title: Modulation of cardiac ischemia-sensitive afferent neuron signaling by preemptive C2 spinal cord stimulation: effect on substance P release from rat spinal cord.
abstract: 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.
authors.affiliation: Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614-1708, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Ding
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Ardell
authors.forename: Fang
authors.initials: F
authors.lastname: Hua
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: McAuley
authors.forename: Kristopher
authors.initials: K
authors.lastname: Sutherly
authors.forename: Jala J
authors.initials: JJ
authors.lastname: Daniel
authors.forename: Carole A
authors.initials: CA
authors.lastname: Williams
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism; D002574:Cervical Vertebrae; D003331:Coronary Vessels / Q000503:physiopathology; D004558:Electric Stimulation; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D009475:Neurons, Afferent / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D017552:Solitary Nucleus / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D013904:Thoracic Vertebrae
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D013373:Substance P