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Index A American College of Veterinary Anesthiologists, 72 Abdominal pain. See Visceral/abdominal American Veterinary Medical Association, pain 37-38, 131, 162 Acepromazine, 75, 85 Amphibians, 2, 21, 22, 63, 81, 101, Acetaminophen, 82, 104 105 Acupuncture, 89, 90 Analgesics and anesthetics. See also Acute pain. See Momentary pain; indiidual drugs Postprocedural and postsurgical pain adjuvant therapy, 77, 93 Adjuvant therapy, 77, 93 advanced techniques, 77-78, 79 Affect/affective states, 14 α2-adrenoreceptor antagonists, 91 brain imaging, 56 α2-adrenoreceptor agonists, 75, 76, 78, CNS anatomy, 36 79, 84-85, 87, 91, 93, 101 and consciousness/awareness, 18 and assessment of pain, 51 defined, xi, 18 behavioral effects, 51, 54, 80-81 modulation of pain, 42-43 and body weight, 51 Aggressive behavior, 57-58, 59, 61, 95 cardioprotective drugs, 87-88 Agricultural Chemical Safety Assessment confounding and beneficial effects, 4, committee, 126 51, 54, 83, 85-89, 103, 148 Allodynia, xi, 36, 38-39, 56, 84, 95, 150, depth of anesthesia, 74 151, 152, 154 dosage, administration route, and α2-Adrenoreceptor agonists, 75, 76, 77, 79, efficacy, 50-51, 55-56, 72, 73, 76, 84-85, 93, 101 79-85, 92, 96, 100-101, 104 α-Chloralose, 74, 76 extrapolation from other species, 3, 43, Alternatives to minimize animal use, 125, 55, 81, 83, 99, 101, 102, 105 126-127, 129, 161 general anesthesia, 19, 37, 38, 73-75, Alzheimer’s disease, 87 88, 91, 96 American College of Laboratory Animal immunosuppression and reduction of Medicine, 164-165 inflammatory response, 66-69 Animal Welfare Act, 26, 159-160, intensity of pain and, 78 164-165 11

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12 INDEX local anesthetics, xi, 60, 72, 73, 76, 77, postoperative (incisional), 98-99, 145, 78, 79, 83, 89, 91-92, 93, 96, 97, 149, 154 101, 106, 126, 127 rationale for, 143 monitoring effectiveness of, 72 spontaneous, 98-99, 153-154 multimodal regimens, 72, 74-75, 77, 78, visceral, 52, 82, 144-145, 148-149, 154 81, 82-83, 84, 87, 94, 96 Animal welfare. See also Humane naturally produced by the body, 80, 92 endpoints; The Three Rs neuroprotective drugs, 87 agricultural practices, 60 neurotoxicity, 86-87 alternatives to minimize animal use, NMDA receptor antagonists, 76, 77, 78, 125, 126-127, 129, 161 84, 86, 87, 94, 95, 96, 97 ethical justification for pain, 11, 26-27, NSAIDs, 20, 39, 51, 52, 76, 77, 78, 79, 71 82-83, 93, 94, 96, 97, 99, 100, 101, pain management in persistent pain 102, 103, 104, 152 models, 98-99 opioids, xi, 24, 41, 51, 52, 54, 63, 72, public expectations, 11 75, 76, 77, 78, 79, 80-81, 84, 88, 89, scientific progress, 1 91, 92, 93, 94, 95, 96, 97, 100-101, Animal Welfare Act, 26, 159-160, 162 Anorexia, 59. See also Inappetance 102-103, 152 overview, 79-85 Anticipation or threats of pain, 14 preemptive, 44, 85, 95-97 Anticonvulsants/antiepileptics, 40, 77, 78, reversal of drugs, 91 79, 85, 97, 152 side effects, 51, 77, 80-81, 82, 96, 104, Antidepressants, 77, 97 105 Antiretroviral drugs, 152 species/strain differences in response, 24, Anxiety/fear 73 behavioral interventions, 42-43 synergy, 77, 85 disorders, 41 tolerance, dependence, and withdrawal, management, 21 26, 97, 102 modulation of pain, 21, 42-43, 44, 53, tramadol, 77, 78, 81-82, 89, 93, 94, 97 75 unconventional, 85 Anxiolytic drugs, xi, 3, 