Recognition and Alleviation of Pain in Laboratory Animals (2009) / Chapter Skim
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4 Effective Pain Management
4 Effective Pain Management
Pages 71-118
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From page 71... ...
While certain conditions reliably cause severe pain (e.g., acute nerve compression, burns, spastic contraction of smooth muscle) and inflammation often contributes to the worsening of pain, scientists do not fully understand how much pain to expect in various animal species.
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From page 72... ...
. • Use of more than one type of management strategy (e.g., multimodal anal gesia [targeting multiple pain mechanisms with the use of local anesthetics and opioids]
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From page 73... ...
• Researchers, veterinarians, and animal care professionals should be respon sible for learning about the assessment, prevention, and management of pain in laboratory animals. • Veterinarians and animal care professionals should develop IACUC-approved educational guidelines and protocols for the management of pain in laboratory animals at their institution.
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From page 74... ...
During anesthesia not accompanied by neuromuscular blocking agents, depression of somatic reflex responses is the most widely used method for ensuring an appropriate depth of anesthesia. In all animal species, absence of the pedal withdrawal reflex indicates a surgical plane of anesthesia (i.e., anesthesia that is deep enough to eliminate the experience of pain and thus allow surgery to take place)
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From page 75... ...
Readers are referred to the section "Modulatory Influences on Pain: Anxiety, Fear, and Stress" in Chapter 2 for a discussion of the relationship of anxiety and pain. Neuroleptanalgesia is an intense analgesic and amnesic state produced by the combination of an opioid analgesic and a neuroleptic drug (this description is adapted from the American Heritage Medical Dictionary 2007)
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From page 76... ...
ing tranquilizers, sedatives, and anesthetics, commonly used in laboratory animals. Analgesia Conventional analgesic drug classes include opioids, NSAIDs, and local anesthetics.
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From page 77... ...
Advanced Analgesic Techniques The ability to provide analgesia to laboratory animals is limited by the lack of information about species-specific drug effects and doses. It is perhaps useful to understand the state-of-the-art techniques currently used in clinical (i.e., nonlaboratory)
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From page 78... ...
, tramadol, α2-agonists, NMDA antagonists High Multimodal analgesia recommended mu-opioid agonists (morphine, hydromorphone, fentanyl, methadone) + one or more of the following: NSAIDs, local anesthetics, α2-agonists, antiepileptic drugs, NMDA antagonists Advanced analgesic techniques: epidural administration of local anesthetics with or without opioids and constant rate infusions Nonpharmacologic Methods Nonpharmacologic approaches to pain management are appropriate when the use of pharmacological methods is contraindicated, when effective analgesic drugs are not available, or to complement drug therapy.
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From page 79... ...
Epidural administration of drugs has not been studied in nonmammalian vertebrates. • Local anesthetics can be injected into joints, wounds, and body cavities (ab dominal or pleural)
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From page 80... ...
. Instead, this section provides an overview of analgesic drugs that are currently used or may become useful in laboratory animal medicine.
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From page 81... ...
Additionally, long-duration formulations of opioids have been investigated in animal models and, although not yet commercially available, may represent a future method to provide sustained analgesia in laboratory animals (Krugner-Higby et al. 2008; Smith et al.
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From page 82... ...
In animals for which therapeutic dose ranges have been determined, NSAIDs can be used as relatively long-acting (12-24 hour) agents for momentary, procedural, and persistent or chronic pain.
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From page 83... ...
; by decreasing sensory input, local anesthetics inhibit peripheral and central sensitization (White 2005)
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From page 84... ...
High doses in combination with another anesthetic drug (e.g., xylazine) are commonly used to anesthetize a variety of laboratory animals (particularly rodents)
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From page 85... ...
. High doses of α2-adrenoreceptor agonists used as presurgical sedatives or in anesthetic regimes may confer a degree of perioperative analgesia in laboratory animals, but this remains to be demonstrated.
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From page 86... ...
The neurotoxic effect of CNS depressants on the developing brain was heralded by the Olney group, which reported accelerated neurodegeneration in rat pups exposed to NMDA receptor antagonists, γ-aminobutyric acid (GABA) agonists, and anticonvulsant drugs (Bittigau et al.
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From page 87... ...
Neuroprotection Anesthetic drugs have been shown to impart neuroprotective effects as well. In contrast to the neurotoxic effect of NMDA receptor antagonists described above, ketamine and memantine also protect neurons from excitotoxic injury.
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From page 88... ...
Inflammation is part of the immune response, a "first responder" that protects the animal from invading organisms or insults and modulates cellular and homeostatic events. Most, if not all, modern anesthetic agents can alter certain inflammatory markers of immune function in in vitro and in vivo models both in humans and in animal models (Galley et al.
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From page 89... ...
and on the relationship between the dose and the amount of pain. Other analgesics (e.g., local anesthetics, ketamine)
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From page 90... ...
methods has not yet been proven for laboratory animals. Manual modalities include joint manipulation/mobilization and massage.
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From page 91... ...
Topical application of local anesthetic preparations or a short, 1- to 2-minute application of ice or vapocoolant spray to the site may greatly reduce the pain of injection or other superficial pain-producing procedures; studies in cats and humans show reduced pain during minor procedures following topical application of local anesthetics (Gibbon et al. 2003; Howard 2005; Luhmann et al.
