SUFU 2019: Ceftriaxone Inhibits Stress-Induced Hyperalgesia and Alters Cerebral Micturition and Nociceptive Circuits: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Study

Miami, FL (UroToday.com) Dr. Rodriguez and associates examined the effects of ceftriaxone (CEF)-dependent upregulation of the glutamate transport on the central amplification of stress-induced bladder hyperalgesia. They used adult, female Wistar-Kyoto rats were exposed to WAS (1 hr/d x 10 d) or sham paradigms following the daily administration of CEF or vehicle. On day 11, cystometrograms were obtained during titrated bladder dilation, with visceromotor responses (VMR) recorded simultaneously. Functional brain activation was assessed during passive bladder distension (20-cmH2O) following i.v. administration of [14C]-iodoantipyrine. Regional cerebral blood flow was quantified by autoradiography and analyzed in 3D reconstructed brains with statistical parametric mapping.

They found that rats, elicited visceral hypersensitivity during bladder filling as demonstrated by a decreased pressure threshold and visceromotor threshold triggering the voiding phase, as well as by increased VMR to bladder distension. Perfusion mapping revealed stress effects in brain regions noted to be responsive to passive bladder filling. Administration of CEF diminished visceral hypersensitivity and attenuated many of the stress-related functional brain changes within the supraspinal micturition circuit. A significant differential effect of CEF on the brains of stressed rats compared to controls was noted in posterior cingulate/anterior retrosplenial and primary somatosensory cortices. These regions contribute to nociceptive and to micturition circuits, show stress effects, and have been previously reported to demonstrate altered functionality in IC/BPS patients.

At the end, they concluded that the actions of CEF on the glutamate transporter, such might suggest the possibility of glutamatergic pharmacologic strategies in modulating stress-related centrally mediated bladder dysfunction.

Presented by: Larissa Rodriguez, MD, Associate Professor for Faculty and Student Initiatives and Professor of Urology, Keck School of Medicine of USC, Department of Urology, University of Southern California

Co-Authors: Daniel P. Holschneider, MD², Zhuo Wang¹, HH Chang², Rong Zang, Ph.D., DDS, ², Yuxing Guo, MD¹
Author Affiliation:
1. Keck School of Medicine of USC, USC Departments of Psychiatry and Behavioral Sciences, University of Southern California
2. Keck School of Medicine of USC, Department of Urology, University of Southern California

Written by: Bilal Farhan, MD, Clinical Instructor, Female Urology and Voiding Dysfunction, Department of Urology, University of California, Irvine @Bilalfarhan79 at the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction Winter Meeting, SUFU 2019, February 26 - March 2, 2019, Miami, Florida

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