title: Substance P release in response to cardiac ischemia from rat thoracic spinal dorsal horn is mediated by TRPV1.
abstract: Spinal cord stimulation (SCS) inhibits substance P (SP) release and decreases the expression of the transient receptor potential vanilloid 1 (TRPV1) in the spinal cord at thoracic 4 (T4) during cardiac ischemia in rat models (Ding et al., 2007). We hypothesized that activation of TRPV1 in the T4 spinal cord segment by intermittent occlusion of the left anterior descending coronary artery (CoAO) mediates spinal cord SP release. Experiments were conducted in urethane-anesthetized Sprague-Dawley male rats using SP antibody-coated microprobes to measure SP release at the central terminal endings of cardiac ischemic-sensitive afferent neurons (CISAN) in the spinal T4 dorsal horns. Vehicle, capsaicin (CAP; TRPV1 agonist) and capsazepine (CZP; TRPV1 antagonist) were injected into the left T4 prior to stimulation of CISAN by intermittent CoAO (with or without upper cervical SCS). CAP induced endogenous SP release from laminae I and II in the T4 spinal cord above baseline. Conversely, CZP injections significantly inhibited SP release from laminae I-VII in the T4 spinal cord segment below baseline. CZP also attenuated CoAO-induced SP release, while T4 injections of CZP with SCS completely restored SP release to basal levels during CoAO activation. CAP increased the number of c-Fos (a marker for CISAN activation) positive T4 dorsal horn neurons compared to sham-operated animals, while CZP (alone or during CoAO and SCS+CoAO) significantly reduced the number of c-Fos positive neurons. These results suggest that spinal release of the putative nociceptive transmitter SP occurs, at least in part, via a TRPV1 mechanism.
authors.affiliation: Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614-1708, United States. steagall@etsu.edu
authors.forename: R J
authors.initials: RJ
authors.lastname: Steagall
authors.forename: A L
authors.initials: AL
authors.lastname: Sipe
authors.forename: C A
authors.initials: CA
authors.lastname: Williams
authors.forename: W L
authors.initials: WL
authors.lastname: Joyner
authors.forename: K
authors.initials: K
authors.lastname: Singh
mesh_terms: D000818:Animals; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D020671:Posterior Horn Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism; D013373:Substance P / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D013904:Thoracic Vertebrae
chemical_list: D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D013373:Substance P