PURPOSE: To study if cold stress-induced detrusor overactivity in ovariectomized rats is associated with increased thermosensitive transient receptor potential melastatin 8 (TRPM8) channel expression in the skin, and if the response can be inhibited by alpha1-adrenergic receptor blockade.
MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats at postnatal week 30 were randomly selected for ovariectomy (OVX, n=16) or sham ovariectomy (n=8). Five weeks later, cystometric measurements of the conscious, free-moving rats were performed at room temperature (RT, 28 ± 2ºC) for 20 min. Eight OVX rats were intravenously administered 1.0 mg/kg naftopidil, and the other OVX and sham-operated rats (n=8 each) were given naftopidil-free vehicle. Five min later, they were transferred to a low temperature (LT) environment (4 ± 2ºC) and micturition patterns were again recorded. TRPM8 channel expression in lumbar skin was estimated by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry.
RESULTS: TRPM8 channel mRNA and protein in the skin of OVX rats were significantly higher than in sham-operated rats. At RT, micturition parameters were similar for sham-operated and OVX rats. At LT, both sham-operated and OVX rats exhibited cold stress-induced detrusor overactivity, but the increased micturition frequency and decreased bladder capacity were significantly greater for OVX rats. Treatment of OVX rats with naftopidil inhibited the cold stress-induced detrusor overactivity.
CONCLUSION: Cold stress-induced detrusor overactivity in rats with decreased estrogen is associated with an upregulation TRPM8 channels in the skin, and is mediated by nerve pathways utilizing alpha1-adrenergic receptors.
Written by:
Noguchi W, Ishizuka O, Imamura T, Kurizaki Y, Yamagishi T, Yokoyama H, Lei Z, Silwal SG, Nishizawa O, Andersson KE. Are you the author?
Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan.
Reference: J Urol. 2012 Oct 12. pii: S0022-5347(12)05195-6.
doi: 10.1016/j.juro.2012.10.014
PubMed Abstract
PMID: 23069383
UroToday.com Investigative Urology Section