21, 42, 43, 72, 73, Anatomy and physiology of pain. See 75-76, 79, 85, 106. See also Sedation also Brain; Mechanism of pain; Aspirin, 20 Nociceptors; Neurotransmitters Assessment of pain species differences, 22 behavioral changes, 3, 43, 47-48, 49, Angina, 39 50, 51-63 Animal models of pain biological markers of nociceptor animal welfare considerations, 98-99 activation, 43, 56 burn, 145 brain activity imaging, 43, 56 cancer, 145, 152-153, 154 case-by-case approach, 26 chronic pain, 143, 152 challenges, 14, 17-18 head, 145 clinical parameters, 3, 49-50, 56-63 inflammation, 56, 97, 143, 144, 145, companion animals, 53-55 146-147, 148-149, 150, 154 confounding effects of drugs, 51 joint inflammation, 144, 146-147 distinguishing between noniception and momentary, 143 pain, 14 muscle, 83, 145, 150 extrapolation from human experience, 3, neuropathic, 83, 144, 150-152, 154 24, 43 opioid research, 101 laboratory rodents, 48, 52-53, 55, 58-59 orofacial, 145, 149-150 nociceptive response measurement, persistent pain, 16, 41-42, 98-99, 55-56 144-154 observation techniques, 48, 52, 53, 57

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13 INDEX placebo-controlled studies, 54-55 Bone cancer, 97, 145, 153 protocol, 48, 49 Brain proxy measures of, 17-18 activity imaging, 37, 56 recommendations, 63-64 anterior cingulate, 22, 37 scoring/grading schemes, 48, 49, 50, 52, cerebral cortex, 33, 105 53-54, 55-56, 60, 102 decerebrate model, 19, 23, 34, 37, 38 species-specific clinical signs, 56-63 decorticate preparation, 34, 38 strain differences, 53, 55-56 forebrain regions involved in pain, 22 subjectivity in, 50, 54 limbic emotional circuits, 36 team approach, 48 neurotoxicity of anesthetics and training/experience of staff, 52 analgesics, 86-87 tools, 3, 53-55, 148 structural effects of chronic pain, 15, 23, Association for the Assessment and 41 Accreditation of Laboratory Animal thalamus, 38 Care, 163, 164 Buprenorphine, 51, 52, 55, 78, 80-81, 89, Autonomic responses to noxious stimuli, 93, 94, 96, 103 19, 74 Butorphanol, 75, 78, 80, 100, 101-102, 103 Aversiveness, 11, 14-15, 17, 18, 24-25, 27, Butyrophenones, 75, 76, 85 62, 82, 91, 92, 100 Avoidance responses, 19, 20-21, 23, 63 C Awareness of pain, 18, 20 c-fos, 56 Canadian Council for Animal Care (CCAC), B 120 Back pain, 58, 152 Cancer pain Barbiturates, 74, 75, 76, 86 humane endpoints, 119, 122, 130, 133, Behavior. See also indiidual behaiors 134 analgesic effects, 51, 54, 80-81 management, 15, 85, 88, 89, 97, 99, assessment of changes, 3, 43, 47-48, 49, 105, 152 50, 51-63 models, 145, 152-153, 154 consequences of unrelieved pain, 8, 12- Canine distemper, 129 13, 44, 97-98 Capacity to experience pain, 2, 20-23, 27 interventions for fear/anxiety, 42-43 Capsaicin, 13, 35, 144, 146 nociceptive responses, 19, 35, 100 Cardioprotective drugs, 87-88 operant tests, xii, 20, 21, 35 Cardiothoracic pain, examples of causes, 25 pain responses, 21, 35, 150 Carprofen, 52, 102, 103 pseudaffective reflex, 37-38 Castration, 25, 60, 61 signs of pain, 3, 14, 48, 50, 148, 149- Cats 150, 153 assessment of pain in, 53-54 Benzodiazepines, 75, 76, 85, 86 management of pain, 72, 81, 82, 83, 84, Betamethasone, 104 85, 91, 82, 101 Biological markers of nociceptor activation, signs of pain, 19, 58 43, 56 Cattle, 59, 60-61, 103-104, 105 Birds and poultry Causes of pain in research animals anatomy and physiology of pain behavioral experiments, 26 structures, 22 definition of painful procedure, 24 clinical signs of pain, 62 examples by anatomic location, 3, 24-25 exclusion from Animal Welfare Act, 159 husbandry or veterinary treatment, 25, management of pain, 24, 81, 83, 27 102-104 non-research-related, 25 pain response, 20 pain research, 26, 27

