Increased neuronal activity of micturition centers in mice model of cyclophosphamide-induced cystitis

Kim S J1, Han J Y2, Cho S T3, Kim S W4, Kim K H5

Research Type

Pure and Applied Science / Translational

Abstract Category

Pelvic Pain Syndromes

Abstract 770
Non Discussion Abstracts
Scientific Non Discussion Abstract Session 36
Painful Bladder Syndrome/Interstitial Cystitis (IC) Neuropathies: Central Animal Study
1. Department of Urology, Yonsei University Wonju College of Medicine, Wonju, Korea, 2. Department of Urology, Pusan National University Yangsan Hospital, Pusan, Korea, 3. Department of Urology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea, 4. Department of Urology, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea, 5. Department of Urology, Gachon University Gil Medical Center, Gachon University School of Medicine, Incheon, Korea
Links

Abstract

Hypothesis / aims of study 
Interstitial cystitis/bladder pain syndrome (IC/BPS) is regarded as pain conditions suggesting systemic involvement beyond the bladder and modulation of central nervous system (CNS) induced by chronic peripheral insult is introduced one of underlying mechanism of IC/BPS. However, little studies have been existed about change of CNS response to chronic peripheral insult in IC/BPS. Moreover, present IC/BPS animal models have limitation to represent how CNS is influenced by peripheral noxious stimuli. Therefore, we studied the change of CNS in mice model of cyclophosphamide (CYP)-induced cystitis that is one of the commonly used IC/BPS animal models.
Study design, materials and methods 
Adult mice were randomly divided into the following 2 groups (n = 10 in each group): control group and IC group. IC was induced by peritoneal injection with 80 mg/kg of cyclophosphamide. Cystometry was performed. Immunohistochemistry analysis was conducted to evaluated c-Fos and nerve growth factor (NGF) expression in the medial preoptic area (MPA), ventrolateral periaqueductal gray (vlPAG) and pontaine micturition center (PMC) were analyzed.
Results 
IC group showed significantly increased contraction pressure (CP) and decreased contraction interval (CI) compared with control group. Inflammatory cytokine (TNF-α, IL-1ß, IL-6) of the bladder was significantly increased in IC group compared with the control. Overexpression of c-Fos and NGF in MPA, vlPAG, and PMC of IC group was observed compared with control group.
Interpretation of results 
Cystometric findings and increased inflammation observed in the bladder of CYP-induced cystitis were appropriate for IC/BPS. Moreover, increased expression of c-Fos and NGF noted in MPA, vlPAG, and PMC meant neuronal activation of micturition centers. These results demonstrated that peripheral insult from the bladder induced neuronal activation of micturition centers in CYP-induced cystitis mice.
Concluding message 
Neuronal activation of micturition centers in CYP-induced cystitis is a finding to show that CNS can be influenced by the peripheral insult from the bladder. Therefore, we suggest that CYP-induced cystitis is an animal model to reflect the change of CNS noted in IC/BPS.
References 
  1. Am J Physiol Regul Integr Comp Physiol 2006;291:R692-R703.
  2. Int Neurourol J 2018;22(Suppl 1):S3-9.
Disclosures
Funding This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2015R1C1A1A02036452). Clinical Trial No Subjects Animal Species Mouse Ethics Committee Institutional Care and Use Committee of Kyung Hee University
26/04/2024 02:49:20