Acute sacral nerve stimulation reduces visceral mechanosensitivity in Rat through spinal opioid pathway

Neurogastroenterol Motil. 2015 Jun;27(6):816-23. doi: 10.1111/nmo.12555. Epub 2015 Mar 25.

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.

Key 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 & inferences: SNS impacts on visceral mechanosensitivity by decreasing the spino-bulbar reflex in response to CRD. Spinal opioid receptors are likely involved in this effect.

Keywords: colorectal distension; opioid; rat; sacral nerve stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterial Pressure / drug effects
  • Colon
  • Dilatation
  • Electric Stimulation*
  • Enzyme Inhibitors / pharmacology
  • Hyperalgesia / metabolism*
  • Lumbosacral Plexus*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Neurons / drug effects
  • Neurons / metabolism
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / metabolism*
  • Proto-Oncogene Proteins c-fos
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid / metabolism
  • Receptors, Opioid, mu / metabolism*
  • Reflex
  • Sacrococcygeal Region
  • Sensory Thresholds / drug effects
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism*
  • Visceral Pain / metabolism*

Substances

  • Enzyme Inhibitors
  • Narcotic Antagonists
  • Proto-Oncogene Proteins c-fos
  • Receptors, Opioid
  • Receptors, Opioid, mu
  • Naloxone
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester