以背根神經節為標的之低能量體外震波治療抑制大鼠非菌性慢性攝護腺炎的疼痛介質與中樞致敏化

張賀翔¹、莊燿吉^1,2、王弘仁^1,2

高雄長庚紀念醫院泌尿科

高雄長庚紀念醫院震波醫學與組織再造科研究中心

Low Intensity Extracorporeal Shockwave Targeting at Dorsal Root Ganglion Attenuate Nociceptive Markers and BOLD activity in a Rat Model of Nonbacterial Chronic Prostatitis

Ho-Hsiang Chang¹, Yao-Chi Chuang^1,2, Hung-Jen Wang^1,2
Department of Urology, Kaohsiung Chang Gung Memorial Hospital, Taiwan¹

The Center of Excellence in Shockwave Medicine and Tissue Regeneration², Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan²
 

Purpose: To assess whether low intensity extracorporeal shockwave(LESW) targeting at L6 Dorsal root ganglion (DRG) might have a central effect and reduce prostate pain and DRG inflammation.

Materials and Methods: For molecular experiments, the rats received ESWT immediate and 24 hours after capsaicin injection. For BOLD fMRI experiments, all the rats received fMRI image acquisition one day before capsaicin injection. One day after intraprostatic capsaicin or vehicle injection, the rats received 2nd fMRI scan. Li-ESWT group received two times of treatment right after and 24 hours after 2nd image acquisition. Three days after capsaicin injection the 3rd time fMRI scan was conducted.

Results: Co-localization of Trk-A and TrK-B immunofluorescence staining in prostate on day three and day 7 after intraprostatic capsaicin (CAP) injection. Double immunostaining showed that Trk-A immunoreactivity (red staining) was co-localized with TrK-B (green staining). Intraprostatic capsaicin (CAP) injection induced increment of Trk-A and Trk-B immunoreactivity in in prostate only on day 7, and this effect was ameliorated by 200 shocks of Li-ESWT. Western blot for detecting COX-2, TRPV-1, NGF, Trk-A, BDNF, Trk-B and CALCA expression in the L6 DRG on day three and day seven after intraprostatic capsaicin injection. All inflammatory molecules, neurogenic growth factors and receptors were upregulation on day three and day seven. Li-ESWT directly on DRG significantly suppressed COX-2, TRPV-1, NGF, Trk-A, BDNF, Trk-B and CALCA expression. (* p< 0.05; # p< 0.01; † p< 0.001) BOLD fMRI signal changes over time with or without Li-ESWT in capsaicin induced prostatitis rats. Shown here are activation maps of BOLD signal changes in ROI includes caudate putamen; lateral PAG and thalamus. One day after capsaicin injection, positive BOLD signal changes in-creased in caudate putamen, lateral PAG and thalamus. Li-ESWT did not showed any therapeutic effects on the BOLD signal. However, by day 3, Li-ESWT decreased the number of active voxels in these three pain-related ROI was significantly decrease. In rats without having Li-ESWT, the active voxels in caudate putamen and thalamus continue to increase by day 3. (* p< 0.05; # p< 0.01; † p< 0.001)

Conclusions: In the result we found the Li-ESWT on L6 DRG can transduced the signal downward to the prostate, which decreased the expression of COX-2, NGF and IL-6. We can also find that the NGF, BDNF receptors Trk-A and Trk-B was down regulated by ESWT on the L6- DRG. The shockwave on the dorsal root ganglion do modulate the inflammatory molecules and neurotransmitters DRG and related dorsal horn. These effects influence the brain activities in the pain related cortex areas. Li-ESWT targeted on the DRG decreased the TRPV1 expression in both peripheral and central neural pathways and induced changes in the brain activity in pain-related areas, which findings were coinciding with previous studies, and further confirming that Li-ESWT could modulate the brain pain circuits.