Interstitial cystitis/bladder painful syndrome (IC/BPS) is still an “enigma” due to its elusive etiology and lack of curative therapy. An innovative approach in the management of chronic pain is represented by alpha-lipoic acid (ALA), a naturally occurring disulphide compound and antioxidants. This study was designed to evaluate the efficacy of ALA (as add-on therapy) in the management of pain-resistant patients suffering from IC/BPS.

Female patients suffering from IC/BPS, poorly responsive to conventional pharmacological agents, were included in this exploratory study. Women were randomly assigned to receive convenctional therapy alone or associated to a commercially available ALA- 600 mg (Tiolide®; once daily). History, uro-gynaecological examination, the 3-day bladder diary and Visual Analogue Scale (VAS; 0=worse,10=best) to score pain intensity, were collected from patients’ clinical charts. Baseline evaluation was repeated at 3 and 6- mos follow- up.

Twenty-five IC/BPS patients were enrolled (mean±SD age: 39.6±6.7y.o.). Conventional therapy included poly-pharmacotherapies as amytryptiline, nimesulid, pregabalin, tapentadol. At baseline 34.7% of patients had bladder pain/burning (P/B) sensation, 30.4% had urethral P/B, 17.6% had dyspareunia and 13% of them had anal P/B. 20/25 (80%) subjects presented with urgency, 18/25 (72%) with increased day-time and night-time urinary frequency and 10/25 (40%) with urgency urinary incontinence (UUI). At 3 and 6-mos follow-up, urinary symptoms increased in both trial groups, with a greater effect seen with the addition of ALA (p< 0.01). The addition of ALA to treatment was also significantly associated with improvements in pain (p< 0.00), particularly in dyspareunia and pelvic floor muscle tone. 3 patients stopped assuming ALA due to lack of efficacy. At 6-mos follow-up, pain completely disappeared in 20% of patients (5/25), and substantially decrease in the remaining cases. No side effects have been recorded during ALA administration.

The results in the present study show that 86.7% of patients reported a large benefit in pain reduction with ALA as add-on therapy. There are 3 major lines of evidence supporting our results: ALA acts to reduce fractalkine mRNA (CX3CL1) and protein expression, a chemokine markedly increased in chronic cystitis. ALA could reverse the detrimental effects of high levels of oxidative stress in bladder inflamed tissue due to its antioxidant activity. Since bladder inflammation may significantly influence regulation of detrusor activity, we speculate that ALA could prevent bladder hyperreflexia induced by chronic bladder inflammation.

Our study provides preliminary evidence suggesting that ALA as add-on therapy to conventional pharmacological regimens in patients with IC/BPS contributes to a significant pain intensity reduction. Worth of noting, relief in pain was obtained in our patients without any consistent side effect. Future studies should be addressed to investigate the benefits of this pharmacological agent, used alone or in combination, in the treatment of patients with IC/BPS.