title: Peripheral nociception associated with surgical incision elicits remote nonischemic cardioprotection via neurogenic activation of protein kinase C signaling.
abstract: BACKGROUND
  Although remote ischemic stimuli have been shown to elicit cardioprotection against ischemia/reperfusion injury, there is little known about the effects of nonischemic stimuli. We previously described a remote cardioprotective effect of nonischemic surgical trauma (abdominal incision) called remote preconditioning of trauma (RPCT). In the present study, we elucidate mechanisms underlying this phenomenon.
  
  
  RESULTS
  We used a murine model of myocardial infarction to evaluate ischemia/reperfusion injury, and either abdominal surgical incision, or application of topical capsaicin, to elicit cardioprotection. We show that the cardioprotective effect of RPCT is initiated by skin nociception, and requires neurogenic signaling involving spinal nerves and activation of cardiac sensory and sympathetic nerves. Our results demonstrate bradykinin-dependent activation and repression, respectively, of PKCepsilon and PKCdelta in myocardium after RPCT, and we show involvement of the K(ATP) channels in cardioprotection. Finally, we show that topical application of capsaicin, which selectively activates C sensory fibers in the skin, mimics the cardioprotective effect of RPCT against myocardial infarction.
  
  
  CONCLUSIONS
  Nontraumatic nociceptive preconditioning represents a novel therapeutic strategy for cardioprotection with great potential clinical utility.
authors.affiliation: Department of Pharmacology and Cell Biophysics, University of Cincinnati, OH 45267-0575, USA.
authors.forename: W Keith
authors.initials: WK
authors.lastname: Jones
authors.forename: Guo-Chang
authors.initials: GC
authors.lastname: Fan
authors.forename: Siyun
authors.initials: S
authors.lastname: Liao
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Neal L
authors.initials: NL
authors.lastname: Weintraub
authors.forename: Evangelia G
authors.initials: EG
authors.lastname: Kranias
authors.forename: Jo El
authors.initials: JE
authors.lastname: Schultz
authors.forename: John
authors.initials: J
authors.lastname: Lorenz
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Ren
mesh_terms: D000818:Animals; D017209:Apoptosis; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000294:innervation*; D019194:Ischemic Preconditioning / Q000379:methods*; D054086:KATP Channels / Q000378:metabolism; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010146:Pain / Q000503:physiopathology*; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D054086:KATP Channels; D011493:Protein Kinase C; D002211:Capsaicin