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14 INDEX research byproduct, 26, 27 Definitions and descriptions Central nervous system. See also Brain affect, 18 depressant effects of morphine, 97 awareness, 18 mechanisms of pain, 36-37 consciousness, 18 Central sensitization, xi, 39, 40, 41-42, 43, duration of pain, 16 83, 84, 94, 95 emotion, 18 Chain dogfish (Scyliorhinus retifer), 100 noxious stimuli and nociception, 13-14 Character of pain, 15, 143 pain in humans, 1, 13 Charge to the committee, 7-8 Dehorning, 25, 60, 61 Chemotherapy-induced neuropathy, 151 Depression, 15, 18, 21, 23, 26, 60, 70, Chronic pain 136 animal models, 152 Dermatologic pain, 13, 24, 25, 38, 39 causes, 15, 94, 95 Detomidine, 84 clinical signs, 58, 62 Dexamethasone, 104 context for, 16, 97 Dexmedetomidine, 87 defined, xii, 16 Diabetic neuropathy, 151 deleterious effects, 15, 23 Diazepam, 85 human endpoints, 131, 134, 135, 162, Discrimination of painful states, 20, 21 163 Distress in humans, 16 addressed separately from pain, 1 lifespan considerations, 16 chronic pain and, 15 management, 15, 77, 81, 82-83, 85, 89, signs of, 57 90, 94, 95, 96, 97, 102, 103, 104- Dogs 105, 106 assessment of pain in, 53-54 models, 143, 152 joint inflammation model, 146-147 pathological changes, 15 management of pain in, 71, 72, 81-82, Clinical signs of pain 83, 84, 85, 91, 92, 101, 103 assessment, 3, 49-50, 56-63 nociceptive responses, 19 reliability, 49-50 signs of pain, 48, 57-58 species-specific, 56-63 Droperidol, 75 Duration of pain. See also Chronic pain; Clinical veterinary principles, pain management, 72-73 Momentary pain; Persistent pain Clonidine, 20 Dyspepsia, 148 Cognitive changes, 15 Cold, stimulus response to, 35, 151, 152 E Comfort-improving strategies, 90 Common carp (Cyprinus carpio), 63, 100, Electric shock, 16, 20, 21, 42, 63 101 Electrostimulation, 89-90 Companion animals. See Cats; Dogs Emotion. See also Affect/affective states Complex regional pain syndrome, 144, 151 valence property, 14-15, 18 Consciousness, 18 Endorphins, 80 Controllability of pain, 15, 17 Endpoints. See Humane endpoints Corticosteroids, 104 Enkephalins, 80 COX-2-inhibitiors, 82, 94, 96, 99 Enterotoxemia, 59 Cryotherapy, 89, 90, 93 Environmental enrichment, 42 Cytochrome P450 2D6 deficiency, 81-82 Ethical issues. See also Humane endpoints; The Three Rs imperatives, 8, 11-13, 122 D justification for pain, 11, 26-27, 71 Decerebrate preparation, 19, 23, 34, 37, 38 placebo-controlled studies, 54-55, 105 Decorticate preparation, 34, 38 European Commission, 125

