The Specific Effect And Afferent Mechanism Of Electroacupuncture At BL32for Overactive Bladder

BackgroundFunction of the bladder is controlled by perch center (located in brain stem and cerebral cortex), sacral spinal cord and peripheral nerve. There are mainly three nerves controlling the bladder—the hypogastric nerve, the pudendal nerve and the pelvic nerve. The hypogastric nerve is the sympathetic nerve. Hypogastric nerve activation in the thoracic10-lumbar2(T10-L2) spinal cord level and could contract the internal smooth muscle sphincter and relax the bladder. The somatic pudendal nerve arises from the nucleus in S2-S4level and controls the rhabdosphincter. The pelvic nerve is parasympathetic nerve. It is the most important nerve sending impulses and regulating emptying of the bladder. The impulses travel in the pelvic nerve and goes into the sacral spinal cord.The bladder afferent pathways are composed of two types of axons:myelinated A8fibers and unmyelinated C fibers. Located in detrusor and urethral smooth muscle, A8fibers transmit signal mainly from mechanoreceptors that detect bladder fullness or wall tension. C fibers could be found in mucosa and submucosal areas and transmit noxious signals and initiate painful sensations. They account for60%～70%in all afferent fibers and are insensitive to mechanical stimulation. Under normal conditions, A8fibers transmit signal from the bladder to the pontine micturition center. The bladder C-fiber nociceptors perform a similar function and signal the central nervous system when people have spinal cord injury or irritative condition in the bladder, which could be viewed as a defense mechanism to eliminate irritants of bacteria. At the same time, patients will have lower urinary tract symptoms like micturition and urgency. Now it is considered that the neuropathological mechanism of OAB is hyperactivity of C fibers. This could be confirmed by capsaicin. Capsaicin could suppress bladder contraction by depleting SP. Research found that capsaicin could be used for bladder hyperactivity.Overactive bladder (OAB) is a storage dysfunction with no obvious reasons, and it is defined by set of symptoms:urgency, with of without urge incontinence, usually with frequency and nocturia. To date, there are no satisfactory therapies for OAB patients, especially for refractory OAB patients. Acupuncture could manage this disease well. Though there is not systematic review about acupuncture for OAB, available medical evidence shows that acupuncture is easy to operate, safe and effective. BL32is an acupoint used often in treatment. Though the effectiveness, how acupuncture can treat the disease is still not known. Some scholars try to explain the mechanism with neurotransmitters. They found that acupuncture could reduce substance P (SP) in the afferent fibers, and they speculated that acupuncture could suppress the hyperactivity of afferent fibers and suppress the bladder activity correspondingly. Some studies try to explain the mechanism from the viewpoint of central nervous system (CNS) and evaluate the effect of acupuncture according to neuron activities of various areas in CNS. Adoption of single indicator in those studies could only make sure that neurotransmitter or neuron activity is a point in the mechanism link, and the whole mechanism is still not clear. In recent years, studies focusing on peripheral nerve concluded that acupuncture suppress bladder hyperactivity through C fibers. But how it works through C fibers and the systematic change of bladder function, neurotransmitter and nerve activity are still not clear.Objective1. To detect whether deep needling at BL32is effective for OAB;2. Set shallow needling group and non point needling group (pointbesides BL32) as controls to detect whether the effect of electroacupuncture at BL32is specific and the key influence factors;3. Try to discuss the relation between acupuncture’s effect and afferent pathway and elucidate the possible mechanism.Methods1. To detect acupuncture’s effect on bladder hyperactivity using cystometry in anesthetized rats. With shallow needling group and non point needling group as controls, to study whether the effect is specific;2. Make principle of deep needling at B132on rat and measure the needling depth to examine the key influence factor;3. Block the C-fiber activity by capsaicin injection to examine the pathways that acupuncture works through;4. Observe the pelvic nerve activity using technique of neurological electrophysiology and analyze the change of nerve activity corresponding to the change of bladder pressure;5. To measure the mRNA expression level of SP and neruokinin B by RT-PCR. Results1. For deep needling at BL32, the needle should get near to or touch the anterior branch of the sacral nerve.The mean depth of deep needling is16.33mm and that of the shallow needle group is6.58mm. Push the needle back to the sacrum with a cotton swab to ensure the tip of the needle is near to or touch the sacral nerve. For shallow needling, stop puncture when the tip of the needle touch the sacrum.2. Eletroacupuncture at BL32could suppress bladder hyperactivity.Deep needling at BL32must be get near to or touch the anterior branch of the sacral nerve.0.25%acetic acid was infused to the rat’s bladder to cause irritation and after that electroacupuncture was given. Using cystometry, we found that electroacupuncture could increase the ICI, decrease the micturition time and the incidence of detrusor instability.3. The effect of electroacupuncture for OAB is specific.Setting shallow needling group and non point needling group (point besides BL32) as controls, we found that both the control groups were not effective for suppressing bladder hyperactivity. Data suggested that the effect of electroacupuncture at BL32was specific and needling at other points in the same nerve innervated area didn’t have the same effect. The key influence factor is needling depth. Only deep needling at B132to stimulate the sacral nerve the bladder hyperactivity could be suppressed.4. Eletroacupuncture works by suppressing C fibers.Capsaicin pretreated rats didn’t show any change in ICI, bladder pressure and micturition time after acetic acid infusion, which meant the bladder of the rat would not be irritated after C fibers were blocked. The indicators above still didn’t change after electroacupuncture suggested that needling didn’t have influence on C-fiber blocked rats. Those results suggested that bladder hyperactivity was caused and suppressed both through C fibers.5. Eletroacupuncture decreased afferent nerve activity and expression of neurotransmitters.Activity of the pelvic nerve before and during each micturition increased after acetic acid infusion, and so was the expression of SP and neruokinin B. After eletroacupuncture at BL32, both nerve activity and expression of neurotransmitters decreased, much lower than those of the model group.ConclusionThe study detected the specific effect of eletroacupuncture and deep needling at BL32for suppressing bladder hyperactivity and the possible mechanism. The results suggested that eletroacupuncture and deep needling at BL32had specific effect for suppressing bladder hyperactivity. The possible mechanism was suppression of neurotransmitters—suppression of C-fiber activity—suppression of bladder contraction.