Recognition and Alleviation of Pain and Distress in Laboratory Animals (1992) / Chapter Skim
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5 Control of Pain
5 Control of Pain
Pages 53-84
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From page 53... ...
It discusses the pharmacology of general anesthesia in laboratory animals and describes the major classes of drugs used to achieve the clinical goals of analgesia, sedation, and restraint (see Table 5-14. Discussion of the major drug classes is organized for the reader to extract information along three dimensions-clinical use, pharmacologic effects, and dose recommendations each related to particular species.
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From page 54... ...
The anesthetic state can be monitored by assessing papillary size, palpebral and toepinch response, stability of heart rate and blood pressure, and electroencephalographic activity. In a study in which anesthetic agents would confound the data, surgical lesions of the central nervous system can be made under anesthesia, the animal allowed to recover from anesthesia, and data collected on a functional decerebrate with no possibility of conscious sensation.
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From page 55... ...
Such stress is minimized by the use of unrestrained escape-avoidance tasks, in which animals are taught to control the stimulus. The teaching uses operant-conditioning procedures and closely mimics conditions under which humans participate in experimental pain studies: animals choose to participate by initiating trials (e.g., to obtain food)
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From page 56... ...
· What is the clinical goal of drug administration? Common clinical goals include general anesthesia for surgical procedures, lighter general anesthesia for experimental studies that cannot be conducted in awake animals, sedation and analgesia for minor surgical and diagnostic procedures, management of postsurgical pain and pain associated with disease, sedation and tranquilization for the relief of non-pain-induced stress or distress, and temporary restraint.
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From page 57... ...
The opioid agonists, which include the morphine-like drugs (e.g., fentanyl and oxymorphone) , produce analgesia and sedation through the activation of opioid receptors in the CNS.
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From page 58... ...
Ultimate goals of clinical and investigative anesthesia might differ, but the basic principles of good anesthetic techniques do not: maintain a depth of anesthesia that minimizes changes in physiologic function, blocks response to stimulation, and produces unconsciousness. Inhalationa1t Anesthesia The development of inhalational anesthesia for both companion and laboratory animals has progressed a great deal in the last 20 years.
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From page 59... ...
The selection, measurement, and maintenance of the end-tidal concentration at some multiple of the MAC will allow light anesthesia to be used with neuromuscular blocking agents while ensuring an adequate depth of anesthesia. Under these circumstances, the investigator can be confident that the animal is unconscious.
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From page 60... ...
Intravenous Anesthesia Inhalational anesthesia is often preferred for major surgical procedures, but steady-state anesthesia with some drugs can also can be obtained through intravenous administration. The ideal method to establish a steady-state level of anesthesia is to use pharmacokinetic measurements to calculate loading and infusion rates.
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From page 61... ...
The ultrashort-acting barbiturates are commonly used to induce anesthesia before maintenance with the inhalational anesthetics. The amount necessary is less than that required for surgical intervention; all that is necessary is anesthesia of adequate depth to produce sufficient muscle relaxation for tracheal intubation.
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From page 62... ...
Deep anesthesia abolishes those reflexes. Barbiturates, like other general anesthetics, reduce blood pressure, cardiac output, and renal blood flow, but increase or do not change heart rate.
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From page 63... ...
A dose range of 30-60 mg/kg has been reported for rodents (Wixson et al., 1987a) , but doses as high as 90 mg/kg have also been given (Hughes, 19811.
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From page 64... ...
Nystagmus might occur, and lacrimal secretions persist. An increase in respiration might occur, but death from the high dose necessary for surgical anesthesia is eventually due to respiratory depression (Flecknell, 1987)
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From page 65... ...
The two drugs are combined in a 1:1 ratio, and TABLE 5-4 Dose Ranges of Ketamine Administered Intramuscularly in Primates Dose, Adjunct Drug, Species mg/kg mg/kg Comments References Baboon 10 Diazepam, Light Woofson et al., 1980 7.5 anesthesia Chimpanzee 7-10 None Light Bonner et al., 1972 anesthesia Gorilla 8-10 None Light Bonner et al., 1972 (lowland) anesthesia Rhesus 7 Xylazine Anesthesia (not Reutlinger et al., 1980 recommended)
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From page 66... ...
66 Cal Cal C)
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From page 67... ...
67 o oo _ oo oo C;s _ _ oo .
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From page 68... ...
Cardiorespiratory effects over a dose range of 10-24 mg/kg included transient reductions in blood pressure and aortic blood flow and apnea at higher doses (Hellyer et al., 1988~. In calves, Telazol produced rapid induction, good to excellent muscle relaxation, minimal regurgitation or bloat, and minimal cardiovascular changes over a dose range of 4- 12 mg/kg (tin et al., 1989~.
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From page 69... ...
Dose Recommendations (Table 5-6 J Innovar-Vet is commonly administered intramuscularly, but can be administered intravenously and subcutaneously. The broad dose range among species reflects not only species variation, but the wide margin of safety of neuroleptanalgesia.
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From page 70... ...