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1 INDEX European Pharmacopoeia, 129 infectious disease research, 122, Euthanasia 128-129 AVMA guidelines, 37-38, 131, 162 international, 119, 120-121, 123, 124- body condition scores, 131 126, 127 decerebrate preparations, 38 model for development of, 135-136 defined, 130 national, 120, 123, 162 methods, 131, 162 OECD, 119, 120-121, 123, 126, 127 nociceptor response measurement after, OLAW, 120, 123, 162 56 scoring sheet, 134 research needs, 131 toxicology studies, 120-121, 122, 125, team approach, 131 126-127 vaccine safety and potency testing, 122, 123, 129-130 F Guinea pigs, 48, 49, 59, 74, 105, 126, 129 Fear. See Anxiety/fear Fentanyl, 74, 75, 78, 80, 89, 93, 103 H Fetal alcohol syndrome, 86 Fish Haloperidol, 75, 85 analgesia, 100-101 Hamsters, 59 anatomy and physiology of pain Head pain, 57, 58, 145 structures, 22, 62 Health and Environmental Sciences Institute, clinical signs of pain, 62-63 128 pain responses, 20-21 Health Research Extension Act, 161 Flunixin, 103-104 Heat Fluphenazine, 85 stimulus response to, 35, 103, 146, 147, 149, 151 therapy, 89, 90 G HIV, 152 Horses, 50, 60, 61, 71-72, 81, 82-83, 84, GABA agonists. 86 92, 103-104 Gabapentin, 77, 79, 85, 93 Humane endpoints. See also Guidance on General anesthesia, 19, 37, 38, 73-75, 88, humane endpoints 91, 96 bioterrorism threats and, 128 Generalized thermal hypoalgesia, 41 chronic pain, 131, 134, 135, 162, 163 Gerbils, 59 clinical signs as, 120, 129 Glia, 40, 94, 95 defined, 120-121 Glutamate, 40 early termnation of study, 120, 126, 127, Goats. See Sheep and goats 130, 131 Green iguanas, 101-102 eliminating death as an endpoint, 128- Grooming changes, 50, 57, 58, 59, 61, 134, 129, 130, 135 149-150 euthanasia, 121, 123, 126-127, 130-131, Guarding painful areas, 50, 51, 57, 150, 135 154 oversight and monitoring, 124 Guidance on humane endpoints. See also pain research, 130 US legal requirements and guidelines pilot studies, 3, 4, 119, 121-122, 124, cancer research, 119, 122, 130, 133, 132 134 policy development by scientific CCAC, 120 community, 122-123 committee support for, 99 recommendations, 4, 131-132 conferences and symposia, 122 regulations, 123, 124-126, 129 ILAR, 122

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16 INDEX strategies to minimize negative impacts, Inappetance, xii, 50, 57, 58, 59, 60, 62, 124, 125, 126 63, 94 team approach to, 132 Infectious disease research, 88, 119, 122, training/experience of staff, 122, 124 128-129 and validity of experiments, 8, 11, 73, Inflammatory bowel syndrome, 148-149 99, 124, 129 Inflammatory pain Humans hyperalgesia and, 3, 39, 41 anatomy and physiology of pain management, 71, 82, 83, 87, 88, 89, 90, structures, 22 93, 94, 97, 101, 104, 152 assessment of pain in, 3, 24, 43, 47, 56 models, 56, 97, 143, 144, 145, 146-147, chronic pain, 16 148-149, 150, 154 definition of pain in, 1, 13 nociceptor response, 35, 56 extrapolation to animals, 3, 24, 43 sickness syndrome, 94 fetal response, 19 Institute for Laboratory Animal Research neonatal injury, 41 (ILAR), 1, 7, 122, 163 nociceptive responses, 14, 19, 23 Institutional animal care and use physiological and behavioral responses, committees, 2, 3, 4, 7, 8, 9, 16, 58, 23, 37 71, 73, 98, 120, 123, 124, 130, 132, studies of pain in, 55 135, 136, 159, 160, 161, 162, 163, Hydromorphone, 78, 80 164-165 Intensity of pain, 15. See also Threshold for Hyperalgesia cancer pain, 153 pain; Tolerance of pain defined, xii, 36, 39 and dosage, 78, 102 detection, 55 and regulations and legislation, 15-16 inflammatory pain and, 3, 38, 39, Interferential therapy, 89 146 International Association for the Study of joint inflammation, 147 Pain, 1, 13, 17 management/prevention, 39, 84, 89-90, International Life Sciences Institute, 126 94, 95, 96 International regulations and guidelines for mediators, 39 