To investigate the therapeutic effects of electroacupuncture (EA) on bladder dysfunction in a rat model of neurogenic bladder (NB) following spinal cord injury (SCI), and to explore its impact on the phosphorylation of connexin 43 (Cx43) via protein kinase A (PKA) signaling.
Fifty-six female Sprague-Dawley rats were randomly assigned to Sham, NB, EA, and EA + H-89 (PKA inhibitor) groups. A modified Hassan Shaker method was used to induce SCI. EA was applied at Ciliao (BL32), Zhongji (CV3), and Sanyinjiao (SP6) acupuncture points using sparse-dense wave stimulation with frequencies of 10 Hz/50 Hz and intensities of 1-3 mA for 7 days. Bladder function was assessed through urodynamic studies, and detrusor muscle contractility was evaluated via muscle strip contraction assays. Histological changes were examined using HE staining, while ultrastructural alterations were observed with transmission electron microscopy. Immunohistochemistry was performed to detect PKA, Cx43, c-Kit, and stem cell factor (SCF) expression levels, and Western blot analysis was utilized to quantify protein expression of PKA, phosphorylated Cx43 (p-Cx43), Cx43, c-Kit, and SCF.
Rats in the NB group exhibited significantly increased leak point pressure, maximal bladder capacity, and compliance (P < 0.001), along with enhanced detrusor muscle contractility (P < 0.01). Histopathological examination revealed structural disorganization and ultrastructural damage of the detrusor muscle. Notably, bladder tissues showed elevated expression of Cx43 and c-Kit (P < 0.01), reduced PKA expression, and increased SCF expression (P < 0.001). Protein analyses indicated decreased levels of PKA and p-Cx43, and increased levels of Cx43, c-Kit, and SCF (P < 0.001). EA treatment resulted in a significant reduction in maximal bladder capacity (P < 0.01), leak point pressure, and bladder compliance (P < 0.001), as well as a decrease in detrusor muscle contractility (P < 0.01, P < 0.05). Additionally, EA improved histopathological conditions and restored protein expression profiles, including upregulation of PKA and p-Cx43, and downregulation of Cx43, c-Kit, and SCF (P < 0.001, P < 0.01). Administration of the PKA inhibitor H-89 attenuated the beneficial effects of EA on bladder function, detrusor muscle activity, histological structure, and protein expression (P < 0.05, P < 0.01, P < 0.001).
EA may ameliorate bladder dysfunction post-SCI by activating the PKA signaling pathway, promoting Cx43 phosphorylation, reducing expression of Cx43, c-Kit, and SCF, and modulating detrusor muscle overactivity.
The journal of spinal cord medicine. 2026 Jun 04 [Epub ahead of print]
Roujun Liang, Kun Ai, Yue Zhuo, Shifeng Deng, Xiaojing Luo, Chuning Tian, Pei Wu, Hong Zhang, Ming Xu
College of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, People's Republic of China.