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Peer-reviewedCC BYContinence

A pilot study on the impact of age on pain induced by Water Avoidance Stress in female and male Wistar Han rats

  • Lisa Pereira1
  • Mariana Santos-Pereira1
  • Liliana Santos-Leite2
  • Jane Meijlink3
  • Rolf-Detlef Treede4
  • Katy Vincent5
  • Jens Nagel6
  • Susana Maria Silva7
  • Francisco Cruz8
  • Ana Charrua
8 affiliations
  1. 1Departamento de Biomedicina - Unidade de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
  2. 2Departamento de Recursos Comuns, Centro de Recursos Animais, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
  3. 3International Painful Bladder Foundation, Naarden, Netherlands
  4. 4Heidelberg University, Mannheim, Germany
  5. 5Nuffield Department of Women's and Reproductive Health, John Radcliffe Hospital, University of Oxford, Oxford, UK
  6. 6Bayer AG, Research & Development, Pharmaceuticals, Wuppertal, Germany; Merz Therapeutics GmbH, Research & Development, Nonclinical Sciences, Frankfurt Main, Germany
  7. 7RISE-Health, Faculdade de Medicina, Universidade do Porto, Alameda Prof, Hernâni Monteiro, Porto, 4200-319, Portugal; Unidade de Anatomia, Departamento de Biomedicina, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
  8. 8RISE-Health, Faculdade de Medicina, Universidade do Porto, Alameda Prof, Hernâni Monteiro, Porto, 4200-319, Portugal; I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Serviço de Urologia, Centro Hospitalar São João, Porto, Portugal
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Abstract

Background and objective: Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a condition that changes with age. Integrating age as a biological variable in preclinical models is critical for translational validity. This study investigated whether aging modulates pain and bladder activity in a rat model of pelvic pain induced by Water Avoidance Stress (WAS). Methods: Thirty Wistar Han rats (females: 6-7, 15-18, 23-25 months; males: 6-7, 23-25 months) were randomized into age- and sex-specific groups. Females with 15-18 months underwent ovariectomy. Animals were exposed to WAS (1 h/day for 10 days) and assessed at baseline and post-WAS. Ongoing and evoked pain were evaluated using the Rat Grimace Scale, mechanical thresholds (Von Frey), and thermal sensitivity (Hargreaves) at the genital/thigh and hind paw. Spontaneous bladder activity was assessed using the Voiding Spot Assay. Effect size (Hedges’ g z ) and confidence interval (CI) were calculated, alongside paired comparisons. Key findings and limitations: Younger animals exhibited pain-like behaviors and genital/thigh sensitization, whereas old animals presented heterogeneous or minimal responses. VSA findings suggested an increase in low-volume spots in younger groups. Conclusions: and Clinical Implications: Genital/thigh's mechanical hypersensitivity indicates bladder-related pain mechanisms in the WAS model. Older rats exhibited fewer signs of pain in the WAS paradigm than younger rats. Findings support the need to refine age-inclusive models and improve bladder-specific behavioral metrics.

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Cite

BibTeXRIS
BibTeX
@article{pereira2026pilot,
  title = {{A pilot study on the impact of age on pain induced by Water Avoidance Stress in female and male Wistar Han rats}},
  author = {Lisa Pereira and Mariana Santos-Pereira and Liliana Santos-Leite and Jane Meijlink and Rolf-Detlef Treede and Katy Vincent and Jens Nagel and Susana Maria Silva and Francisco Cruz and Ana Charrua},
  journal = {Continence},
  year = {2026},
  month = oct,
  doi = {10.1016/j.cont.2026.102914},
  url = {https://doi.org/10.1016/j.cont.2026.102914},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - A pilot study on the impact of age on pain induced by Water Avoidance Stress in female and male Wistar Han rats
AU  - Lisa Pereira
AU  - Mariana Santos-Pereira
AU  - Liliana Santos-Leite
AU  - Jane Meijlink
AU  - Rolf-Detlef Treede
AU  - Katy Vincent
AU  - Jens Nagel
AU  - Susana Maria Silva
AU  - Francisco Cruz
AU  - Ana Charrua
PY  - 2026
DA  - 2026/10/30
JO  - Continence
DO  - 10.1016/j.cont.2026.102914
UR  - https://doi.org/10.1016/j.cont.2026.102914
AB  - Background and objective: Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a condition that changes with age. Integrating age as a biological variable in preclinical models is critical for translational validity. This study investigated whether aging modulates pain and bladder activity in a rat model of pelvic pain induced by Water Avoidance Stress (WAS). Methods: Thirty Wistar Han rats (females: 6-7, 15-18, 23-25 months; males: 6-7, 23-25 months) were randomized into age- and sex-specific groups. Females with 15-18 months underwent ovariectomy. Animals were exposed to WAS (1 h/day for 10 days) and assessed at baseline and post-WAS. Ongoing and evoked pain were evaluated using the Rat Grimace Scale, mechanical thresholds (Von Frey), and thermal sensitivity (Hargreaves) at the genital/thigh and hind paw. Spontaneous bladder activity was assessed using the Voiding Spot Assay. Effect size (Hedges’ g z ) and confidence interval (CI) were calculated, alongside paired comparisons. Key findings and limitations: Younger animals exhibited pain-like behaviors and genital/thigh sensitization, whereas old animals presented heterogeneous or minimal responses. VSA findings suggested an increase in low-volume spots in younger groups. Conclusions: and Clinical Implications: Genital/thigh's mechanical hypersensitivity indicates bladder-related pain mechanisms in the WAS model. Older rats exhibited fewer signs of pain in the WAS paradigm than younger rats. Findings support the need to refine age-inclusive models and improve bladder-specific behavioral metrics.
SN  - 2772-9737
ER  -