Beyond the urothelium: Interplay between autonomic nervous system and bladder inflammation in urinary tract infection, bladder pain syndrome with interstitial cystitis and neurogenic lower urinary tract dysfunction in spinal cord injury-ICI-RS 2023

Michel Wyndaele; Ana Charrua; François Hervé; Patrik Aronsson; Luke Grundy; Vik Khullar; Alan Wein; Paul Abrams; Francisco Cruz; Célia Duarte Cruz

doi:10.1002/nau.25310

Beyond the urothelium: Interplay between autonomic nervous system and bladder inflammation in urinary tract infection, bladder pain syndrome with interstitial cystitis and neurogenic lower urinary tract dysfunction in spinal cord injury-ICI-RS 2023

Neurourol Urodyn. 2023 Oct 25. doi: 10.1002/nau.25310. Online ahead of print.

Authors

Michel Wyndaele¹, Ana Charrua^{2

3}, François Hervé⁴, Patrik Aronsson⁵, Luke Grundy^{6

7

8}, Vik Khullar⁹, Alan Wein^{10

11}, Paul Abrams¹², Francisco Cruz^{3

13

14}, Célia Duarte Cruz^{2

3}

Affiliations

¹ Department of Urology, University Medical Center Utrecht, Utrecht, The Netherlands.
² Experimental Biology Unit, Department of Biomedicine, Faculty of Medicine of Porto, University of Porto, Porto, Portugal.
³ Translational Neurourology, Instituto de Investigação e Inovação em Saúde-i3S and IBMC University of Porto, Porto, Portugal.
⁴ Department of Urology, Ghent University Hospital, Ghent, Belgium.
⁵ Department Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁶ Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI), Flinders University, Bedford Park, Australia.
⁷ Hopwood Centre for Neurobiology, Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia.
⁸ Discipline of Medicine, University of Adelaide, Adelaide, Australia.
⁹ Department of Urogynaecology, St Mary's Hospital, Imperial College, London, UK.
¹⁰ Department of Surgery, Division of Urology, Perelman School of Medicine, Penn Medicine, University of Pennsylvania Philadelphia, Philadelphia, Pennsylvania, USA.
¹¹ Department of Urology, Desai Sethi Institute of Urology, Miller School of Medicine, University of Miami, Miami, Florida, USA.
¹² Bristol Urological Institute, North Bristol NHS Trust, Southmead Hospital, Bristol, UK.
¹³ Department of Surgery and Physiology, Faculty of Medicine of Porto, University of Porto, Porto, Portugal.
¹⁴ Department of Urology, Hospital São João, Porto, Portugal.

PMID: 37876314
DOI: 10.1002/nau.25310

Abstract

Introduction: Inflammation and neuronal hypersensitivity are reactive protective mechanisms after urothelial injury. In lower urinary tract dysfunctions (LUTD), such as urinary tract infection (UTI), bladder pain syndrome with interstitial cystitis (BPS/IC) and neurogenic LUTD after spinal cord injury (SCI), chronic inflammation can develop. It is unclear how the protective reactionary inflammation escalates into chronic disease in some patients.

Methods: During its 2023 meeting in Bristol, the International Consultation on Incontinence-Research Society (ICI-RS) reviewed the urothelial and inflammatory changes after UTI, BPS/IC and SCI. Potential factors contributing to the evolution into chronic disease were explored in a think-tank.

Results: Five topics were discussed. (1) Visceral fat metabolism participates in the systemic pro-inflammatory effect of noradrenalin in BPS/IC and SCI. Sympathetic nervous system-adipocyte-bladder crosstalk needs further investigation. (2) Sympathetic hyperactivity also potentiates immune depression in SCI and needs to be investigated in BPS/IC. Gabapentin and tumor necrosis factor-α are promising research targets. (3) The exact peripheral neurons involved in the integrative protective unit formed by nervous and immune systems need to be further identified. (4) Neurotransmitter changes in SCI and BPS/IC: Neurotransmitter crosstalk needs to be considered in identifying new therapeutic targets. (5) The change from eubiosis to dysbiosis in SCI can contribute to UTI susceptibility and needs to be unraveled.

Conclusions: The think-tank discussed whether visceral fat metabolism, immune depression through sympathetic hyperactivity, peripheral nerves and neurotransmitter crosstalk, and the change in microbiome could provide explanations in the heterogenic development of chronic inflammation in LUTD. High-priority research questions were identified.

Keywords: autonomic nervous system; bladder pain syndrome; inflammation; interstitial cystitis; spinal cord injury; urinary tract infection; urothelium.

Publication types

Review