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Purpose: Although the co-occurrence of interstitial cystitis (IC) and endometriosis (ENDO) is remarkably high, the exact pathophysiology for this co-occurrence is unknown. The convergence of the inputs from the involved structures to the same neuronal centers may suggest neuronal hyperexcitability as a mechanism for this co-occurrence., Methods: The present study aimed to investigate the association between IC and ENDO, by studying the changes in brainstem responses to cystometry in a rat model of ENDO and cyclophosphamide (CYP)-induced IC using c-fos immunohistochemistry., Results: Following cystometry the brainstem areas that had significant increase in c-fos expression in ENDO alone included: periaqueductal gray (PAG) nuclei, dorsal raphe nucleus, raphe obscurus nucleus, kolliker- Fuse areas, and area postrema. However, the brainstem areas that had increased significantly in the c-fos expression in the ENDO and CYP treated animals included: gigantocellular nucleus, lateral paragigantocellular nucleus, caudoventrolateral nucleus, rostroventrolateral/caudoventrolateral nucleus, lateral reticular nucleus, locus coeruleus, lateral PAG, raphe pallidus nucleus, raphe magnus nucleus, rostroventrolateral nucleus, dorsal motor nucleus of vagus, and solitary tract nucleus. Whereas only lateral parabrachial nucleus showed significant increase in c-fos expression in CYP treated animals alone., Conclusions: The results of the present study demonstrate the overlap of brainstem nuclei that are excited by urinary bladder under ENDO and IC conditions. The pattern of hyperexcitability of the brainstem nuclei may help in understating the pathophysiology of IC and ENDO conditions., (© 2024 Wiley Periodicals LLC.)

Purpose: Although recent literature provides increasing evidence concerning urinary bladder innervation by vagal afferents, the functional aspects and the conditions at which these afferents are recruited are still unclear., Methods: In the present study, the neuronal responses of nodose ganglion following cystometry, under different models of rat's urinary bladder irritation, cyclophosphamide (CYP), cyclophosphamide with cervical vagotomy (Vx), chronic HCl, and acute HCl, were investigated using c-fos immunohistochemistry., Results: The c-fos expression in the nodose ganglion, following cystometry, was increased significantly in the CYP and chronic-HCl groups compared to the intact, Vx, and acute-HCl groups. In addition, the acute-HCl group showed a significant increase compared to intact animals. Following cervical vagotomy, the expression in the Vx group decreased significantly compared to the CYP group, but was significantly higher than that in the intact group., Conclusion: The results of this study demonstrate the innervation of the vagus afferents to the urinary bladder. This innervation is activated under urinary bladder irritation conditions, which may indicate a possible role of the vagus nerve during urinary bladder pathology., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The involvement of the vagus nerve in the supraspinal neural circuits that control the urinary bladder function, especially during pathological conditions, became increasingly evident. However, the role of brainstem areas in these circuits is not studied yet., Methods: In the present study, using c-fos immunohistochemistry, the roles of the vagus nerve to the responses of the reticular formation to cystometry in cyclophosphamide-treated rats were investigated., Results: Cyclophosphamide treatment significantly increased the c-fos expression in the lateral reticular nucleus (LRt), lateral paragigantocellular nucleus (LPGi), caudal part of the ventrolateral reticular nucleus (CVL), and gigantocellular reticular nucleus (Gi) following cystometry. However, cyclophosphamide treatment didn't have significant effect on c-fos expression in ventrolateral reticular nucleus (VL), rostral part of VL (RVL), raphe pallidus nucleus (RPa), and raphe obscurus nucleus (Rob). Vagotomy significantly demolished the effect of cyclophosphamide in the LRt and LPGi areas without having any significant effect on other reticular formation areas. Whereas, in comparison to normal animals, the vagotomised animals didn't show any significant changes in c-fos expression., Conclusion: The results of this study demonstrate the involvement of the reticular formation areas, particularly the ventral part, in processing urinary bladder function under cystitis condition. It also demonstrates the contribution of the vagus nerve in these processes., Competing Interests: None., (AJCEU Copyright © 2023.)

