A model of cardiac nociception in chronically instrumented rats: behavioral and electrophysiological effects of pericardial administration of algogenic substances.
This report presents evidence that pericardial administration of a mixture of algogenic substances is a potentially useful model of cardiac nociception. In awake rats in which a looped silicone catheter had been placed in the pericardial sac at least 5 days previous, administration of a mixture containing equal concentrations of bradykinin (BK), acetylcholine (ACh), adenosine (ADEN), histamine (HIST), serotonin (5-HT) and prostaglandin E2 (PGE2) (total 25 nmol in 25 microliters) led to rapid acquisition of a passive avoidance behavior. In contrast, neither BK alone (5-25 nmol) nor the same mixture of ACh, ADEN, HIST, 5-HT and PGE2 without BK led to acquisition of the behavior or produced effects significantly different than produced by saline given into the pericardial sac in the same volume (25 microliters). Both BK and the mixture containing BK produced dose-dependent cardiovascular responses (pressor response and tachycardia) of similar magnitude. Neither saline nor the mixture without BK produced significant changes in mean arterial blood pressure or heart rate. In electrophysiological experiments in the same rats, thoracic spinal cord neurons responded dose-dependently to the mixture and, except for one neuron, responded also to BK in a dose-dependent manner. However, responses to BK, when compared to a similar dosage of BK contained in the mixture, were significantly less in magnitude and duration. All units received convergent somatic input from the thorax and all neurons also received convergent input from the esophagus. Balloon distension of the esophagus excited all units. Results of the behavioral characterization of algogenic substances administered into the pericardial sac of awake rats gave evidence of differences between the effects of BK and a mixture of six substances, including BK. BK in either of two dosages tested produced effects not different than saline while the mixture containing BK was aversive. In complementary electrophysiological studies, both BK and the mixture containing BK excited thoracic spinal cord neurons, suggesting that neuron responses to putative algogenic substances are not necessarily reliable measures of cardiac nociception.
Department of Pharmacology, University of Iowa, College of Medicine, Iowa City, LA 52242 USA.
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Euchner-Wamser
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Meller
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Gebhart
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology; D002404:Catheterization; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004594:Electrophysiology; D006321:Heart / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D007267:Injections; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000139:chemically induced*; D010496:Pericardium / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D001920:Bradykinin