British journal of pharmacology
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Comparative Study
Spinal effects of four injectable anaesthetics on nociceptive reflexes in rats: a comparison of electrophysiological and behavioural measurements.
1. To assess the direct spinal contributions to the depression of reflexes caused by general anaesthetics, the intravenous potency of four injectable anaesthetics has been compared in two preparations: in decerebrate, spinalised rats, using a novel preparation requiring little surgical intervention, and in intact rats with chronically implanted i.v. cannulae. 2. Methohexitone (1-8 mg kg-1 i.v.), alphaxalone/alphadolone (0.5-8 mg kg-1 i.v.), alpha-chloralose (20-80 mg kg-1 i.v.) and ketamine (0.5-16 mg kg-1 i.v.) all produced a dose-dependent depression of single motor unit activity evoked by controlled noxious mechanical stimuli in decerebrate, spinalised animals. 3. ⋯ However, additional doses of the maintenance anaesthetics were less effective than the same doses tested in decerebrate animals. 5. All the anaesthetics tested produced a significant depression of spinal reflex responses to noxious stimuli at doses well below those required for anaesthesia. Whilst the presence of maintenance anaesthetics appears not to distort pharmacological tests of other agents, there may nonetheless be a biasing of the samples of cells recorded.
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1. We have tested the hypothesis that capsaicin-induced activation, desensitization and impairment of peripheral nociceptor function is mediated by separate mechanisms. This was investigated by use of an in vitro preparation of the neonatal rat spinal cord with the functionally attached tail in which the cord and tail were separately superfused with physiological solution. ⋯ Extracellular calcium is not required for capsaicin-induced activation or desensitization but calcium as well as sodium are important for capsaicin-induced impairment of nociceptive responses. Desensitization may occur independently of peripheral fibre activation and cannot be attributed to a central mechanism. Finally neither capsaicin-induced activation nor desensitization require the participation of a second messenger.
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1. Kinins were measured by a radioimmunoassay in the inflammatory exudates induced by carrageenin or zymosan in the peritoneal cavity of normal Wistar rats and of kininogen-deficient Brown Norway rats. 2. After administration of carrageenin to normal rats, levels of immunoreactive kinins showed a single peak during the first two hours and then decreased. ⋯ During zymosan-induced peritonitis, the exudates were devoid of immunoreactive kinins in both species. The volume of the exudates was larger in kininogen-deficient rats than in normal rats. 5. We conclude that in rats, the kinin system is a major factor responsible for the development of the inflammatory reactions induced by carrageenin, but is not involved in the reactions induced by zymosan.
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1. The effects of intracisternal (i.c.) application of putative 5-hydroxytryptamine (5-HT)1A antagonists on the reflex bradycardia evoked by injection of phenylbiguanide (i.v.) were investigated in anaesthetized, atenolol-pretreated rats. 2. ⋯ The bradycardia was also attenuated by i.c. methiothepin (200 micrograms kg-1), (+/-)-pindolol (100 micrograms kg-1) and buspirone (200 micrograms kg-1) but was not attenuated by antagonists selective for alpha 1-adrenoceptors (alfuzosin; 100 micrograms kg-1), 5-HT2-receptors (BW 501C67; 100 micrograms kg-1) or dopamine D2-receptors ((-)-sulpiride; 100 micrograms kg-1) given i.c. 3. It is concluded that the 5-HT1A-receptor antagonist action of intracisternally applied spiperone, methiothepin, (+/-)-pindolol and buspirone is responsible for the ability of these drugs to attenuate reversibly the excitation of cardiac vagal motoneurones caused by activation of the von Bezold-Jarisch reflex.
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1. We have studied the effect of the calcium channel antagonist, diltiazem, on the coronary haemodynamic and cardiac functional responses produced by intracoronary (i.c.) administration of endothelin-1 (ET-1) in anaesthetized dogs. 2. ET-1, 1, 3 and 10 ng kg-1 i.c., produced dose-related increases in coronary blood flow with no cardiac functional or systemic haemodynamic changes. ⋯ At slightly higher doses ET-1 is also a coronary vasoconstrictor. ET-1 also appears to have direct cardiotoxicity independent of myocardial ischaemia. The vasoconstrictor activity and direct cardiotoxicity are only weakly inhibited by diltiazem.