低能量體外震波抑制Capsaicin誘發攝護腺炎之疼痛與發炎
王弘仁, 莊燿吉
高雄長庚紀念醫院外科部 泌尿外科
Low energy shock wave therapy inhibits inflammatory moleculars and suppresses prostatic pain on capsaicin induced prostatitis model in rat
Hung-Jen Wang, Yao-Chi Chuang
Divisions of Urology, Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Purpose:
The low energy extracorporeal shock wave therapy (L-ESWT) has been proved to attenuate inflammatory condition and reduce pain in soft tissue. Recently, several studies demonstrate the low energy extracorporeal shock wave therapy significant improvement of pain, QoL, and voiding conditions in nonbacterial prostatitis /CPPS patient comparison to the placebo group. However, these studies were limited to clinical efficacy. The mechanism of ESWT on nonbacterial prostatitis /CPPS has not been studied. This is the first study focusing on the changes of inflammatory moleculars and pain behaviors in animal model. The aims of this study was to examine the pathological changes and immunoistochemical analysis in nonbacterial prostatitis rats with shock wave therapy.
Materials and Methods:
Capsaicin dissolved in a vehicle of 10% alcohol, 10% Tween 80 and 80% saline will be injected into the ventral lobes of the prostate at doses of vehicle only (sham control group) and 10 mM in 0.1 ml with a 30-gauge needle in each lobe. Control (capsaicin injection without shock wave) and various numbers of shock wave (100, 200 or 300 shocks) at the energy of 0.12 mJ/mm2 will be applied into the prostate of male SD rats right after capsaicin injection (N=16, 8 for each group). Three and seven days after L-ESWT, the prostate tissue will be harvested for histology, immunohistochemical study of COX-2, TNF-a in the prostate. The positive stained cells in four randomized 200x visual field in each animal were counted. Baseline animal behavior was recorded before surgery. Behavioral changes following shockwave therapy were then scored every 30 minutes for 3 times 2 hours after recovery from anesthesia. We used a scoring scale of 1 to 5 as previous reported. A minimum score of 1 was assigned if no parameter was affected compared with baseline behavior and maximum symptom severity was assigned the score of 5. Blinded observers performed all experiments and each experimenter scored 2 rats in parallel.
Results:
Capsaicin injection into prostate induced marked behaviour changes: including closing of the eyes and hypolocomotion. Capsaicin-induced pain behaviors were significantly decreased by LESW treatment. The eye open score increased in capsaicin group and significantly decreased after 100, 200 and 300 shockwave treatment (3.25±0.34; 1.92±0.37; 1.46±0.14; 1.37±0.12, respevtively, p< 0.05 n=8 each group). Locomotion socres in all groups were lower after shcok wave therapy compare with capsaicin group but not significant in 100 shock group (3.46±0.39; 3.00±0.13; 2.13±0.18; 1.75±0.20, p<0.05, n=8 each group). After capsaicin injection, inflammatory cells were accumulated in prostate which aslo showed significant higher COX-2 and TNF-alpha positive stain compared with vehicle injection. The capsaicin-induced prostate inflammation was dose dependently ameliorated by L-ESWT. Average COX-2 positive cell count in capsaicin, 100, 200 and 300 shockwave groups at day 3 was 16.33±1.87, 61±7.39, 25±4.19, 22.25±1.03, 27.5±1.94 repectively. The decrement was significant in 200, 300 shock wave group but not in 100 shock wave group in COX-2 expression ( p=0.002, 0.0046 and 0.757). The same result was also observed at day 7. The TNF-alpha cell count increased with time (6.08±1.00 for day 3 and for 26.78±8.36 day7). L-ESWT also decreased the TNF-alpha cells but was only significant at day 7 in both 200 and 300 shock wave group (p=0.028). L-ESWT decreased pain behaviour and reduce inflammation conditions in capsaicin injected prostate. The effect was dose dependent which was compatible between behaviour and inflammatory molecular expression. Energy intensity of 100 shock wave was not eough to redece inflammation condition. However, there was no difference between 200 and 300 shock waves in amelioration of pain and inflammation in capsaicin injected prostate.
Conclusion:
L-ESWT can deduce the inflammation condition and reduce the pain behaviour in the nonbacterial prostatitis rat model induced by Capsaicin injection.