Moxibustion attenuates neurogenic detrusor overactivity in spinal cord injury rats by inhibiting M2/ATP/P2X3 pathway.

PURPOSE: Activation of muscarinic receptors located in bladder sensory pathways is generally considered to be the primary contributor for driving the pathogenesis of neurogenic detrusor overactivity following spinal cord injury. The present study is undertaken to examine whether moxibustion improves neurogenic detrusor overactivity via modulating the abnormal muscarinic receptor pathway. MATERIALS AND METHODS: Female Sprague-Dawley rats were subjected to spinal cord injury with T9-10 spinal cord transection. Fourteen days later, animals were received moxibustion treatment for one week. Urodynamic parameters and pelvic afferents discharge were measured. Adenosine triphosphate (ATP) content in the voided cystometry fluid was determined. Expressions of M2, M3, and P2X3 receptors in the bladder mucosa were evaluated. RESULTS: Moxibustion treatment prevented the development of detrusor overactivity in spinal cord injury rats, with an increase in the intercontraction interval and micturition pressure threshold and a decrease in afferent activity during filling. The expression of M2 was markedly suppressed by moxibustion, accompanied by a reduction in the levels of ATP and P2X3. M2 receptor antagonist methoctramine hemihydrate had similar effects to moxibustion on bladder function and afferent activity, while the M2-preferential agonist oxotremorine methiodide abolished the beneficial effects of moxibustion. CONCLUSION: Moxibustion is a potential candidate for treating neurogenic bladder overactivity in a rat model of spinal cord injury, possibly through inhibiting the M2/ATP/P2X3 pathway.

Electroacupuncture improves neurogenic bladder dysfunction through activation of NGF/TrkA signaling in a rat model.

OBJECTIVE: To observe the effect of electroacupuncture on the morphological change of the bladder tissue and the protein expression levels of NGF, TrkA, p-TrkA, AKT, and p-AKT in the bladder tissue of rats with neurogenic bladder after suprasacral spinal cord injury and to preliminarily explore its partial mechanism of action. METHODS: Eighty female Sprague-Dawley rats were randomly divided into blank group, model group, electroacupuncture group, model/siNGF group, and electroacupuncture/siNGF group according to random number table method with 16 rats in each group. Eighty Neurogenic bladder models after suprasacral spinal cord injury were established by adopting a modified spinal cord transection method. Electroacupuncture intervention was conducted on the 19th day after modeling. The bladder function was detected by bladder weight, urine output, serum BUN, and urine protein. After treatment for 7 consecutive days, the rats were killed and the bladder tissues were removed rapidly for microscopic observation of morphological change after hematoxylin and eosin stain and for determination of the protein expression levels of NGF, TrkA, p-TrkA, AKT, and p-AKT via Western blot analysis. The transcription of NGF was measured by reverse-transcription polymerase chain reaction. RESULTS: After treatment, compared with the blank group, the bladder weight of model and electroacupuncture groups were significantly increased (P < 0.05). Compared with the model group, the bladder weight of the electroacupuncture group was decreased (P > 0.05). Compared with the blank group, the urine output of the model group was increased ( P < 0.05). Compared with the blank group, the urine output of the electroacupuncture group was increased ( P > 0.05). Compared with the blank group, the serum BUN of the model group was increased ( P < 0.05). Compared with the blank group, the serum BUN of the electroacupuncture group was increased ( P > 0.05). Compared with the blank group, the urine protein of the model group was increased ( P < 0.05). Compared with the blank group, the urine protein of the electroacupuncture group was increased ( P > 0.05). The expression of NGF, p-TrkA, and p-AKT in the model and electroacupuncture groups was obviously higher than that in the blank group ( P < 0.05). The expression of NGF, p-TrkA, and p-AKT in the electroacupuncture group was higher than that in the model group. The expression of TrkA and AKT were unchanged in blank, model, and electroacupuncture groups ( P > 0.05). After tail vein injection with siNGF lentivirus, the expression of NGF in the model/siNGF group and electroacupuncture/siNGF group was significantly decreased ( P < 0.05). And the protein level of p-AKT and p-TrkA was significantly lower than that of the model and electroacupuncture groups ( P < 0.05). CONCLUSION: Sacral electroacupuncture therapy can improve the expression of both NGF/TrkA signaling and AKT signaling in the local nerve of the damaged spinal cord, inhibit apoptosis of the damaged spinal cord, protect nerve cells, and promote the recovery of the damaged nerve. At the same time, electroacupuncture can promote the coordination of micturition reflex and improve neurogenic bladder function after the spinal cord injury.