title: Acute sacral nerve stimulation reduces visceral mechanosensitivity in Rat through spinal opioid pathway.
abstract: BACKGROUND
  Sacral nerve stimulation (SNS) is an alternative surgical treatment of refractory urge incontinence and/or fecal incontinence. Despite its clinical efficacy, the mechanisms of action of SNS remain poorly understood. The aim of this experimental study was to evaluate the effect of SNS on visceral mechanosensitivity in rats.
  
  
  METHODS
  Anesthetized Sprague-Dawley rats were treated with SNS or sham stimulation. SNS was performed by implanting an electrode close to the sacral nerve root S1. Rats were administered either a non-selective opioid receptor antagonist (naloxone) or a nitric oxide synthase inhibitor (L-NAME). Colonic mechanosensitivity was evaluated using the variation of arterial blood pressure as a spino-bulbar reflex in response to graded isobaric colorectal distension (CRD). C-fos immunoreactive neurons were quantified in spinal and supraspinal sites. μ-opioid receptor (MOR) internalization was counted in the sacral spinal cord with sham or effective SNS in response to CRD.
  
  
  RESULTS
  SNS reduced visceral mechanosensitivity in response to CRD. This effect was reversed by intrathecal and intraveinous naloxone administration. In both models, CRD induced increased c-fos immunoreactivity in the dorsal horn neurons of the sacral spinal cord and supraspinal areas. This increase was prevented by SNS. MOR internalization was significantly higher in stimulated group.
  
  
  CONCLUSIONS
  SNS impacts on visceral mechanosensitivity by decreasing the spino-bulbar reflex in response to CRD. Spinal opioid receptors are likely involved in this effect.
authors: Nutrition, Gut & Brain Unit (INSERM U1073), Institute for Biomedical Research and Innovation, Rouen University, Rouen, France.
authors: L
authors: L
authors: Langlois
authors: Nutrition, Gut & Brain Unit (INSERM U1073), Institute for Biomedical Research and Innovation, Rouen University, Rouen, France.
authors: M
authors: M
authors: Meleine
authors: Nutrition, Gut & Brain Unit (INSERM U1073), Institute for Biomedical Research and Innovation, Rouen University, Rouen, France.
authors: W
authors: W
authors: Ouelaa
authors: Department of Urology, Rouen University Hospital, Rouen, France.
authors: R
authors: R
authors: Caremel
authors: Nutrition, Gut & Brain Unit (INSERM U1073), Institute for Biomedical Research and Innovation, Rouen University, Rouen, France.|Department of Digestive Surgery, Rouen University Hospital, Rouen, France.
authors: V
authors: V
authors: Bridoux
authors: Cell Imaging Platform of Normandy (PRIMACEN), Mont-Saint-Aignan, France.
authors: M
authors: M
authors: Benard
authors: Nutrition, Gut & Brain Unit (INSERM U1073), Institute for Biomedical Research and Innovation, Rouen University, Rouen, France.
authors: P
authors: P
authors: Dechelotte
authors: Nutrition, Gut & Brain Unit (INSERM U1073), Institute for Biomedical Research and Innovation, Rouen University, Rouen, France.|Department of Gastroenterology, Rouen University Hospital, Rouen, France.
authors: P
authors: P
authors: Ducrotte
authors: Department of Urology, Rouen University Hospital, Rouen, France.
authors: P
authors: P
authors: Grise
authors: Nutrition, Gut & Brain Unit (INSERM U1073), Institute for Biomedical Research and Innovation, Rouen University, Rouen, France.|Department of Physiology, Rouen University Hospital, Rouen, France.
authors: A M
authors: AM
authors: Leroi
authors: Nutrition, Gut & Brain Unit (INSERM U1073), Institute for Biomedical Research and Innovation, Rouen University, Rouen, France.|Department of Physiology, Rouen University Hospital, Rouen, France.
authors: G
authors: G
authors: Gourcerol
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D003106:Colon; D004106:Dilatation; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006930:Hyperalgesia / Q000378:metabolism*; D008160:Lumbosacral Plexus; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012018:Reflex; D012445:Sacrococcygeal Region; D012684:Sensory Thresholds / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D059265:Visceral Pain / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009270:Naloxone; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester
keywords: colorectal distension; opioid; rat; sacral nerve stimulation