safety assessment, 119, 120-121, muscle pain, 150 123, 124-126, 127 neuropathic pain, 151 Interstitial cystitis, 148-149 nociceptor excitability and, 36, 39, 55, Intervertebral disk disease, 90 56, 95 Invertebrates, capacity to experience pain, orofacial pain models, 150 22 postoperative pain, 149 Irritable bowel syndrome, 148-149 primary, 39, 149 Isoflurane, 19, 53, 74, 86-87, 91, 101-102, secondary, 39, 149, 150 104 sickness syndrome and, 26 thermal, 151, 152 J untreated neonatal pain and, 41-42 visceral pain, 149 Joint pain, 14, 39, 144, 146-147 Hypertension, 15, 19 Hypnorm®, 75 K I Ketamine, 40, 75, 76, 77, 79, 84, 86, 87, 88, 89, 93, 84, 96 Ice, 91, 92 Ketoprofen, 52, 100, 101, 102, 103-104 Immune suppression/dysfunction, 3, 13, 15, 44, 66-69, 80, 88-89, 97

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1 INDEX L guidelines and protocols, 73, 160-164 hyperalgesia, 39, 84, 89-90, 94, 95, 96 Laboratory rodents. See also indiidual ice, 92 species immunosuppression and reduction of assessment of pain in, 48, 52-53, 55, inflammatory response, 66-69 58-59 legal requirements, 8, 26, 71, 159-161 pica, 80 limitations of available information, preemptive analgesia, 95-96 104-105 Leptospira pomona bacterin, 129 molecular targets for, 35, 40 Licking, 19, 50, 58, 59, 61, 146 momentary non-tissue-damaging pain, 3, Lidocaine, 77, 79, 91, 92 15, 82, 83, 91-93, 106 Local anesthetics, xi, 60, 72, 73, 76, 77, 78, multimodal regimens, 72, 74-75, 77, 78, 79, 83, 89, 91-92, 93, 96, 97, 101, 81, 82-83, 84, 87, 94, 96 106, 126, 127 neuroleptanalgesia, 75-76, 91 Location of pain, 15. See also Dermatologic neuropathic pain, 84, 85, 97, 98-99, 152 pain; Joint pain; Musculoskeletal neuroprotective drugs, 87 pain; Visceral/adbdominal pain neurotoxicity of drugs, 86-87 Locomotor activity, 19, 50, 51, 53, 57, 86 nonmammalian species, 24, 81, 83, Love Canal, 125 99-104 nonpharmacologic methods, 3, 78, 89- 90, 91, 92, 95, 97 M physical distraction and training, 92-93 postprocedural and postsurgical pain, Mammals, capacity to experience pain, 38-39, 44, 54-55, 72, 77, 78, 82, 84, 20-23 85, 93-94, 98-99, 100, 104-105, 106 Management and prevention of pain. See practical applications and also Analgesics and anesthetics; considerations, 44, 91-99 Anxiolytic drugs; Sedation; indiidual recommendations, 106 species sickness syndrome, 94-95 animal welfare considerations in strategies for laboratory animals, 73-79 persistent pain models, 42, 98-99 training/experience of staff, 73 behavioral interventions to reduce visceral, 82, 83, 84, 79, 97, 104 anxiety, 42-43 Manual therapy, 89, 90 cancer, 15, 85, 88, 89, 97, 99, 105, 152 Marek’s disease, 129 cardioprotective drugs, 87-88 Mechanism of pain case-by-case approach, 26 central nervous system, 13, 14, 19, chronic pain, 15, 77, 81, 82-83, 85, 89, 36-37 90, 94, 95, 96, 97, 102, 103, 104- modulatory influences, 15, 42-43, 44 105, 106 nociception, 13, 19, 33-38, 100 clinical veterinary guidelines, 72-73 nociceptors, 13, 35-36 comfort-improving strategies, 42, 90, 97 nonmammalian species, 101, 105 confounding and beneficial effects of ontogeny, 40-42, 44 drugs, 73, 85-89 persistent pain, 38-40, 44 consequences of unrelieved pain, 8, 12- recommendations, 43-44 13, 44, 97-98 tissue differences in activation of drugs, 3, 39, 40, 79-90; see also specific nociceptors, 13-14 classes of drugs and indiidual drugs Medetomidine, 84, 87, 96 environmental enrichment, 42 Meloxicam, 52, 102, 104 ethical and moral imperative, 2, 44 Memantine, 84, 87 focus of, 15 Methadone, 78 gate control theory, 92

