Epirubicin (EPI) is commonly used as an adjuvant intravesical therapy for treatment of non-muscle invasive bladder cancer (NMIBC). However, Its frequent instillation is mainly complicated with cystitis. Low energy shock wave (LESW) has been shown to have both anti-inflammatory and analgesic effects, so we evaluated the effect of LESW on the bladder inflammatory changes associated with EPI-induced cystitis in a rat model.

30 female Fischer rats were randomly allocated into 3 groups (10 rats each); Control, EPI and EPI plus LESW groups. Saline (0.6 ml) or EPI (0.6 mg/0.3 ml diluted in saline) was instilled and retained in the bladder for 1 hour, LESW treatment (300 pulses, 0.12 mJ/mm²) was applied simultaneously to the bladders in EPI plus LESW group. This was repeated daily for 1 week. Behavioral assessment of pain, eye movement and locomotion was performed 1 hour after instillation. Magnetic resonance imaging (MRI) was also carried out to estimate bladder wall thickness and bladder capacity. After sacrification, bladders were harvested for bladder weight estimation and histopathological examination. Molecular studies of inflammatory markers in terms of IL-6 and TNF-α relative gene expression levels were also assessed.

LESW treatment significantly improved pain, eye movement and locomotion scores, reduced bladder weights and down-regulated IL-6 and TNF-α relative gene expression levels (table 1). MRI of EPI plus LESW group showed that bladder wall thickness was 0.73 ± 0.25 mm vs. 1.64 ± 0.27 mm in EPI group (p <0.001) and bladder capacity was 8.7 ± 1.53 µl vs. 5.07 ± 1.31 µl in EPI group (p <0.001). Yet, there was no significant difference regarding the degree of bladder inflammation between EPI and EPI plus LESW groups (table 2).

Intravesical instillation of EPI up-regulated IL-6 and TNF-α expression and induced bladder inflammation, thus caused pain behavioral changes, increased bladder wall thickness and reduced bladder capacity. LESW treatment has been shown to suppress the inflammatory changes associated with intravesical EPI instillation, by significant down-regulation of IL-6 and TNF-α relative gene expression. It also resulted in significant improvement of pain behavioral changes. EPI plus LESW group showed statistically significant lower bladder weights, less bladder wall thickness and increased bladder capacity relative to EPI group, but the degree of bladder inflammation didn't differ significantly between both groups.

LESW suppresses the bladder inflammatory changes induced by intravesical instillation of EPI, so LESW might be nominated as a promising method for relieving bladder inflammation associated with EPI instillation for treatment of NMIBC.