Effects of Low Intensity Extracorporeal Shockwave Therapy on Inflammatory Mediators and Central Sensitization on Capsaicin Induced Nonbacterial Prostatitis Model in Rats

Wang H1, Chuang Y1, Chen Y2

Research Type

Basic Science / Translational

Abstract Category

Pelvic Pain Syndromes / Sexual Dysfunction

Abstract 459
Basic Science: Overactive Bladder and Pain
Scientific Podium Short Oral Session 24
Thursday 30th August 2018
14:30 - 14:37
Hall C
Pain, Pelvic/Perineal Animal Study Basic Science
1. Department of Urology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, 2. The Center of Excellence in Shockwave Medicine and Tissue Regeneration, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan

Hung-Jen Wang



Hypothesis / aims of study
Low energy shock wave therapy (LESWT) has been suggested to attenuate inflammatory condition and reduce somatic pain. Recently, several studies demonstrate that LESWT significantly improve pain, QoL, and voiding conditions in patients with nonbacterial prostatitis /CPPS comparison to the placebo treated group. Previously We demonstrated that intra-prostatic capsaicin injection activates COX2, NGF and other inflammatory mediator expression in the prostate and induces prostatic pain. Low energy ESWT could inhibit the capsaicin induced inflammation and reduce prostatic pain in a dose dependent fashion (2017 ICS Florence). In clinical practice, we observe some patients with prostatitis also induced voiding dysfunction and unstable bowel habits, however, the mechanisms remained unclear. It has been suggested that persistent afferent (sensory) input from affected organs is important to the maintenance of pain and hypersensitivity. Central sensitization might lead to persist pain even the inflammatory condition in primary organ is subsided. We hypothesize that L-ESWT might attenuate the NGF(nerve growth factor) and related neurotrophin and inflammasone expression in spinal cord level.
Study design, materials and methods
All experimental procedures were performed in accordance with institutional guidelines and approved Institutional Animal Care and Use Committee before the study. Adult male S.D. rats were injected with vehicle or capsaicin (10 mM, 0.1 cc) into the prostate. Right after injection, various numbers of shock wave (0, 100, 200 or 300 shocks; 0.12 mJ/mm2) were applied into the prostate. Three days after LESWT, the L6 and S1 spinal cord and dorsal root ganglion(DRG) at the level of L6 spinal were removed for histology, COX-2, NGF, BDNF (brain-derived neurotrophic factor) expression by using immunohistochemical staining. Western blot analysis was used to determine the relative protein expressions. The prostate and L6 and S1 spinal cord were removed three days after shock wave therapy for western blot analysis of NGF, BDNF, TRPV1 and COX-2 expression.
Capsaicin injection into prostate induced inflammatory cells accumulation in L6 level dorsal root ganglion but not L6 or S1 spinal cord. Significant increase in the number of Cox-2, NGF and BDNF-immunoreactive (IR) cells in the L6 DRG compared with vehicle injection (Fig.1).  The capsaicin-induced dorsal root gandlion inflammation was dose dependently ameliorated by LESWT. On day 3 LESWT decreased COX-2(+) cell accumulation in 100, 200 and 300 shockwave groups (21.3%, 58.7%, and 21.4% reductions, repectively) (Fig. 1). The decrement was significant in 200 shock wave group but not in 100 and 300 shock wave group. The neurotrophin IR cells in L6 DRG increased with time (372% for NGF and 434% for BDNF, Fig 1). LESWT also decreased the neurotrophin IR cells (NGF, 30.2%, 65.2%, and 25.3% reductions; BDNF 102%, 55.9% and 17.8% reductions, respectively in 100, 200 and 300 shockwave groups)but was mostly significant in 200 and 300 shock wave group (p=0.001). In western blot analysis, LESWT could also downregulate expression of NGF, BDNF, TRPV1 and COX-2 expression, which was identical to the immunohistochemical finding. (Fig.2)
Interpretation of results
The capsaicin induced prostatitis model can also increase COX-2 produced by the inflammatory responses in the dorsal root ganglion tissues and affect the production of NGF and BDNF in DRG. The effect of LESWT on prostate could not only decrease prostatic inflammation but also have effect on referred central nerve system in a dose dependent fasion, which showed less significant effect at the dose of100 shock waves, but more promising at the dose of 200 and 300 shock waves.
Concluding message
Intraprostatic capsaicin injection activates COX2, NGF and related inflammasone expression in the L6 level dorsal root ganglion. LESWT at prostate could also inhibit the capsaicin induced COX-2 and modulate neurotrophin expression at central nervous systems in a dose dependent fashion. This finding suggests a potential clinical benefit of LESWT at the optimal dose for ameliorate chronic pain and its associated central sensitization.
Figure 1
Figure 2
  1. Wang H-J, Lee W-C, Tyagi P, Huang C-C, Chuang Y-C. Effects of low energy shock wave therapy on inflammatory moleculars, bladder pain, and bladder function in a rat cystitis model. Neurourology and Urodynamics. 2017;36: 1440–1447. https://doi.org/10.1002/nau.23141
Funding Kaohsiung Chang Gung Memorial Hospital (CMRPG8F1591) and Ministry of Science and Technology Clinical Trial No Subjects Animal Species Rat Ethics Committee Kaohsiung Chang Gung Memorial Hospital Institutional Animal Care and Use Committee