Neural Mechanism Of Urinary Bladder Dysfunction Following Chronic Constipation

Background and objectives Chronic constipation(CC) is one of the most common symptoms of the digestive system, and the morbidity increases according to the age. Long-term severe constipation affects not only the function of the digestive system ,but also the function of urinary system, which may result in a urinary bladder dysfun- ction .The pathophysiology of chronic constipation and voiding disfunction is not well clarified due to it's myriad of the etiology ,the pathology and the symptoms as well. The therapeutic outcome of urinary bladder dysfunction affected by chronic constiopation is unsatisfactory using available regimens and the patients suffered too much from this disease. Hard stools, infrequent stools and the need for excessive straining are the main manifestations of chronic constipation.The urinay bladder disfunction symptoms such as frequent micturition , urgency , dysuresia and so on may also induced by a long-term severe constipation. However, with respect to urinary bladder dysfunction after obstipation, little is clarified with serval controversies. Many investigations clarified the voiding dysfunction to the mechanical obstruction at posterior urethra or to the stool withholding , but in some patients, without urethral obstruction after the stool softened, symptoms and abnormal urodynamic findings still exist. Thus, further study on the responsible mechanism.would bu needed.So far, many scholars have found that there are some neural reflexes existing among mutual viscera organs and between viscera organs and some part in the body. A stimulation on a viscera organ or some part of it's body could affect another organs's function related to it. There are reports of these neural reflexes related to the urinary bladder, too. The abnormal bladder function may be the common reason for the voiding dysfunction.Is voiding dysfunction associated with chronic constipatioin caused by a possible neural reflex between the rectum and urinary bladder? To our knowledge, there are few reports on this This study will concentrate on the neural mechanism of abnormal micturition after chronic constipation and suggest a potential neuromodulational therapy for voiding dysfunction of chronic constipation.Methods The neural reflex between the rectum and urinary bladder was studied by physiological, neuroanatomical and functional verified in femal Sprague Dawley rats, to clarify the neural mechanism of the urinary bladder disfunction induced by chronic constipation.1. The rats were intragastric administration with 0.04% loperamide hydrochloride twice a day for five days, and their functional changes of urinary bladder were immediately detected with filling cystometry .The loperimede hydrochloride was replaced by 0.9% saline in control group.2. The bladder myoelectrical activities were isochronously recorded with isochronously rectum electrically stimulation. The role of the brain and spinal cord in the neural reflex and reflex pathway were verified by the lidocaine blocking on the neural conducting in rectum, executing the animals, transecting the cervical cord, disconnecting and resecting the sympathetic nerve stem in lumbar and resecting the parasympathetic nerve in lumbosacral area respectively.3. With the a double-label-fluorescence assay, double labeled dorsal root ganglia(DRG) cells in lumbosacral area and axon reflex was observed underwent the Propidium Iodide(PI) fluorescence injected into the wall of the rectum and the Bisbenzimide(Bb) fluorescence injected into the wall of urinary bladder respectively.Results 1.The rats were successfully constipated with intragastric administration with0.04% loperamide hydrochloride. Five days later , filling cystometry were performed. In comparison with pre-administered, the constipated stimulation to the rectum made basic pressure, pre-micturition pressure and micturition pressure significantly increased (p<0.01), bladder volume and bladder compliance significantly lowered (p<0.01), and unstable bladder occured in 65% rats'urinary baldder. In control group, those urodynamic parameters were not significantly changed(p>0.05). These results may indicated that the constipation might cause the bladder functions changed in rats and provided the functional proofs for the abnormal bladder functions induced by chronic constipation.2. The stable myoelectrical wave could be recorded in the bladder wall when the tunica muscularis recti was stimulated by the electricity in normal rats. The waveform has shapes typical of slow wave, and the latent period and amplilude of wave were 20.23±1.72ms and 2975.82±869. 47uv respectively. This indicated there was a association between rectum and urinary bladder.3. The latent period and amplilude of myoelectrical wave of urinary bladder was gradually extended and reduced respectively at 2min, 5min and 10min after blocking the excitatory conduction of tunica muscularis recti nerve in the wall of the rectum with the lidocaine, which are statistically significant (p<0.01) comparay with those before blocking. The myoelectrical wave of urinary bladder weakened and than almost disappeared after executing the animals by the overdose anesthetic. This indicated that the wave was not the electrical wave diffusion from the rectum, but a neural reflex between the rectum and urinary bladder.4. The latent period and amplilude of myoelectrical wave of urinary bladder were not significantly changed after transecting the cervical cord. They were extended and reduced respectively after destroying the sympathetic nerve stem in homolateral T13～L5, the change was significantly different comparing with pre-destroying(P<0.01). The myoelectrical wave of urinary bladder almost disappeared after resecting the parasympathetic nerves in homolateral L6～S3. These results suggested that the parasympathetic central nervous system(CNS) in lumbosacral area might played a key role in the rectum-urinary bladder neural reflex while the role of the sympathetic CNS in lumbar was minor, and the CNS in brain might seldom influenc the neural reflex.5. Many fluorescent single labeled cells and double labeled cells were found in the L1～L3 and L6～S3 DRG, with a percentage of fluorescent double-labeled cells was 15.2±2.2%. The fluorescent double labeled cells were mainly the small neural cells in the L1～L2 and L6～S3. All these indicated that the DRG cells in lumbosacral area innervated to the rectum and urinary bladder and it could be one of reflex paths between rectum and urinary bladder, which provided the proofs of morphology and neuroanatomy for the neural mechanism of the abnormal bladder functions induced by chronic constipation .Conclusions and prospects 1. This study confirmed that the constipation induced by loperamide hydrochloride could cause the bladder functions changed in rats, and the change may be a kind of reason of voiding dysfunction in clinic with a mechanism of neural reflex between the rectum and urinary bladder. 2. there was a mediation with the neural reflex between the rectum and urinary bladder that the constipated or other nocuous stimulus to the rectum could cause the bladder functions changes in rats, and the main mechanism would be the viscero-viscer reflex of DRG cells in lumbosacral area of spinal cord.3. Bladder functions could be modulated by this reflex when the rectum subjected to constipated or other nocuous stimulus. The hypothesis of the neural reflex path: the excitation be conducted to spinal cord mainly through the parasympathetic nerve afferent fibers after the rectum subjected to nocuous stimulus, and then initly activate the viscero-viscer reflex of DRG cells in lumbosacral area of spinal cord, which may antidromic activation of vesical afferent fibers, finally resulting in bldder functions changed. The findings of this study may suggest a potential neuromodulational therapy for voiding dysfunction of chronic constipation, but further studies on other potential paths and mechanisms of the rectum-urinury bladder reflex woule be performed.