THE ABDOMINAL CONSTRICTION RESPONSE AND ITS SUPPRESSION BY ANALGESIC DRUGS IN THE MOUSE

Abstract

After intraperitoneal injection of a noxious agent, the rat and the mouse show a response consisting of a wave of constriction and elongation passing caudally along the abdominal wall, sometimes accompanied by twisting of the trunk and followed by exten- sion of the hind limbs (Vander Wende & Margolin, 1956;Siegmund, Cadmus & Lu, 1957).This response has been variously called " writhing" (Vander Wende & Margolin, 1956), " stretching" (Koster, Anderson & de Beer, 1959), " cramping " (Murray & Miller, 1960} and " squirming " (Whittle, 1964a).Because of the emotional implications of these terms, it was later called the " abdominal constriction response " (Collier, Hammond, Horwood-Barrett & Schneider, 1964).We describe here an examination of the ability of a number of substances, including some occurring in tissues and causing pain in man (Keele & Armstrong, 1964), to elicit abdominal constriction responses in mice.Vander Wende & Margolin (1956) and Siegmund et al. (1957) showed that codeine, morphine and pethidine, given subcutaneously, and procaine, given intraperitoneally, suppressed the abdominal constriction response.They concluded that the response was nociceptive and they used it as a basis for testing analgesic drugs.The antinociceptive tests developed from this work have the advantage that they are sensitive to antipyretic drugs (Siegmund et al., 1957; Hendershot & Forsaith, 1959; Koster et at., 1959; Keith, 1960) and to narcotic antagonists (Taber, Greenhouse & Irwin, 1964; Blumberg, Wolf & Dayton, 1965; Pearl & Harris, 1966).These tests have, however, three disadvantages: (1) exposure of animals to peritoneal stimulation intense enough to induce repeated abdominal constrictions for longer than necessary is ethically undesirable and needlessly time consuming; (2) increased permeability of blood vessels accompanies peritoneal irritation (Northover, 1963(Northover, , 1964) and the development of abdominal constrictions (Whittle, 1963, 1964a and b), and so an antinociceptive effect cannot easily be distinguished from an anti-inflammatory; and (3) the test produces many false positives (Hendershot & Forsaith, 1959; Emele & Shanaman, 1963; Brittain, Lehrer & Spencer, 1963; Okun, Liddon & Lasagna, 1963).We describe new forms of abdominal constriction test in the mouse, in which some of these disadvantages are lessened.Preliminary accounts of this work have been published (Collier et al., 1964; Collier, James & Schneider, 1966). METHODSTable I gives the substances tested for ability to elicit the abdominal constriction response.Inorganic salts, acetic acid and ethanol were dissolved in distilled water; 1:4-phenylbenzoquinone 14765381a, 1968, 2, Downloaded from https://bpspubs.