Cold stress induces lower urinary tract symptoms

Authors

  • Tetsuya Imamura,

    Corresponding author
    • Department of Lower Urinary Tract Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
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  • Osamu Ishizuka,

    1. Department of Lower Urinary Tract Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
    2. Department of Urology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
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  • Osamu Nishizawa

    1. Department of Lower Urinary Tract Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
    2. Department of Urology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
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Correspondence: Tetsuya Imamura Ph.D., Department of Lower Urinary Tract Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. Email: imatetu@shinshu-u.ac.jp

Abstract

Cold stress as a result of whole-body cooling at low environmental temperatures exacerbates lower urinary tract symptoms, such as urinary urgency, nocturia and residual urine. We established a model system using healthy conscious rats to explore the mechanisms of cold stress-induced detrusor overactivity. In this review, we summarize the basic findings shown by this model. Rats that were quickly transferred from room temperature (27 ± 2°C) to low temperature (4 ± 2°C) showed detrusor overactivity including increased basal pressure and decreased voiding interval, micturition volume, and bladder capacity. The cold stress-induced detrusor overactivity is mediated through a resiniferatoxin-sensitve C-fiber sensory nerve pathway involving α1-adrenergic receptors. Transient receptor potential melastatin 8 channels, which are sensitive to thermal changes below 25–28°C, also play an important role in mediating the cold stress responses. Additionally, the sympathetic nervous system is associated with transient hypertension and decreases of skin surface temperature that are closely correlated with the detrusor overactivity. With this cold stress model, we showed that α1-adrenergic receptor antagonists have the potential to treat cold stress-exacerbated lower urinary tract symptoms. In addition, we showed that traditional Japanese herbal mixtures composed of Hachimijiogan act, in part, by increasing skin temperature and reducing the number of cold sensitive transient receptor potential melastatin channels in the skin. The effects of herbal mixtures have the potential to treat and/or prevent the exacerbation of lower urinary tract symptoms by providing resistance to the cold stress responses. Our model provides new opportunities for utilizing animal disease models with altered lower urinary tract functions to explore the effects of novel therapeutic drugs.

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