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18 INDEX Methylprednisone, 104 management, 84, 85, 97, 98-99, 152 Mice models, 83, 144, 150-152, 154 assessment of pain in, 51, 52-53 response, 21, 39 drug effects on behavior, 51 Neuroprotective drugs, 87 environmental enrichment, 42 Neurotoxicity, 86-87 exclusion from Animal Welfare Act, 159 Neurotransmitters, 22, 40, 74 management of pain in, 73, 81, 82, 83, Nitrous oxide, 76, 86-87 84, 97, 98, 105 NMDA receptor antagonists, 76, 77, 78, 84, pain response, 20 86, 87, 94, 95, 96, 97 persistent pain models, 143, 147, 148, Nociception 151, 153, 154 absence of pain and, 33 safety assessment in, 126, 129 anatomical distribution, 34, 43 signs of pain, 48, 58-59 behavioral responses, 19, 35, 100 Midazolam, 75, 86 biological markers of activation, 43, 56 Momentary pain defined, xii, 33 anatomical basis, 35 early postnatal injury and, 25 n.3 assessment, 58, 102 measuring response, 55-56 defined, xii, 16, 165 modulators, 81, 84, 92 examples of sources, 91 pain distinguished from, 1, 14, 18, 19, management, 3, 15, 82, 83, 91-93, 106 20-21, 33-38, 43 measurement of nociceptive responses, strain differences in response, 55-56 55 tissue differences in activation, 13-14 models of, 143 unconscious responses, 19 multiple episodes, 106 withdrawal reflexes, 14, 16, 35, 36, 55, responses to, 17, 143 74 Morphine, xi, 41, 63, 78, 80, 89, 93, 95, Nociceptors 97, 100-101, 103 activation, 13, 33, 56 Multiple sclerosis, 151 defined, 35 Musculoskeletal pain in fish, 63-64, 100 examples of causes, 25 myelinated A-delta fiber population, 35- management, 89-90 36, 40 models, 83, 145, 150 sensitization, xii, 36, 39, 95 noxious stimuli, 14 sleeping or silent, 36, 95 Mutilation, 50, 57, 136 spontaneous activity in, 36 unmyelinated C-fiber population, 35, 40 N Nonhuman primates, 12, 20, 49, 50, 57, 82, 86, 91, 105 Naloxone, 63 Norepinephrine, 81 National Institutes of Health Northern grass frog (Rana pipiens), 101 data sharing with EPA, 125 NSAIDs, 20, 39, 51, 52, 76, 77, 78, 79, Office of Laboratory Animal Welfare 82-83, 93, 94, 96, 97, 99, 100, 101, (OLAW), 120, 123, 162 102, 103, 104, 152 National Research Council Guide for the Care and Use of Laboratory Animals, 163-164 O Neonatal pain, 41-42, 44 Neuroleptic drugs, 75, 76 Observation techniques, 48, 52, 53, 57 Neuromuscular blocking agents, 74 Ocular pain, 25, 126-127 Neuropathic pain Ontogeny of pain, 40-42 in cancer, 153 Operant response experiments, xii, 20, 21, examples of causes, 25 35

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1 INDEX Opioids, xi, 24, 41, 51, 52, 54, 63, 72, 75, Phenothiazines, 75, 76, 85 76, 77, 78, 79, 80-81, 84, 88, 89, Phenylbutazone, 104 91, 92, 93, 94, 95, 96, 97, 100-101, Physical distraction and training, 92-93 Physiological response to pain, 14. See also 102-103, 152 Organisation for Economic Co-operation Anatomy and physiology; Clinical and Development (OECD), 119, 120- signs of pain 121, 123, 126, 127 Pigeons, 20, 21, 104 Orofacial pain Pigs, 21, 61-62, 74, 91, 98, 105 examples of causes, 25 Pilot studies, 3, 4, 119, 121-122, 124, 132 models, 145, 149-150 Postherpetic neuralgia, 85, 144, 151 Osteoarthritis, 15, 16, 20, 21, 