title: Role of the endogenous opioid system in modulation of urinary bladder activity by spinal nerve stimulation.
abstract: The role of the endogenous opioid system in modulation of urinary bladder activity by spinal nerve (SN) stimulation was studied in anesthetized female rats, using the rat model of isovolumetric bladder contraction. SN stimulation at a fixed frequency of 10 Hz attenuated bladder contraction frequency; the magnitude of the inhibition was directly proportional to the current intensity. Neither the κ-opioid antagonist nor-binaltorphimine (2 mg/kg iv) nor the δ-opioid antagonist naltrindole (5 mg/kg iv) attenuated the bladder inhibitory response to SN stimulation. In contrast, the μ-opioid receptor antagonist naloxone (NLX; 0.03 mg/kg iv) blocked the inhibitory responses evoked by SN stimulation at therapeutic current intensities at ≤1 × motor threshold current (Tmot). An action at spinal and supraspinal centers was further confirmed by the ability of intrathecal or intracerebroventricular administration of NLX methiodide to attenuate the bladder inhibitory effects of 1 × Tmot SN stimulation. The magnitude of SN-mediated neuromodulation using therapeutically relevant stimulation intensity (Tmot) is equivalent to 0.16 mg/kg of systemically administered morphine, which produces 50% inhibition of bladder contraction frequency. These results suggest that the inhibitory effects of lower intensity SN stimulation may be mediated through the release of endogenous μ-opioid peptides. Additionally, these data suggest that neuromodulation may offer a mode of treating the symptoms of overactive bladder with efficacy equal to the opioid drugs but without their liability for abuse and dependence.
authors: Medtronic, Incorporated, Neuromodulation Research, 7000 Central Ave. NE, RCE470, Minneapolis, MN 55432, USA. xin.su@medtronic.com
authors: Xin
authors: X
authors: Su
authors: Angela
authors: A
authors: Nickles
authors: Dwight E
authors: DE
authors: Nelson
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects; D018847:Opioid Peptides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D013127:Spinal Nerves / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D001743:Urinary Bladder / Q000294:innervation*; D014554:Urination
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; C051844:norbinaltorphimine; D009271:Naltrexone; D009020:Morphine; C055382:naltrindole
keywords: bladder; electrical stimulation; micturition; opioid; spinal nerve
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