silodosin and Pain

Using a selective α-blocker for medical expulsive therapy (MET) is a cost-effective treatment approach widely used for ureteral stones.. To evaluate the efficacy of silodosin, a selective α-1a receptor antagonist, in this setting.. This was a multicenter, phase 2 study conducted in adult patients with a unilateral ureteral calculus of 4-10mm. Of 239 patients in the safety population, six discontinued due to adverse events.. Patients were randomized 1:1 to receive silodosin 8 mg or placebo for up to 4 wk.. The primary outcome was spontaneous stone passage, analyzed using logistic regression. Secondary outcomes included time to stone passage, emergency room (ER) visits, hospital admissions, analgesic use, and incidence and severity of pain.. No significant differences between the silodosin and placebo groups were observed for passage rate of all stones (52% vs 44%, respectively; p=0.2). However, silodosin achieved a significantly greater rate of distal ureter stone passage than placebo (p=0.01). Significant differences were not observed for ER visits, hospital admission, or use of analgesics. The number of patients in the intent-to-treat population was slightly below the calculated sample size (232 vs 240) and sample sizes were not calculated for subgroup analyses.. This is among the first prospective, randomized, multi-institutional trials to examine the efficacy of a selective α-1a antagonist as MET in patients with ureteral calculi and did not demonstrate a benefit to the entire ureter. However, silodosin was found to be well tolerated and beneficial in facilitating the passage of distal ureteral stones, warranting additional future studies on distal stone elimination.. In this report, we looked at the efficacy of silodosin for the treatment of ureteral stones. We found that silodosin increased passage of distal ureteral stones.

Topics: Adrenergic alpha-Antagonists; Adult; Analgesics; Double-Blind Method; Emergency Medical Services; Female; Hospital Administration; Humans; Indoles; Logistic Models; Male; Middle Aged; Pain; Treatment Outcome; Ureter; Ureteral Calculi

Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) remains an elusive disease with the cause for the pain unclear. BPS/IC patients present increased sympathetic activity and high levels of urinary noradrenaline. At the experimental level, it has been shown that chronic adrenergic stimulation produces pain and bladder changes through an alpha 1A adrenoceptor mediated mechanism. Water avoidance stress (WAS) in rodents reproduces signs of nociception and bladder changes seen in BPS/IC patients. In this study, we explore the possible role of alpha 1A adrenoceptor in bladder pain and morphological changes. WAS was induced in a group of female Wistar rats. A separate WAS group received 0.2 mg/kg day silodosin (WAS + S). Lower abdominal pain was determined by performing sensitivity to Von Frey filaments. Bladder reflex activity was determined by cystometry in anaesthetised animals. Urine was collected for noradrenaline quantification by HPLC. Bladders were harvested and stained with Haematoxylin-eosin (to analyse urothelial morphology and to determine the disruption of surface umbrella cells) or with Toluidine Blue 0.1% to analyse mast cell infiltration. WAS increased urinary noradrenaline level and bladder frequency and decreased mechanical pain threshold, which was reversed by silodosin. WAS induced lymphocytic and mast cells infiltration in the mucosa and mild urothelial disruption, which was absent in WAS + S group. Alpha 1A adrenoceptor stimulation has an important role in the appearance of bladder pain in rats. Since BPS/IC patients present high levels of noradrenaline, alpha 1A stimulation may be an additional trigger for bladder dysfunction presented by these patients. Further studies will determine the clinical relevance of this finding in the treatment of BPS/IC patients.

Topics: Adrenergic alpha-1 Receptor Antagonists; Animals; Avoidance Learning; Female; Indoles; Norepinephrine; Pain; Rats, Wistar; Receptors, Adrenergic, alpha-1; Stress, Psychological; Urinary Bladder; Water