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 E(2)(PGE(2)) (total 25 nmol in 25 mu l) 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 PGE(2) 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 mu l). Both BK and the mixture containing BK produced dose-dependent cardiovascular responses (presser 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. AH 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.