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Recognition and Alleviation of Pain and Distress in Laboratory Animals
(ibuprofen [Motrin®] and fenoprofen [Nalfon®]), naphthylpropionic acids (naproxen [Naprosyn®]), indoles (indomethacin [Indocin®]), and p-aminophenols (acetaminophen [Tylenol®]).
The nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the treatment of myositis, arthritis, and other surgical and nonsurgical acute and chronic inflammatory conditions (Table 5-9). The NSAIDs are the preferred drugs for the treatment of acute and chronic inflammatory conditions, because they do not interfere with the secretion of glucocorticoids from the adrenal gland, as do the steroid drugs.
The analgesic, antipyretic, and anti-inflammatory actions of NSAIDs are attributable mainly to inhibition of prostaglandin synthesis in the peripheral nervous system and CNS (e.g., antipyresis by inhibition of prostaglandin synthesis in the thermoregulatory center). Acetaminophen, however, is considered to have poor anti-inflammatory activity, because it is a weak prostaglandin synthetase inhibitor in vitro. The pain produced by the inflammatory process is mediated through endogenous eicosanoids and other substances (see Chapter 2). Many of the products of eicosanoid metabolism are responsible for the classic signs of the inflammatory process: redness, pain, and edema. Eicosanoids, released as a consequence of injury, produce vasodilation, increase in capillary permeability, edema, and leukocyte migration, which are associated with the pain produced by inflammation. The eicosanoids are not stored in cells, and their synthesis is initiated by the enzymatic release of fatty acids from cellular phospholipids (Higgins, 1985; Moore, 1985). The release of arachidonic acid from membrane phospholipids is the first event in the synthesis of the eicosanoids. Cyclo-oxygenase catalyzes the initial formation of prostaglandin from arachidonic acid. 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. For example, the release of the eicosanoids or their blockage has an effect on the microcirculation, producing vasodilation or vasoconstriction. NSAIDs interfere with or modify the effects of many drugs that depend on the release of eicosanoids.
The postoperative use of NSAIDs to minimize inflammation associated with surgical trauma is encouraged. But they have a broad effect on the arachidonic acid cascade, so they can modify the actions of many drugs and normal physiologic activity that might be under study. Because they do not produce obvious behavioral changes, as do many other drugs used for the relief of pain and distress, these