25, 53, 90, Postprocedural and postsurgical pain 102, 103-105, 144 assessment, 39, 48, 51, 52-53, 55 Oxymorphone, 75 behavioral and physiological effects, 23, 51 ethical issues in placebo-controlled P studies, 54-55 defined, xii, 16 Pain, generally development of, 38-40 affective component, 36 intensity, 93 anatomical distribution, 34 limitations of information, 104-105 behavioral responses, 21, 35 management, 38-39, 44, 54-55, 72, 77, behavioral signs, 3, 14, 48, 50 78, 82, 84, 85, 93-94, 98-99, 100, capacity to experience, 2, 20-23, 27 104-105, 106 causes of pain, 3, 24-25, 26, 29 models, 98-99, 145, 149 defined, xii, 33 nociceptive responses, 19 distress addressed separately, 1 protective premedication, 44, 85, 95-97 ethical justification for pain, 26-27 protective role of pain, 23 n.2 magnitude, 34 sickness syndrome, 25, 26, 38, 94-95 modulators, 21, 42-43, 44, 53, 75 Poultry. See Birds and poultry nociception distinguished from, 1, 14, Pregabalin, 85 18, 19, 20-21, 33-38, 43 Primates. See Nonhuman primates and pain management, 3, 38 Principles and standards of care perception in nonmammalian species, clinical veterinary, 72-73 100 Three Rs, 3, 12-13, 78, 120, 122 protective role, 76 Propofol, 74, 76, 88, 91 unrelieved, 8, 12-13, 44, 97-98 Prostaglandins, 82 Pain research. See also Animal models of Pseudaffective reflex, 37-38 pain Psychological factors, 3, 15 humane endpoints, 130 Public Health Service Policy on Humane Painful bladder syndrome, 148-149 Care and Use of Laboratory Animals, Pancreatic inflammation, 149, 153 26, 161-162, 163 Persistent pain. See also Chronic pain; Postprocedural and postsurgical pain animal models, 1154 q animal welfare considerations in animal models of, 98-99 Qualia, 18 Qualitative properties of pain. See defined, xii, 16 deleterious effects, 23, 41-42 Character of pain; Duration of pain; development, 38-40, 44 Intensity of pain; Location of pain management, 98-99 Quantitative Structure-Activity Relationship, signs of, 60 125 Phantom limb pain, 95

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180 INDEX R S Rabbits, 48, 49, 53, 59, 72, 74, 98, 105, Safety assessment. See also Toxicology; 147, 152 Vaccine Rainbow trout (Oncorhynchus mykiss), 63, alternatives to animal use, 125 100 international regulations and guidelines, Rats 124-126 assessment of pain in, 52, 55 Salicylate, 104 Sea slug (Aplysia), 19 drug doses, 55 exclusion from Animal Welfare Act, Sedation, 26, 51, 53, 72, 75-76, 77, 83, 84, 91, 92, 97, 103, 162, 163. See also 159 management of pain in, 73, 80, 81, 82, Anxiolytic drugs 83, 84, 85, 87, 96, 97, 98, 105 Serotonin, 81 muscle pain models, 150 Sevoflurane, 53, 91 neonatal pain, 41-42, 44 Sheep and goats, 50, 59, 60, 61, 81, 105 nociceptive responses, 19, 55 Sickness syndrome, 25, 26, 38, 94-95 Skin. See Dermatologic orofacial pain models, 150 pain responses, 20, 21, 23 Sleep disruption, 21, 23 persistent pain models, 146, 147, 148, Soft tissue models of pain, 83 149-150, 151, 153, 154 Species differences porphyrin secretion (red tears), 58-59 anatomy and physiology of pain, 22 signs of pain, 48, 58-59 capability of experiencing pain, 2, 20-23 stress-induced analgesia, 42 drug response, 24, 73 visceral pain models, 52, 82, 145, 148, Spinal cord transection, 14, 33, 34, 38 149 Spino-bulbo-spinal reflex, 37 REACH (Registration, Evaluation, and Spontaneous pain, 98-99, 