Background: Predicting the behavior of bladder cancer by easy noninvasive methods and with less cost is needed. Fibulin-3 (EFEMP1), a glycoprotein of the extracellular matrix that is encoded by the gene EFEMP1, has been nominated as one of the potential mediators of muscle invasion in bladder cancer., Methods: In this tissue microarray-based immunohistochemical study, fibulin-3 level of expression was evaluated using a semiquantitative scoring system and was correlated with patient's age and sex and tumor grade and stage., Results: A total of 160 urothelial carcinoma cases were analyzed. The age of the patients ranged from 25 to 91 years (mean, 60.15; SD, 11.60). Fibulin-3 was significantly associated with muscle invasion and overall tumor stage (p = 0.033 and 0.02, respectively). Fibulin-3 expression was nonsignificantly associated with tumor grade (p = 0.092) CONCLUSIONS: We found that the expression of fibulin-3 is significantly associated with muscle invasion in urinary bladder urothelial carcinoma. However, the prognostic role of fibulin-3 needs further investigations., (© 2022. The Author(s).)

Objectives: Infertility is one of the major concerns for male patients following spinal cord injury (SCI). Although the severity of the injury has a large impact on extent of infertility, the effect of exact injury extent (with specific affected spinal tracts) on fertility is not studied yet., Materials and Methods: In the present study, sperm parameters, locomotion scores, and hormonal changes were evaluated following dorsal one third SCI (1/3 SCI), dorsal two third SCI (2/3 SCI), and complete spinal cord transection (TX) at T8 spinal level in male rats., Results: Sperm count decreased significantly following 1/3 SCI and Tx compered to normal (control and sham). In addition, sperm count decreased significantly in Tx compared to 1/3 SCI and 2/3 SCI. Concerning sperm motility, although, percentage of motile sperms decreased significantly in Tx group in comparison to all other groups, the percentage of rapid progressive motile sperms (RPM) decreased significantly in all SCI groups compared to normal. Meanwhile, locomotion score (BBB-score) showed a significant progressive decrease following SCI compared to normal or within SCI groups. However, there was no significant changes in the serum hormonal and seminal fructose concentrations following SCI compared to normal., Conclusions: These results show that understanding the extent of SCI, the affected spinal tracts, and the resultant locomotion deficits may help to predict the deficits in sperm parameters and hence fertility potentials.

The cross talk between external genitalia and urinary bladder could be used as part of management to certain pathological conditions affecting urinary bladder. Since urinary bladder function is also affected by pathologies of other organs (e.g., colon and esophagus), the effect of genitalia stimuli on parameters of bladder function in normal or under different pathological conditions needs to be characterized. Cystometry recordings in male rats were used to examine the effect of low-threshold (LT) and high-threshold (HT) stimulation of the scrotum and penis on urinary bladder function. These effects were studied in intact, colon irritation (CI), and esophagus irritation (EI) groups. Although HT penile stimulation had a significant inhibitory effect on micturition reflex in all groups, CI hypersensitized the penile-bladder inhibitory reflex. In addition, LT penile stimulation had a significant inhibitory effect on micturition, which was significant in CI group only. On the other hand, HT penile stimulation in CI group significantly increased the timing parameters of cystometry. Whereas LT and HT penile stimuli in EI group had a significantly increasing effect on all pressure parameters of cystometry. The scrotal stimuli had minimal effect on bladder function in all groups except for HT scrotal stimulation in the CI group, where it had a significant inhibitory effect on micturition reflex and significantly increased the maximum pressure and pressure amplitude of micturition cycles. These results show that CI and EI exacerbate the effects of genitalia stimuli, especially penile stimuli, on urinary bladder function.

