Painful bladder syndrome/interstitial cystitis (PBS/IC) is a collective term covering a range of clinical complaints and pathological findings. Approximately 10-50% of PBS/IC patients demonstrate a classical mucosal ulcer (Hunner's ulcer), and the majority are diagnosed on the basis of positive factors and exclusions derived from the diagnostic criteria of the National Institute of Diabetes and Digestive and Kidney Diseases for IC [1, 2]. The etiology of PBS/IC includes a diversity of factors and remains poorly understood. Therefore, appropriate therapy has not been established from clinical evidence [3–5]. Hyperbaric oxygen (HBO) therapy has been reported to be effective in patients with cyclophosphamide-induced hemorrhagic cystitis and chronic radiation cystitis for approximately 20 years [6–9]. The pathological finding of chronic radiation cystitis is similar to PBS/IC, focusing on ischemia and a reduction in bladder capacity due to fibrosis of the bladder wall [10–12]. On the basis of these findings, a pilot study concerning HBO treatment in several PBS/IC patients whose symptoms had not been improved by other conventional treatments was carried out.

The mechanism of action underlying HBO treatment is attributed to hyper-saturation of the plasma with dissolved oxygen. This gives rise to an increased concentration gradient between the circulation and surrounding tissues, allowing oxygen to enter damaged hypoxic urothelial tissues. HBO treatment accelerates growth of healthy granulation in injured tissues via stimulation of leukocytic functions including phagocytosis and production of growth factors related to angiogenesis [13, 14]. HBO therapy has been used predominantly for chronic radiation cystitis and cyclophosphamide-induced hemorrhage cystitis in the last 20 years [6–9]. Chronic radiation cystitis is characterized by various histological alterations including sub-mucosal hemorrhage, interstitial fibrosis and smooth muscle fibrosis [10], which correspond to classical PBS/IC with ulcerative lesions [11, 15]. Therefore, it was hypothesized that HBO could be an effective treatment for PBS/IC with typical histological changes (glomerulations, Hunner's ulcer and interstitial fibrosis). Seven of 11 cases treated with HBO demonstrated a significant decrease in urinary frequency and pelvic pain and an increase in bladder capacity. Cystoscopic examination revealed the scarring or healing phase of ulcerative lesions in all responders. Furthermore, the positive effects on symptoms were sustained for a minimum of 12 months. Van Ophoven et al. carried out a pilot study concerning HBO in six PBS/IC patients [16]. Our group reported that HBO treatment resulted in a marked improvement of severe PBS/IC symptoms in the initial two cases [17]. In addition, van Ophoven's research group reported the effectiveness of HBO for PBS/IC on the basis of a randomized, double-blind, sham controlled clinical study [18]. This study revealed that the scale of pelvic pain in the HBO treatment group was significantly better than in the sham control group, and the amelioration in responders was sustained 12 months after HBO treatment. The results of our study are almost compatible with their report. Interestingly, secondary HBO treatment prolonged the period of remission in two cases (cases 1, 2). Therefore, it is likely that a repeated course of HBO could accelerate the healing phase of ulcerative PBS/IC disease. Three of the four cases that responded poorly to HBO presented with non-ulcerative PBS/IC. Thus, we speculate that ulcerative lesion with the most evident expression of bladder ischemia may be a predictive factor to result in good response to HBO. HBO therapy was well tolerated by patients; adverse events including visual disturbance, eustachian tube dysfunction and claustrophobia were unusual [19]. Furthermore, the advantage of HBO treatment over conventional therapies such as hydrodistension [15], intravesical instillation of dimethyl-sulfoxide (DMSO) [20] and intravesical submucosal injection of Botulinum toxin type A [21, 22] is that it is non-invasive.

The long-term efficacy of HBO treatment in 11 PBS/IC patients resistant to other conservative therapies was investigated. Seven of 11 patients, who underwent 10 or 20 sessions of HBO treatment, demonstrated good amelioration of the evaluated parameters including IC symptom score, scale for pain and urgency, 24-hour urinary frequency and bladder volume, for at least one year. Furthermore, two responders with worsening symptoms experienced prolonged improvement after additional HBO treatment sessions. HBO therapy was well tolerated, with few patients developing transient eustachian tube dysfunction and reversible exudative otitis media.

The present study suggests that HBO could be used for the treatment of PBS/IC patients resistant to various conventional therapies.