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From page 92... ...
. Although the usefulness of ice application has not been studied in laboratory animals, it should be considered a helpful method for the alleviation of brief pain in laboratory animals.
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From page 93... ...
. However, the amount of pressure applied can make the difference between a pain-reducing and a pain-producing stimulus; a useful guideline for large laboratory animals is that pressure not exceed that which the handler could apply comfortably to his or her own body.
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From page 94... ...
. Because many laboratory animal models include some degree of strong immune stimulation associated with the above conditions, it is important to appreciate that sick animals may be more sensitive to external noxious and nonnoxious stimuli.
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From page 95... ...
However, because central sensitization is associated with multiple molecular, structural, and neurophysiological changes in CNS neurons and glia, it may also be maladaptive if these changes persist beyond the period of expected postoperative pain (perhaps becoming independent of the original injury) or contribute to the development of a chronic pain state (Romero-Sandoval et al.
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From page 96... ...
. NSAIDs and local anesthetics do not generally interfere with opioid-induced CNS depression or the action of other anesthetics, but NSAIDs may take 30 or more minutes to be effective whereas local anesthetics act rapidly.
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From page 97... ...
. Drug classes commonly used to manage chronic pain include NSAIDs, opioids, tramadol, antiepileptics, antidepressants, and, to a lesser extent, NMDA receptor antagonists and local anesthetics.
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From page 98... ...
Animal Welfare Considerations of Research with Persistent Pain Models Research on pain as a study subject is described in Appendix A Because of the painful nature of these models and the underlying assumption that analgesics may interfere with the research outcomes, it is important to consider the following questions: • Is it possible to objectively assess discomfort and/or spontaneous pain or recognize the differences between these and the implica tions for animal welfare?
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From page 99... ...
, and most species' spontaneous pain-related behaviors have not been studied. Moreover, the question arises whether to treat what appears to be spontaneous pain in such models, as central nervous system and invasive cancer pain models typically increase in pain intensity and are irreversible.
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From page 100... ...
also had no effect in the dogfish; however, both ketoprofen and butorphanol were given via immersion, and drug uptake through the gills may not have occurred since morphine uptake via this route of administra 3 The doses of analgesic drugs discussed in the text are for investigational not clinical use unless otherwise indicated.
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From page 101... ...
. The most commonly used drugs were opioids, NSAIDs, and local anesthetics.
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From page 102... ...
is probably not representative of either postsurgical or chronic pain, so it is important to recognize that the dose and duration information that they convey may differ (i.e., the dose may be higher or lower than needed) in the context of clinical pain in birds.
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From page 103... ...
2007) indicate that opioids acting at the mu-opioid receptor are either not effective in birds or are much less so than in mammals, whereas butorphanol, a kappa agonist opioid with antagonist efficacy at the mu-opioid receptor, is considered the opioid of choice for acute and chronic pain management in birds (Paul-Murphy et al.
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From page 104... ...
As NSAIDs have not been reliably found to reduce the minimal alveolar concentration of inhalant anesthetics in mammalian species, the results of this study must be interpreted cautiously. Neither phenylbutazone nor acetaminophen showed analgesic activity in lame chickens (Hocking et al.
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From page 105... ...
The effective reduction and management of pain in laboratory animals to optimize both their well-being and the quality of the research is still fraught with limitations. However, extrapolation of techniques from other species, accounting for differences in physiology between them, and attention to the vast scientific literature that uses animal models can improve the ability to manage pain in animals in the laboratory.
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From page 106... ...
2. The amount of pain experienced by laboratory animals can be reduced through the use of preventive or therapeutic strategies or their combination.
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From page 107... ...
2005. Antiepileptics and the treatment of neuropathic pain: Evidence from animal models.
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From page 108... ...
2007. The clinical role of NMDA receptor antagonists for the treatment of postoperative pain.
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From page 109... ...
In: Fish R, Brown M, Danneman P, Karas A, eds. Anesthesia and Analgesia in Laboratory Animals.
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From page 110... ...
2005. Formulary for laboratory animals.
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From page 111... ...
2001. Diminished body weight and activity patterns in mice following surgery: Implications for control of post-procedural pain/dis tress in laboratory animals.
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From page 112... ...
1990. The assessment and control of the severity of scientific procedures on laboratory animals.
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From page 113... ...
1999. Systematic review and meta-analysis of randomized controlled trials of cognitive behaviour therapy and behaviour therapy for chronic pain in adults, excluding headache.
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From page 114... ...
2000. Chronic pain as an outcome of surgery: A review of predictive factors.
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From page 115... ...
2007. Preventing the development of chronic pain after ortho paedic surgery with preventive multimodal analgesic techniques.
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From page 116... ...
2006. Difficult pain syndromes: Bone pain, visceral pain, and neuropathic pain.
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From page 117... ...
2004. Opioid research in amphibians: An alternative pain model yielding insights on the evolution of opioid receptors.
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From page 118... ...
2005. The changing role of non-opioid analgesic techniques in the management of postoperative pain.
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