkopp, K.-P. (1991). "Opioid systems and magnetic field effects in the land snail, Cepaea nemoralis". Biological Bulletin. 180: 301–309. doi:10.2307/1542401. 
  40. ^ Dyakonova, V.E.; Schurmann, F.; Sakharov, D.A. (1999). "Effects of serotonergic and opioidergic drugs on escape behaviors and social status of male crickets". Naturwissenschaften. 86: 435–437. doi:10.1007/s001140050647. 
  41. ^ Zabala, N.; Gomez, M. (1991). "Morphine analgesia, tolerance and addiction in the cricket, Pteronemobius". Pharmacology, Biochemistry and Behaviour. 40: 887–891. doi:10.1016/0091-3057(91)90102-8. 
  42. ^ Lozada, M.; Romano, A.; Maldonado, H. (1988). "Effect of morphine and naloxone on a defensive response of the crab Chasmagnathus granulatus". Pharmacology, Biochemistry and Behavior. 30: 635–640. doi:10.1016/0091-3057(88)90076-7. 
  43. ^ Maldonado, H.; Miralto, A. (1982). "Effects of morphine and naloxone on a defensive response of the mantis shrimp (Squilla mantis)". Journal of Comparative Physiology A. 147: 455–459. doi:10.1007/bf00612010. 
  44. ^ L. Sømme (2005). "Sentience and pain in invertebrates: Report to Norwegian Scientific Committee for Food Safety". Norwegian University of Life Sciences, Oslo. 
  45. ^ Chittka, L.; Niven, J. (2009). "Are Bigger Brains Better?". Current Biology. 19 (21): R995–R1008. PMID 19922859. doi:10.1016/j.cub.2009.08.023. 
  46. ^ Cephalopod brain size
  47. ^ Packard, A (1972). "Cephalopods and fish: the limits of convergence". Biological Reviews. 47: 241–307 [266–7]. doi:10.1111/j.1469-185X.1972.tb00975.x. 
  48. ^ "Directive 2010/63/EU of the European Parliament and of the Council". Article 1, 3(b) (see page 276/39): Official Journal of the European Union. Retrieved April 17, 2016. 
  49. ^ "Animals (Scientific Protection) Act 1986". Retrieved April 18, 2016. 
  50. ^ "The Animals (Scientific Procedures) Act 1986 Amendment Regulations 2012". Retrieved April 15, 2016. 
  51. ^ Viñuela-Fernández I, Jones E, Welsh EM, Fleetwood-Walker SM (September 2007). "Pain mechanisms and their implication for the management of pain in farm and companion animals". Vet. J. 174 (2): 227–39. PMID 17553712. doi:10.1016/j.tvjl.2007.02.002. 
  52. ^ Duncan, IJ; Petherick, JC (December 1991). "The implications of cognitive processes for animal welfare". J. Anim. Sci. 69: 5017–22. PMID 1808195. doi:10.2527/1991.69125017x. ; Curtis, SE; Stricklin, WR (1991). "The importance of animal cognition in agricultural animal production systems: an overview". J. Anim. Sci. 69 (12): 5001–7. PMID 1808193. doi:10.2527/1991.69125001x. 
  53. ^ Stamp Dawkins, Marian. "Scientific Basis for Assessing Suffering in Animals," in Singer, Peter. In Defense of Animals: The Second Wave. Blackwell, 2006. p. 28.
  54. ^ Committee for the Update of the Guide for the Care and Use of Laboratory Animals, ed. (2011). Guide for the Care and Use of Laboratory Animals (Report) (8th ed.). The National Academies Press. 
  55. ^ National Research Council, Division on Earth and Life Studies, Committee on Recognition and Alleviation of Pain in Laboratory Animals (2009). Recognition and Alleviation of Pain in Laboratory Animals (PDF) (Report). The National Academies Press. 
  56. ^ Animal Welfare; Definitions for and Reporting of Pain and Distress", Animal Welfare Information Center Bulletin, Summer 2000, Vol. 11 No. 1-2, United States Department of Agriculture.
  57. ^ Carbone 2004, p. 151.
  58. ^ http://www.peta.org/issues/animals-used-for-experimentation/animals-in-laboratories.aspx
  59. ^ Carbone, L (7 September 2011). "Pain in Laboratory Animals: The Ethical and Regulatory Imperatives". PLOS ONE. 6 (9): e21578. PMC 3168441Freely accessible. PMID 21915253. doi:10.1371/journal.pone.0021578. Retrieved 14 July 2015. 
  60. ^ Fenwick, N.; Ormandy, E.; Gauthier, C.; Griffin, G. (2011). "Classifying the severity of scientific animal use: a review of international systems". Animal Welfare. 20: 281–301. 
  61. ^ Ryder, Richard D. "Speciesism in the laboratory, " in Singer, Peter. In Defense of Animals: The Second Wave. Blackwell, 2006. p. 99.
  62. ^ "Home Office Statistics". Archived from the original on 22 September 2011. Retrieved 31 October 2011. 
  63. ^ Guide for the Care and Use of Laboratory Animals, ILAR, National Research Council, 1996 copyright, pg 64