Investigations of urethral sphincter activity in mice with bladder hyperalgesia before and after drug administration of gabapentin
This study investigated the effect of gabapentin on lower urinary tract dysfunction focusing on urethral activities and cystitis-induced hyperalgesia in a mouse model of painful bladder syndrome/interstitial cystitis (PBS/IC). The electromyography (EMG) of external urethral sphincter (EUS) was difficult to obtain, but contained useful information to examine the drug effect in mice.
Female C57BL/6J mice were intraperitoneally (ip) administration with either saline or 200 mg/kg of cyclophosphamide (CYP) 48 h before experimental evaluation. Cystitis mice were treated with administration of gabapentin (25 or 50 mg/kg, ip). Cystometry and EUS EMG were obtained and analyzed during continuous bladder infusion. The visceral pain-related visceromotor reflex (VMR) was recorded in response to isotonic bladder distension.
Cystitis mice showed shorter inter-contraction intervals and increased occurrence of non-voiding contractions during bladder infusion, with increased VMR during isotonic bladder distension, indicating cystitis-induced bladder hyperalgesia. Gabapentin (50 mg/kg) suppressed effects of CYP on cystometry, but not on EUS EMG activity, during bladder infusion. The effect on urodynamic recordings lasted 4 h. VMR was significantly reduced by gabapentin.
The present study showed that CYP-induced cystitis in mice is a model of visceral hyperalgesia affecting detrusor contractions, not urethral activations. The technique of using EUS EMG to evaluate the drug effects on urethral activities is novel and useful for future investigations. Gabapentin can be as a potential treatment for detrusor overactivity and PBS/IC.
KeywordsExternal urethral sphincter Electromyography Cyclophosphamide Visceral pain
The authors thank Jackie Mao for technical assistance at Urology, University of Southern California, CA, USA. The authors also thank Dr. Mitsuharu Yoshiyama at Urology, University of Yamanashi Graduate School of Medical Sciences, Japan for detailed instructions to obtain EUS EMG in mice.
The study was supported by IUGA basic science Grant to Ghoniem, and by NIH (DK106181) to Chang.
Compliance with ethical standards
Conflict of interest
All the authors declare that they have no conflict of interest.
The “Principles of laboratory animal care” (NIH publication No. 86-23, revised 1985) were followed. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
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