title: Responses of thoracic spinal neurons to activation and desensitization of cardiac TRPV1-containing afferents in rats.
abstract: The purpose of this study was to examine how upper thoracic spinal neurons responded to activation and desensitization of cardiac transient receptor potential vanilloid-1 (TRPV1)-containing afferent fibers. Extracellular potentials of single T3 spinal neurons were recorded in pentobarbital-anesthetized, paralyzed, and ventilated male rats. To activate cardiac nociceptive receptors, a catheter was placed in the pericardial sac to administer various chemicals: bradykinin (BK; 10 microg/ml, 0.2 ml), capsaicin (CAP, 10 microg/ml, 0.2 ml), or a mixture of algesic chemicals (AC; 0.2 ml) containing adenosine 10(-3) M, BK, serotonin, histamine, and PGE(2), 10(-5) M for each. Spinal neurons that responded to intrapericardial BK and/or CAP were used in this study. Results showed that 81% (35/43) of the neurons had excitatory responses to both intrapericardial BK and CAP, and the remainder responded to either BK or CAP. Intrapericardial resiniferatoxin (RTX) (0.2 microg/ml, 0.2 ml, 1 min), which desensitizes TRPV1-containing nerve endings, abolished excitatory responses to both BK (n = 8) and CAP (n = 7), and to AC (n = 5) but not to somatic stimuli. Intrapericardial capsazepine (1 mg/ml, 0.2 ml, 3 min), a specific antagonist of TRPV1, sharply attenuated excitatory responses to CAP in 5/5 neurons, but responses to BK in 5/5 neurons was maintained. Additionally, intrapericardial capsazepine had no significant effect on excitatory responses to AC in 3/3 neurons. These data indicated that intrapericardial BK-initiated spinal neuronal responses were linked to cardiac TRPV1-containing afferent fibers, but were not dependent on TRPV1. Intraspinal signaling for cardiac nociception was mediated through CAP-sensitive afferent fibers innervating the heart.
authors.affiliation: Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA. chao-qin@ouhsc.edu
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.forename: Jay P
authors.initials: JP
authors.lastname: Farber
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Miller
authors.forename: Robert D
authors.initials: RD
authors.lastname: Foreman
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D006321:Heart / Q000294:innervation* / Q000502:physiology*; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D013127:Spinal Nerves / Q000502:physiology*; D050916:TRPV Cation Channels / Q000378:metabolism*; D013904:Thoracic Vertebrae / Q000502:physiology
chemical_list: D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat