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Recognition and Alleviation of Pain and Distress in Laboratory Animals
Drugs categorized as general anesthetics, sedatives, hypnotics, ataractics, anxiolytics, tranquilizers, nonsteroidal anti-inflammatory drugs, and opioids all have been used to prevent or minimize pain and distress produced by painful and nonpainful procedures and to produce unconsciousness and analgesia for surgical procedures. Barbiturates and inhalational anesthetics are considered general anesthetics and are commonly used as total anesthetic agents, that is, drugs that produce unconsciousness and muscle relaxation sufficient for surgical intervention. Barbiturates are also considered hypnotics and are used in veterinary medicine as general anesthetics.
General anesthetics produce a total loss of awareness and of responsiveness to painful stimuli during surgical procedures. Other drugs are also used to alleviate pain and distress. Neuroleptanalgesics, dissociative anesthetics, and continuously infused potent opioids in people or animals premedicated with low doses of hypnotics or benzodiazepines are used for producing surgical anesthesia. Opioids are used because of their cardiovascular-sparing aspects and lack of profound depression of the central nervous system (CNS); they should therefore be considered for studies involving the CNS and cardiovascular system.
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. The dissociative anesthetic agent ketamine has both analgesic and anesthetic properties, but should be combined with other drugs for major procedures. The anti-inflammatory action of the nonsteroidal anti-inflammatory drugs is a major factor in their analgesic effects.
It should be emphasized that many of the drugs to be discussed here, with the exception of the opioids, are CNS depressants and might not be good analgesic. Tranquilizers, ataractics, and hypnotics can be used as adjuncts in the treatment of non-pain-induced stress and distress, but not for the treatment of pain. Many combinations of drugs have been used in various species for analgesia, sedation, restraint, and general anesthesia. Table 5-1 shows clinical uses of drugs in various classes included in this chapter.
The aim of general anesthesia is to produce unconsciousness as rapidly and as smoothly as possible and to maintain a depth of anesthesia appropriate for the objectives of the surgery or study. The depth of anesthesia might have to be varied on the basis of the intensity of the stimulation and changing physiologic conditions, as the anesthetist attempts to balance adequate anesthesia and analgesia with physiologic function. The level of anesthesia required can vary from moderate for surgical intervention to light for the study period that follows. Considerable information is available on the pharmacologic effects of anesthetic agents on organ functions in some species (Merin, 1975; Covino et al., 1985; Miller, 1990). General anesthesia can affect all physiologic functions; for inhalational anesthetics, the magnitude of the affects is related to the alveolar concentration of the specific drug.