Background: Teaching histology as an image-intensive discipline is a major challenge to medical teachers. We compared knowledge retention and student preference after performing comparison-based and traditional methods of teaching practical histology., Methods: We performed a crossover randomized controlled trial. Eighty nine first-year and 37 second-year medical students were randomly assigned to comparison-based or traditional classes in which PowerPoint slides were used. Each teaching approach was then switched to another group for a second tissue set. Quantitative assessment was performed using multiple-choice questions and a questionnaire., Results: The first-year students' overall examination scores were significantly higher in the comparison-based approach compared to the traditional approach for both tissue sets, with a large effect size. Interestingly, even for the second-year students, a significantly higher overall score for one set of tissue samples was observed in the comparison-based approach compared to the traditional approach. The students' responses to all the elements in the questionnaire were significantly in favor of the comparison-based approach., Conclusion: Our findings indicate that the simple implementation of a few histopathology examples can yield a tremendous improvement in first-year medical students' understanding, enjoyment, and engagement in practical histology classes., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Sexual dysfunction, following spinal cord injury (SCI), is highly dependent on the extent of injury. SCI disrupts the supraspinal innervation of the reproductive organs; resulting in structural and functional deficits. Relating the extent of SCI to these changes could eventually improve diagnoses and treatment planning of sexual dysfunction following SCI. In the present study, following chronic SCI of different severities (1/3 dorsal SCI (1/3 SCI), 2/3 dorsal SCI (2/3 SCI), and complete transection (Tx)) at T8 spinal level, histological changes of seminiferous tubules parameters in testis were examined. The diameter of seminiferous tubules (DST) and epithelial height of seminiferous tubules (HST) were significantly decreased in all SCI groups compared to control and sham. In addition, DST in 2/3 SCI and Tx groups and HST in Tx group were significantly decreased in comparison with 1/3 SCI animals. Nonetheless, the diameter of seminiferous tubules' lumen decreased significantly in 2/3 SCI and Tx compared to control, sham, and 1/3 SCI groups. Concerning cellular component, the number of spermatocytes and spermatids layers significantly decreased in both 1/3 and 2/3 SCI in comparison to normal. However, Tx had the most prominent deteriorating effect on these layers; indicating impairment in the process of spermatogenesis. These results show that the spinal tracts are part of the neural circuitries innervating the testis and responsible for their structural support. These tracts are mainly distributed between the lateral and ventral funiculi at T8 spinal level. Consequently, sparing ventral funiculi in the SCI prevents the severe decline in spermatogenesis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The coexistence of different visceral pathologies in patients suffering from irritable bowel syndrome, interstitial cystitis, and other pathologies, necessitates the study of these pathologies under complicated conditions. In the present study, cystometry recordings were used to investigate the effect of distal esophageal chemical irritation on the urinary bladder interaction with distal colon distention, distal esophageal distention, and electrical stimulation of abdominal branches of vagus nerve. Distal esophageal chemical irritation significantly decreased the intercontraction time via decreasing the voiding time. Also, distal esophageal chemical irritation significantly decreased the pressure amplitude by decreasing the maximum pressure. Following distal esophageal chemical irritation, distal esophageal distention was able to significantly decrease the intercontraction time by decreasing the storage time. However, 3 mL distal colon distention significantly increased the intercontraction time by increasing the storage time. On the other hand, following distal esophageal chemical irritation, electrical stimulation of abdominal branches of vagus nerve did not have any significant effect on intercontraction time. However, electrical stimulation of abdominal branches of vagus nerve significantly increased the pressure amplitude by increasing the maximum pressure. The results of this study demonstrate that urinary bladder function and interaction of bladder with other viscera can be affected by chemical irritation of distal esophagus.