When used properly, intravenous agonists are cardiovascular-sparing and produce the least cardiovascular depression of all the anesthetic techniques. Agonists can be used in dogs, nonhuman primates, and, in some cases, horses and cats to control pain.
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From page 71... ...
Agonist-antagonists can partially reverse the analgesic, cardiovascular, and respiratory depressant effects of opioid agonists, such as the opioid component of neuroleptanalgesics (Flecknell et al., 19891. The antagonist naloxone hydrochloride is used to reverse the sedative and depressant effects of the opioids when they have been used for temporary restraint for diagnostic procedures, transport, or minor surgery or when an overdose has been administered.
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From page 72... ...
When agonists are used as preanesthetic sedatives, general anesthetic agents should be administered carefully and in reduced amounts, to prevent respiratory depression. Use of morphine and other opioids alone in farm animals (cow, sheep, goat, and pig)
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From page 73... ...
CONTROL OF PAIN 73 TABLE 5-7 Doses of Opioid Agonists and Opioid Agonist-Antagonists in Various Speciesa Dose, mg/kg Species Drug (Routeb) Reference Cat Oxymorphone 0.2 (iv, im)
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From page 74... ...
In dogs, dose-dependent sedation occurred over a dose range of 0.1-0.4 mg/kg intravenously (Trim, 19831. Buprenorphine, approved for use in the United States in 1989, has been recommended as an analgesic to alleviate moderate to severe pain in several laboratory animal species (Flecknell, 19871.
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From page 75... ...
Antagonists: Naloxone (0.04 mg/l~g intravenously) is as effective in animals as in humans in reversing the analgesic, sedative, cardiovascular, and respiratory effect of opioid agonists.
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From page 76... ...
NSAIDs, with the possible exception of acetaminophen, are potent inhibitors of cyclo-oxygenase (Gilman et al., 1990~. The eicosanoids are synthesized by all cells except red blood cells and have a major effect on cellular functions.
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From page 77... ...
Drugs other than NSAIDs (for example, corticosteroids) can also modify the release of arachidonic acid and can interfere with experimental studies.
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From page 78... ...
with minimal cardiovascular and respiratory depression (Van Citters et al., 19641. However, the depth of analgesia is usually inadequate for surgical procedures (Flecknell, 1987; Holzgrefe et al.
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From page 79... ...
has compiled an extensive review of neuromuscular blocking agents and their use in dogs, cats, pigs, horses, sheep, and calves. This TABLE 5-10 Doses of Pancuronium in Domestic Species Dose, Duration, Species mg/kg minutes Anesthetic Reference Calf 43 + ga 43 + 1ga Halothane-O2 Hildebrand and Howitt, 1984 Sheep 5.0 + 0.61 21 + 2.5 Halothane-O2 Klein et al., 1985; 0.15/min steady state Cass et al., 1980 Horse 82 + 7.3 20-35 Halothane-O2 Klein et al., 1983 Pony 125 + 20a 16 Halothane-O2 Manley et al., 1983 Pig 50 Thiopental- Denny and Lucke, 1977 N2O-O2, or ketamine 10 Lumb and Jones, 1984 Dog 22 + 3 108 + 10 Halothane Booij et al., 1980 Cat 20 15 + 2a Halothane- Hughes and Chapple, 1976 a-chloralose 22 14 + 2 Pentobarbital Durant et al., 1980 34 8.8 + 2.3 a-Chloralose- Durant et al., 1979 pentobarbital aMean + standard deviation.
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From page 80... ...
Because of an animal's inability to respond to stimuli when paralyzed, it is difficult to evaluate whether the animal is anesthetized or can feel pain. Observable signs that might indicate pain under paralysis include autonomic nervous system changes such as lacrimation and salivation, sudden changes in heart rate and arterial blood pressure, and changes in pupil size.
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From page 81... ...
Preferably, a ratemeter sounds an alarm if heart rate is above or below its natural resting range. Indeed, once an immobilized animal has recovered from general anesthesia, the heart rate might provide the experimenter with a ready index of the animal's state; an increase due to a relatively innocuous stimulus provides some assurance that the animal is alert and is not experiencing a severe stress.
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From page 82... ...
But there is very little evidence that would permit a conclusion that cephalopods perceive pain. Attempts of cold-blooded vertebrates and invertebrates to escape or avoid aversive stimuli are not sufficient to conclude that these animals experience the affective and sensory qualities of painful stimuli as do warm-blooded vertebrates, but they do indicate that at least some degree of stress can be accompanied by a negative motivational state, and they should not be ignored.
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From page 83... ...
It is also useful for restraint and as an adjunct to general anesthesia in cold-blooded animals (CCAC, 1980; Phifer and Terry, 1986; Arena and Richardson, 19901. TONIC IMMOBILITY Physical restraint can produce severe stress in some animal species (Gartner et al., 1980; Pare and Glavin, 1986~.
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From page 84... ...
Initially, the heart rate of immobilized animals can increase; at later stages, the rate tends to decrease. Fully immobilized rabbits exhibit pronounced catalepsy with reduced muscle tone.
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