title: Effect of sildenafil on neuropathic pain and hemodynamics in rats.
abstract: OBJECTIVE
  The inhibition of phosphodiesterase 5 produces an antinociception through the increase of cyclic guanosine monophosphate (cGMP), and increasing cGMP levels enhance the release of gamma-aminobutyric acid (GABA). Furthermore, this phosphodiesterase 5 plays a pivotal role in the regulation of the vasodilatation associated to cGMP. In this work, we examined the contribution of GABA receptors to the effect of sildenafil, a phosphodiesterase 5 inhibitor, in a neuropathic pain rat, and assessed the hemodynamic effect of sildenafil in normal rats.
  
  
  METHODS
  Neuropathic pain was induced by ligation of L5/6 spinal nerves in Sprague-Dawley male rats. After observing the effect of intravenous sildenafil on neuropathic pain, GABAA receptor antagonist (bicuculline) and GABAB receptor antagonist (saclofen) were administered prior to delivery of sildenafil to determine the role of GABA receptors in the activity of sildenafil. For hemodynamic measurements, catheters were inserted into the tail artery. Mean arterial pressure (MAP) and heart rate (HR) were measured over 60 min following administration of sildenafil.
  
  
  RESULTS
  Intravenous sildenafil dose-dependently increased the withdrawal threshold to the von Frey filament application in the ligated paw. Intravenous bicuculline and saclofen reversed the antinociception of sildenafil. Intravenous sildenafil increased the magnitude of MAP reduction at the maximal dosage, but it did not affect HR response.
  
  
  CONCLUSIONS
  These results suggest that sildenafil is active in causing neuropathic pain. Both GABAA and GABAB receptors are involved in the antinociceptive effect of sildenafil. Additionally, intravenous sildenafil reduces MAP without affecting HR.
authors.affiliation: The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Dong-gu, Gwangju, Korea.
authors.forename: Lan Ji
authors.initials: LJ
authors.lastname: Huang
authors.forename: Myung Ha
authors.initials: MH
authors.lastname: Yoon
authors.forename: Jeong Il
authors.initials: JI
authors.lastname: Choi
authors.forename: Woong Mo
authors.initials: WM
authors.lastname: Kim
authors.forename: Hyung Gon
authors.initials: HG
authors.lastname: Lee
authors.forename: Yeo Ok
authors.initials: YO
authors.lastname: Kim
mesh_terms: D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D017288:Pain Threshold / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*
chemical_list: D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D013450:Sulfones; D000068677:Sildenafil Citrate; D001418:Baclofen; C080629:saclofen; D001640:Bicuculline