Tramadol enhances urethral continence function through µ-opioid receptors in rats.
OBJECTIVE
(±)-Tramadol hydrochloride (tramadol) is a widely used analgesic that stimulates the µ-opioid receptor and inhibits the reuptake of serotonin and noradrenalin. Although tramadol is also known to inhibit the micturition reflex in rats, its effects on urethral continence function have not been reported. We therefore examined whether intravenous tramadol (1, 3, and 10 mg/kg) affects intraurethral pressure, bladder leak point pressure, and leak volume in urethane-anesthetized female rats.


METHODS
(1) The intraurethral pressure was recorded with a microtip pressure transducer placed at the maximum pressure zone of the intrinsic urethral sphincter. (2) Gentle pressure was directly applied to the saline-filled bladder with a cotton bud until leakage occurred, and the bladder pressure at the moment of leakage was taken as the bladder leak point pressure. (3) The leak volume was measured as the amount of fluid leakage from the urethral orifice after electrical stimulation of abdominal muscles.


RESULTS
Tramadol significantly increased the intraurethral pressure. Both tramadol and morphine increased the bladder leak point pressure and decreased the leak volume. These changes were reversed by subcutaneous pretreatment with naloxone.


CONCLUSIONS
Tramadol improved urethral function and inhibited urinary incontinence through µ-opioid receptors.
Discovery Research Laboratories, Nippon Shinyaku Co., Ltd., Kisshoin, Minami-ku, Kyoto, Japan. t.oyama@po.nippon-shinyaku.co.jp
Tatsuya
T
Oyama
Yuko
Y
Kawai
Michiko
M
Oka
D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D005260:Female; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists*; D014147:Tramadol / Q000494:pharmacology / Q000627:therapeutic use*; D001743:Urinary Bladder / Q000187:drug effects*; D014550:Urinary Incontinence, Stress / Q000188:drug therapy*; D014563:Urodynamics / Q000187:drug effects
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; D014147:Tramadol; D009020:Morphine