Life sciences
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We report a nociceptive test involving peripheral irritation which produces behavior similar to that elicited by intrathecally injected substance P. Intradermal hypertonic saline injected to the lower abdominal area produced quantifiable behavior in mice. The behavior consisted of licking, biting and scratching directed to the location of i.d. injection, and was dose-dependent with respect to the concentration and volume of saline. ⋯ The behavior was not blocked by non-steroidal anti-inflammatory agents. This nociceptive test, in conjunction with the substance P-induced behavior test, may allow discrimination between agents acting pre- or post-synaptically in the spinal cord. Baclofen, a GABAB agonist thought to act presynaptically, changed substance P-induced behavior and hypertonic saline-induced behavior in opposite directions.
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The literature provides considerable evidence indicating that several, but not all antihistaminics, are indeed analgesic agents and some are analgesic adjuvants as well. Those for which effectiveness is reported includes diphenhydramine, hydroxyzine, orphenadrine, pyrilamine, phenyltoloxamine, promethazine, methdilazine, and tripelennamine. The proposed mechanisms of analgesic action of antihistaminics are reviewed and discussed. ⋯ The evidence for a role for norepinephrine and dopamine and the effects of antihistaminics on them are less well established. Still other pathways have been proposed. A greater understanding of pain mechanisms will aid in elucidating the role of antihistaminics in analgesia.
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Normal chicken heart mesenchymal cells at low density in monolayer culture in plasma-containing medium have a polygonal shape and are proliferatively quiescent. The combination of epidermal growth factor and insulin at hyperphysiological concentration, an insulin-like growth factor surrogate, causes these cells to assume a fusiform shape and to increase 40-fold in number during four days of incubation. These mitogenic hormones do not, however, induce normal chicken heart mesenchymal cells to form colonies in agarose suspension culture. ⋯ Infection with avian leukosis viruses (RAV-1, RAV-2, RPL-42) or with transformation-defective mutants of Rous sarcoma virus (tdNY105, 107, 109) does not affect the morphology or proliferative behavior of chicken heart mesenchymal cells. Monolayer culture of chicken heart mesenchymal cells in plasma-containing medium appears, therefore, to define the ability of onc genes of acute transforming avian retroviruses to induce autonomous (mitogenic hormone-independent) cell proliferation, the essential characteristic of neoplasia. The differences in transformed morphology and rates of autonomous proliferation between cells infected with different acute transforming retroviruses probably reflects differences in the modes of action of the transforming proteins encoded by the onc genes of the respective viruses.(ABSTRACT TRUNCATED AT 400 WORDS)
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The effect of the diterpene forskolin on vascular permeability alone and in combination with bradykinin, prostaglandin E1, adenosine or histamine has been investigated in rats. Vascular permeability in rat skin was measured using [125I]-labelled bovine serum albumin ([125I]BSA) as a tracer. In addition, the effect of forskolin on footpad edema induced by the injection of a mixture of 2% carrageenin was determined. ⋯ Parenteral administration of a prostaglandin synthetase inhibitor, indomethacin, suppressed the footpad edema induced with carrageenin, but did not inhibit the footpad edema induced with a mixture of carrageenin and forskolin. An antihistamine, cyproheptadine, had no effect on carrageenin-induced footpad edema either in the presence or absence of forskolin. These results suggest that both bradykinin and prostaglandins are essential for the development of carrageenin-induced footpad edema and that bradykinin plays an important role in the potentiative effect of forskolin on footpad edema induced with carrageenin in rats.
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Subcutaneous administrations of naloxone and naltrexone have already been shown to enhance nociceptive reactions in mice. The present study was undertaken to examine the effects of N-methyl-naloxone and N-methylnaltrexone on nociception using the hot plate test (dose range: 0.3 to 30 mg kg-1s.c.). The latter compounds were selected to differentiate the central and peripheral components of hyperalgesia. ⋯ Further, N-methylnaloxone and N-methylnaltrexone were very weak in precipitating the signs of abstinence in mice rendered acutely dependent on morphine. Two factors, poorer penetration into the CNS and steric hindrance, might render the N-methylated antagonists weak. Hence, both these factors should be considered when interpreting the effects after quaternary derivatives of opioid antagonists.