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Neuromodulatory effects of pudendal nerve stimulation on bladder hypersensitivity are present in opioid-pretreated rats
  1. Timothy John Ness1,
  2. Jamie McNaught1,
  3. Buffie Clodfelder-Miller1,
  4. Dwight E Nelson2 and
  5. Xin Su2
  1. 1Anesthesiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
  2. 2Global Neuromodulation Research, Medtronic, Inc, Minneapolis, Minnesota, USA
  1. Correspondence to Dr Timothy John Ness, Anesthesiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; tness{at}


Background and objectives Bilateral electrical pudendal nerve stimulation (bPNS) reduces bladder hypersensitivity in rat models and anecdotally reduces pain in humans with pelvic pain of urologic origin. Concomitant opioids are known to alter responses to neuromodulation in some systems. So prior to the development of a clinical trial for purposes of regulatory approval, the preclinical interaction between opioids and stimulation effectiveness was examined.

Methods Bladder hypersensitivity was produced by neonatal bladder inflammation in rat pups coupled with a second inflammatory insult as an adult. Morphine was administered acutely (1–4 mg/kg intraperitoneal) or chronically (5 mg/kg subcutaneously daily for 2 weeks prior to the terminal experiment). bPNS consisted of bilateral biphasic electrical stimulation of the mixed motor/sensory component of the pudendal nerves. Visceromotor responses (VMR; abdominal muscle contractile responses to urinary bladder distension (UBD)) were used as nociceptive endpoints.

Results Morphine produced a dose-dependent inhibition of VMRs to UBD that was naloxone reversible. bPNS resulted in statistically significant inhibition of VMRs to UBD in hypersensitive rats that had received acute or chronic subcutaneous morphine injections.

Conclusions This study suggests that inhibitory effects of bPNS can still be evoked in subjects who are receiving opioid therapy, thus giving guidance to potential clinical trials seeking regulatory approval for the treatment of chronic bladder pain.

  • urinary bladder pain
  • neuromodulation
  • pudendal nerve

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  • Contributors TJN was involved in the planning, conduct, reporting, conception, design, acquisition, analysis and interpretation of data as well as drafting and revision of the manuscript. JMN and BCM were involved in the acquisition and analysis of data and revision of the manuscript. DEN and XS were both involved in the planning, conduct, reporting, conception, design and interpretation of data as well as revision of the manuscript. Technical assistance was also provided by Cary DeWitte.

  • Funding This study was supported by a contract from Medtronic, Inc. to the University of Alabama at Birmingham.

  • Competing interests XS and DEN were employees of Medtronic which funded this study.

  • Patient consent for publication Not required.

  • Ethics approval All studies were approved by the University of Alabama at Birmingham Institutional Animal Care and Utilization Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.