흰쥐에서 Capsaicin이 전립샘의 감각신경에 미치는 영향

Abstract

Prostatodynia is a common and chronic debilitating disease manifested by pain referable to the prostate such as perineal, inguinal, lower back, and suprapubic pain. It has been estimated that more than half of all men suffer from this entity sometime in their lives. Although infection, autoimmunity, and intraprostatic reflux are some of the candidates for its cause, the etiology and pathogenesis of prostatodynia remains unclear. This study investigated the effect of capsaicin, a selective nociception blocking agent, on the prostatic afferent, and determined the presence of capsaicin sensitive nerve fiber at the rat prostate. Adult male Sprague-Dawley rats were used for the experiment. Capsaicin (4mM) or vehicle (10% ethanol, 10% Tween 80, 80% normal saline) 0.125 ml each was injected directly into the right ventral prostate and sacrificed at 1, 2, 24 hours, 1 week and 1 month after injection. Five rats were sacrificed at each time interval. Calcitonin gene related peptide (CGRP) and neurofilament (NF) immunohistochemistry was performed at the L2 dorsal root ganglion (DRG). CGRP and substance P (SP) immunohistochemistry was performed at L2 and T8 dorsal horn, and the prostate. The change in the number of c-fos positive cells was determined at L2, L6, and T8 dorsal horn. Change in c-fos positive cells was also compared between those injected with xylene only and those injected with xylene 24 hours and 1 week after capsaicin pretreatment. The prostate was observed under hematoxylin-eosin (H-E) staining for histological change after capsaicin injection. The number of CGRP positive cells decreased nearly half at the L2 DRG 24 hours after capsaicin injection and remained decreased up until 1 month. However, the number of NF positive cells did not change suggesting the effect of capsaicin only on B-type neurons. Decrease in CGRP and SP at the dorsal horn was observed only at L2 after capsaicin injection. There was no change at T8 and after vehicle injection. The number of c-fos positive cells after capsaicin and vehicle injection reached a peak at 2 hours at L2 and at 2 and 1 hour, respectively, at L6. However, c-fos positive cell was not observed at T8 even after capsaicin injection. In animals pretreated with capsaicin, injection of xylene induced fewer c-fos positive cells at both L2 and L6 compared to animals injected with xylene only. H-E staining of the prostate did not reveal any significant histological change of the prostate after capsaicin injection. However, CGRP and SP positive nerve fibers was not observed 1 week after capsaicin treatment. Direct injection of capsaicin into the rat prostate induced depletion of CGRP and SP, neurotransmitters related to pain conduction, at the DRG, dorsal horn and prostate suggesting that the prostatic afferent is affected by capsaicin. The decreased c-fos positive cells observed after capsaicin pretreatment further supports this observation and demonstrates that capsaicin injection can desensitize nociception originating from the rat prostate.