The pathogenesis of bladder pain syndrome/interstitial cystitis (BPS/IC) is currently unclear. Scholars have put forward different hypotheses, including the function of the extracellular matrix surface of the glycosaminoglycan (GAG) layer, downregulation of tight junction protein, increased urothelial permeability, mast cell activation, neurogenic inflammation, and psychosomatic factors. The symptoms are very similar to severe bladder pain syndrome/interstitial cystitis, and the patients respond to existing medications. In 1956, Dr. George Hackett created a method for treating damaged ligaments and tendons called prolotherapy (proliferation therapy). Prolotherapy is defined as an alternative therapy for musculoskeletal and arthritic pain, including the treatment of irritating substances (such as dextrose, also known as d-glucose) injected into ligaments or tendons to promote the growth of new tissues. There are many clinical trials confirming that proliferation therapy can effectively treat painful musculoskeletal problems. For example, in patients with lateral epicondylitis treated with a solution with a final concentration of 10% dextrose, compared with patients treated with placebo (normal saline), pain and isometric muscle strength improved significantly. A recent literature review also tells that hypertonic glucose proliferation therapy can effectively treat a variety of musculoskeletal diseases.

Hence, this research suggests that dextrose prolotherapy is an affordable and effective pain management strategy in dealing with musculoskeletal neuroinflammation pain in BPS/IC. In order to begin to understand prolotherapy and its therapeutic utility, this study should begin to elucidate the immediate response of prolotherapy in the urology field by investigating the impact of dextrose.

This project is expected to accommodate subjects with BPS/IC, by injecting 10% dextrose into the bladder lining muscles of IC patients and performing various urodynamic tests and questionnaires to evaluate the patient's urinary voiding symptoms and urinary bladder function recovery. Afterward, the expressions of growth factors and cytokines in the urine samples were investigated in an attempt to reveal the mechanism of dextrose prolotherapy in BPS/IC disease.

This project treated 29 male and female subjects (aged over 20 years) with BPS/IC and other chronic inflammation of the bladder. The enrolled subjects were collected from May 2019 to October 2020. The subjects were given intravesical injections of 10% dextrose under intravenous general anesthesia in the operating room: 2 mL of 50% Dextrose (Vitagen Inj., Taiwan Biotech co. ltd., Taipei, Taiwan) was briefly diluted with 10 mL of normal saline and 11 sub urothelial injections (1 mL each site) were performed. The injection needle was inserted into the urothelium at the trigone (1 site), the posterior (6 sites), and the lateral walls (4 sites) of the bladder, using a 23-gauge needle under rigid cystoscopic injection instrument (22-Fr; Knittlingen, Richard Wolf, Germany). No post-injection analgesics were provided to patients. Treatment was repeated based on the patients' condition once every 2 weeks for the first 6 cycles and once every month for the remaining 3 cycles with a maximum of 9 planned therapy cycles up to 6 months. The patients would be followed-up and assessed at each treatment time and up to 1 month after the last treatment. 19 health subjects were also recruited as a healthy control as the comparison.

Inclusion Criteria:

1. The subject is aged over 20 years old.
2. The subject was diagnosed as bladder pain syndrome/interstitial cystitis subject with lower urinary tract symptoms, such as frequent urination, urgent urination, bladder pain, etc.

Exclusion Criteria:

1. The subject is aged under 20 years old.
2. Pregnant women.
3. The subject with congenital disorders of the urinary tract.
4. The subject with a urinary tract infection or tumor.