Modulation of cardiac ischemia-sensitive afferent neuron signaling by preemptive C2 spinal cord stimulation: effect on substance P release from rat spinal cord

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 294; no. 1; pp. R93 - R101
• Main Authors: Ding, XiaoHui, Ardell, Jeffrey L, Hua, Fang, McAuley, Ryan J, Sutherly, Kristopher, Daniel, Jala J, Williams, Carole A
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.01.2008
• Subjects: Angina pectoris; Animals; Brain Stem - metabolism; Cervical Vertebrae; Coronary Vessels - physiopathology; Electric Stimulation; Male; Myocardial Ischemia - metabolism; Neurons; Neurons, Afferent - physiology; Peptides; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Sprague-Dawley; Rodents; Signal Transduction - physiology; Solitary Nucleus - physiology; Spinal cord; Spinal Cord - metabolism; Substance P - metabolism; Thoracic Vertebrae
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00544.2007

Departments of 1 Physiology, 2 Pharmacology, and 3 Surgery and Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee Submitted 30 July 2007 ; accepted in final form 6 November 2007 The upper cervical spinal region functions as an intraspinal controller of thoracic spinal reflexes and contributes to neuronal regulation of the ischemic myocardium. Our objective was to determine whether stimulation of the C2 cervical spinal cord (SCS) of rats modified the input signal at the thoracic spinal cord when cardiac ischemia-sensitive (sympathetic) afferents were activated by transient occlusion of the left anterior descending coronary artery (CoAO). Changes in c-Fos expression were used as an index of neuronal activation within the spinal cord and brain stem. The pattern of substance P (SP) release, a putative nociceptive transmitter, was measured using antibody-coated microprobes. Two SCS protocols were used: reactive SCS, applied concurrently with intermittent CoAO and preemptive, sustained SCS starting 15 min before and continuing during the repeated intermittent CoAO. CoAO increased SP release from laminae I and II in the T4 spinal cord above resting levels. Intermittent SCS with CoAO resulted in greater levels of SP release from deeper laminae IV–VII in T4 than CoAO alone. In contrast, SP release from laminae I and II was inhibited when CoAO was applied during preemptive, sustained SCS. Preemptive SCS likewise reduced c-Fos expression in the T4 spinal cord (laminae I–V) and nucleus tractus solitarius but increased expression in the intermediolateral cell column of T4 compared with CoAO alone. These results suggest that preemptive SCS from the high cervical region modulates sensory afferent signaling from the ischemic myocardium. antibody-coated microprobes; angina; nociceptive peptides; cardiac nervous system; c-Fos expression Address for reprint requests and other correspondence: C. A. Williams, Dept. of Physiology, Quillen College of Medicine, East Tennessee State Univ., Stanton-Gerber Hall B-137, PO Box 70576, Johnson City, TN 37614-1708 (e-mail: williams{at}etsu.edu )