British journal of pharmacology
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Comparative Study
The contribution of NMDA receptor activation to spinal c-Fos expression in a model of inflammatory pain.
1. Intraplantar carrageenin (6 mg 150 microliters-1) evoked a high level of spinal c-Fos expression in the dorsal horn, of segments L4-L5 of the spinal cord, and an extensive peripheral oedema; both parameters were assessed 3 h after carrageenin. 2. Two series of experiments were performed, with the mean total number of Fos like-immunoreactive neurones (Fos-LI), after carrageenin, not being significantly different for the two series of experiments (266 +/- 17 and 332 +/- 31 Fos-LI neurones). ⋯ A single post-administration of (+)-HA966 (10 mg kg-1), 45 min after intraplantar carrageenin, did not significantly influence the number of Fos-LI neurones in the superficial, deep laminae or ventral horn, but significantly reduced the number of Fos-LI neurones in the nucleus proprius, as compared tocontrol carrageenin expression (39+-/8% reduction of control carrageenin c-Fos expression, P <0.05).9 None of the concentrations of (+)-HA966 studied, irrespective of the timing of administration,influenced the peripheral carrageenin oedema. Our results illustrate a contribution of central NMDA receptor activation to carrageenin-evoked spinal c-Fos expression. These results extend previous studies demonstrating the contribution of the NMDA receptor to central hyperalgesia and the expression of c-Fos.
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1. Peripheral inflammation is associated with the local production of neuroactive inflammatory cytokines and growth factors. These may contribute to inflammatory pain and hyperalgesia by directly or indirectly altering the function or chemical phenotype of responsive primary sensory neurones. 2. ⋯ Anti-NGF pretreatment substantially reduced CFA-induced mechanical and thermal hyperalgesia without reducing the elevation in IL-1 beta. 9. Intraplantar NGF (0.02, 0.2 and 2 microg) injections produced a short lasting thermal and mechanical hyperalgesia but did not change IL-1beta levels in the hindpaw skin.10. Our results demonstrate that IL-1beta contributes to the upregulation of NGF during inflammation and that NGF has a major role in the production of inflammatory pain hypersensitivity.
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1. We have investigated the novel naturally occurring marine compound, IZP-94005 (contignasterol), as a potential anti-asthma agent, using both in vivo and in vitro models of allergen-induced bronchoconstriction and airway smooth muscle contraction. 2. Tracheal rings from ovalbumin (OA)-sensitized guinea-pigs were treated with various concentrations of IZP-94005 for 20 min prior to challenge with ovalbumin. ⋯ IZP-94005 (50 and 200 micrograms kg-1), by inhalation 20 min prior to OA challenge caused significant inhibition of the increase in lung resistance induced by OA in sensitized guinea-pigs, compared to vehicle-treated animals. Nedocromil sodium (20 mg kg-1), with a similar protocol, also inhibited OA-induced responses in this model. 6. We therefore suggest that IZP-94005 is a good candidate for further investigation as a possible antiasthma agent.
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Comparative Study
Dose-response comparisons of five lung surfactant factor (LSF) preparations in an animal model of adult respiratory distress syndrome (ARDS).
1. We have examined the effects of five different lung surfactant factor (LSF) preparations in the rat lung lavage model. In this model repetitive lung lavage leads to lung injury with some similarities to adult respiratory distress syndrome with poor gas exchange and protein leakage into the alveolar spaces. ⋯ The bovine and the Recombinant LSF are superior to both synthetic LSFpreparations.5. In this animal model and under the described specific ventilatory settings, even between bovine LSFpreparations there are detectable differences that are pronounced when compared to synthetic LSFwithout any surfactant proteins. We conclude that the difference between bovine and synthetic LSFpreparations can be overcome by addition of the surfactant protein C.
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1. In the absence of adenosine uptake inhibition, adenosine produced a concentration-dependent (threshold 30 microM) relaxation of the 5-methylfurmethide pre-contracted guinea-pig taenia caecum. The relaxation was not blocked by 8-phenyltheophylline (8-PT, 3 microM) or 1,3-dipropyl, 8-cyclopentylxanthine (DPCPX, 30 microM). 2. ⋯ Therefore the amplification of the first phase responses by DPCPX did not appear to be due to phosphodiesterase inhibition.5. It was not possible to conclude whether second phase responses to adenosine and NECA were mediated by intracellular or extracellular sites of action. However, if intracellular sites of action were involved then adenosine did not apparently gain access by the Dip-sensitive uptake system.