Mechanism of Capsazepine in alleviating pain in prostate-pelvic syndrome rats via TRPV1/CaMKⅡ/Synapsin-1 signaling pathway

AimTo investigate the effects of Capsazepine on pain in a rat model of prostate-pelvic syndrome (PPS) and to elucidate its underlying mechanisms.MethodsMale Sprague-Dawley (SD) rats were randomly assigned to either a sham group or a PPS model group. The PPS model was established by local carrageenan injection, with successful modeling confirmed by pain threshold assessment and histopathological evaluation of prostate tissue. Subsequently, PPS model rats were divided into a model group and a CPZ-treated group (n=9). The CPZ group received intraperitoneal injections of Capsazepine solution (2 mg·kg-1·d-1), while the sham and model groups received equivalent volumes of vehicle for 7 consecutive days. Mechanical and thermal pain thresholds were measured, and the prostate index was calculated. Histopathological changes in prostate tissue were examined using hematoxylin-eosin (HE) staining. Serum levels of substance P (SP) and calcitonin gene-related peptide (CGRP) were quantified by ELISA. Calcium ion concentration in dorsal root ganglia was measured, and protein expression levels of c-Fos, TRPV1, calmodulin (CaM), CaMKⅡ, phosphorylated CaMKⅡ (p-CaMKⅡ), synapsin-1, and phosphorylated synapsin-1 (p-synapsin-1) in DRG were analyzed by Western blotting.ResultsSeven days post-modeling, PPS model rats exhibited pain hypersensitivity and inflammatory cell infiltration in the prostate, consistent with PPS characteristics, confirming successful model establishment. After 7 days of treatment, Capsazepine significantly elevated pain thresholds, effectively attenuated histopathological damage in prostate tissue, and markedly reduced serum levels of SP and CGRP, along with calcium ion concentration in DRG. Furthermore, CPZ downregulated expression of TRPV1 and its downstream proteins.ConclusionCapsazepine alleviates PPS-associated pain by inhibiting activation of the TRPV1/CaMKⅡ/Synapsin-1 signaling pathway, thereby reducing the release of pain mediators SP and CGRP.