151, 153-154 Authorization of Chemicals), 125 Statement of task, 2 Recognition of pain. See Behavior; Clinical Stress signs of pain behavioral interventions, 42 Recommendations disorders, 41 assessment of pain, 43-44 endocrine response to castration, 60 education of investigators, veterinarians, gate control theory, 92 and animal care staff, 5 modulation of pain, 42-43 experience of pain, 27 Stress-induced analgesia, 42, 43 funding for pain-related studies, 4 Substance P, 40 humane endpoints, 4, 131-132 Sweating, 50, 60 management of pain, 4, 106 Sympathetic responses, 19, 154 nonmammalian species, 4 Systemic pain, examples of causes, 25 The Three Rs, 27 US Government Principle #4, 4, 27 T Red-eared slider, 101 Referred pain, 39, 149 Tail docking, 25, 60, 61 Regulatory requirements, 8, 71, 123, 124- Taxol, 152 126, 129, 159-161 Temporomandibular joint pain, 149 Reptiles, 2, 20, 21, 22, 62, 81, 101-102 Tetanus antitoxin, 129 Respiration rate, 49-50, 57, 59, 60-61, 62, Thalidomide, 124 80, 96, 98, 100, 101, 131, 136 The Three Rs, 3, 12-13, 27, 122 Rheumatoid arthritis, 90, 149 Thiopental, 88 Rodents. See Laboratory rodents; indiidual Thoracic pain, 25, 58, 60 species Threshold for pain, 15, 39

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181 INDEX Tiletamine-zolazepam (Telazol®), 75, 76 Public Health Service Policy on Humane Tissue differences Care and Use of Laboratory Animals, in activation of nociceptors, 13-14 26, 161-162, 163 in response to pain, 24 refinement principle, 12 Tolerance of pain, 15 US Government Principles for the Tonic pain. See Persistent pain Utilization and Care of Vertebrate Toxicology studies, 88, 120-121, 122, 125, Animals Used in Testing, Research, 126-127 and Training, 4, 24, 27, 99, 130-131, Training/experience of personnel, 8, 42, 48, 162-163 52, 73, 122, 124 USDA policies, 20, 26, 129, 160-161 Tramadol, 77, 78, 81-82, 89, 93, 94, 97 Uterine inflammation, 149 Tribromoethanol, 74, 76 TRPM8, 35 V TRPV1, 35, 146 Vaccine safety and potency testing, 122, 123, 129-130 U Vincristine, 152 Ungulates, 59-62. See also indiidual Visceral/abdominal pain species clinical signs, 48, 57, 58, 60, 61 United Kingdom Coordinating Committee examples of causes, 25 on Cancer Research, 130 management, 82, 83, 84, 79, 97, 104 Urethane, 74, 76 models, 52, 82, 144-145, 148-149, 154 Urogenital pain, 25 neonatal, 41 US Department of Agriculture, 20, 26, 129, noxious stimuli, 14 160-161 referred pain, 39 US Environmental Protection Agency, 125, Vocalization, 16, 19, 21, 37, 50, 57, 58, 59, 126 60, 61-62, 136, 147, 153 US Food and Drug Administration, 129 US Government Principles for the W Utilization and Care of Vertebrate Animals Used in Testing, Research, Withdrawal reflexes, 14, 16, 35, 36, 74, 146 and Training, 4, 24, 27, 99, 130-131, World Health Organization, 129 162-163 US legal requirements and guidelines American College of Laboratory Animal X Medicine, 164-165 Animal Welfare Act, 26, 159-160, Xenon, 87 164-165 Xenopus sp., 101 Association for the Assessment and Xylazine, 84 Accreditation of Laboratory Animal Care International, 163, 164 Health Research Extension Act, 161 Z intensity of pain and, 15-16 Zebrafish (Danio rerio), 100 justifiable pain, 26 Zuclopenthixol, 85 National Research Council Guide for the Care and Use of Laboratory Animals, 163-164

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