Benzodiazepines Suppress Neuromodulatory Effects of Pudendal Nerve Stimulation on Rat Bladder Nociception
| Autor: | Buffie Clodfelder-Miller, Xin Su, Timothy J. Ness, Dwight E. Nelson, Jamie McNaught |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Flumazenil
Nociception Sensory Receptor Cells medicine.drug_class Midazolam Urinary Bladder Stimulation Article Rats Sprague-Dawley 03 medical and health sciences Benzodiazepines 0302 clinical medicine 030202 anesthesiology medicine Animals Bladder Pain GABA Modulators Motor Neurons Benzodiazepine Urinary bladder Diazepam Dose-Response Relationship Drug business.industry Muscle Smooth Neuromodulation (medicine) Electric Stimulation Pudendal Nerve Rats Anesthesiology and Pain Medicine medicine.anatomical_structure Opioid Anesthesia Female business 030217 neurology & neurosurgery medicine.drug Muscle Contraction |
| Zdroj: | Anesth Analg |
| ISSN: | 1526-7598 |
| Popis: | Background Neuromodulation, as a therapeutic modality for pain treatment, is an alternative to opioid therapies and therefore receiving increased interest and use. Neuromodulation at a peripheral nerve target, in the form of bilateral electrical pudendal nerve stimulation (bPNS), has been shown to reduce bladder hypersensitivity in rats and anecdotally reduces pain in humans with pelvic pain of urological origin. Recent studies have identified a role for spinal γ-aminobutyric acid (GABA) receptors in this effect. Concomitant medication use, such as benzodiazepines, could alter responses to neuromodulation, and so before the development of a clinical trial to confirm translation of this potential therapy, the potential interactions between acute and chronic use of benzodiazepines and bPNS were examined in a preclinical model. Methods Bladder hypersensitivity was produced by neonatal bladder inflammation in rat pups coupled with a second inflammatory insult as an adult. Diazepam (1-5 mg/kg intraperitoneal [i.p.]) or vehicle was administered acutely (with or without bPNS) and chronically (5 mg/kg subcutaneous [s.c.] daily for 2 weeks before the final experiment). bPNS was delivered as bilateral biphasic electrical stimulation of the mixed motor/sensory component of the pudendal nerves. Visceromotor responses (VMRs; abdominal muscle contractile responses to urinary bladder distension [UBD]) were used as nociceptive end points. Due to the profound effects of diazepam, the effect of midazolam (0.5-1.0 mg/kg i.p.) on VMRs and bPNS effects was also studied. Results Diazepam and midazolam both produced a dose-dependent, flumazenil-reversible inhibition of VMRs to UBD. bPNS resulted in statistically significant inhibition of VMRs to UBD in hypersensitive rats that had received vehicle injections. Select doses of diazepam and midazolam suppressed the inhibitory effect of bPNS on VMRs. Conclusions This study suggests that inhibitory effects of bPNS on bladder pain could be suppressed in subjects receiving benzodiazepine therapy, suggesting that potential clinical testing of pudendal nerve stimulation for the treatment of painful bladder syndromes may be confounded by the use of benzodiazepines. Clinical assessment of other forms of neuromodulation should also be screened for impacts of benzodiazepines. |
| Databáze: | OpenAIRE |
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