The co-occurrence of multiple pathologies in the pelvic viscera in the same patient, such as, irritable bowel syndrome and interstitial cystitis, indicates the complexity of viscero-visceral interactions and the necessity to study these interactions under multiple pathological conditions. In the present study, the effect of distal colon irritation (DCI) on the urinary bladder interaction with distal esophagus distention (DED), distal colon distention (DCD), and electrical stimulation of the abdominal branches of vagus nerve (abd-vagus) were investigated using cystometry parameters. The DCI significantly decreased the intercontraction time (ICT) by decreasing the storage time (ST); nonetheless, DED and Abd-vagus were still able to significantly decrease the ICT and ST following DCI. However, DCD had no effect on ICT following the DCI. The DCI, also, significantly decreased the Intravesical pressure amplitude (P-amplitude) by increasing the resting pressure (RP). Although DED has no effect on the P-amplitude, both in the intact and the irritated animals, the abd-vagus significantly increased the P-amplitude following DCI by increasing the maximum pressure (MP). In the contrary, 3mL DCD significantly increased the P-amplitude by increasing the MP and lost that effect following the DCI. Concerning the pressure threshold (PT), none of the stimuli had any significant changes in the intact animals. However, DCI significantly decreased the PT, also, the abd-vagus and 3mL DCD significantly decreased the PT. The results of this study indicate that chemical irritation of colon complicates the effects of mechanical irritation of esophagus and colon on urinary bladder function.

Purpose: Many studies have demonstrated the convergence of vagal inputs into brainstem centers with inputs from the urinary bladder and colon, as well as the convergence of vagal inputs into other centers controlling the urinary bladder and colon reflexes. However, the effect of the vagal inputs on the interaction between the urinary bladder and other pelvic organs has not been studied. In this study, the effect of bilateral cervical vagotomy on the distal colon to urinary bladder reflex was examined., Methods: Changes to cystometry parameters in response to increased distal colon distensions (1, 2, and 3 ml) were tested in urethane-anesthetized male rats with or without bilateral cervical vagotomy., Results: In animals with intact vagus nerves, 1 and 2 ml distal colon distentions had no significant effects on micturition frequency; however, 3 ml distal colon distention significantly decreased the frequency of micturition cycles. Also, 3 ml distal colon distention inhibited micturition cycles in 37.5 % of these animals. On the other hand, following cervical vagotomy, 1 ml distal colon distention was enough to significantly decrease the frequency of micturition cycles and to inhibit the cycles in 75 % of the animals., Conclusion: These results demonstrate the presence of supraspinal inhibitory regulation, via the vagus nerve, over the distal colon to urinary bladder inhibitory reflex.

In Jordan, the leaves of Laurus nobilis (Family Lauraceae) have been used in folk medicine for the treatment of diarrhea, among other ailments. However, the ethnopharmacology of this plant needs to be scientifically validated. The present work was carried out to evaluate the scientific basis of the antidiarrheal effect of the aqueous extract of L. nobilis leaf. L. nobilis leaf extract significantly inhibited castor oil-induced diarrhea (effective concentration producing 50% of the maximum response [EC(50)]=150±6.4 mg/kg) and reduced castor oil-induced enteropooling in rats (EC(50)=162±5.9 mg/kg). The extract also significantly inhibited intestinal transit of a charcoal meal and exerted a significant dose-dependent relaxation (EC(50)=71±5.3 mg/mL) on rat ileal smooth muscle. The aqueous extract tested positive for flavonoids, alkaloids, and tannins. These results established the efficacy of L. nobilis leaf aqueous extract as an antidiarrheal agent and are consistent with the popular use of the plant in the treatment of gastrointestinal disorders, particularly diarrhea.

Aims: Micturition process is a spinobulbospinal reflex that is affected by the viscero-visceral interactions due to convergent inputs into spinal and/or supraspinal centers controlling that reflex. Although interaction between bladder and other pelvic organs, such as colon, are well studied, the viscero-visceral interaction between urinary bladder and internal organs in other regions are rarely studied., Methods: In the present study, continuous filling cystometry recordings, in male rats, were used to investigate the effects of mechanical stimulation of distal-esophagus (distention), as well as, electrical stimulation of abdominal branches of the vagus nerve on urinary bladder micturition cycles., Results: Distal esophagus distention and electrical stimulation of the vagus nerve significantly increased the micturition frequency through decreasing the time of the storage phase of the micturition cycle. However, bilateral cervical vagotomy eliminated the effects of distal esophagus distention and electrical stimulation of vagus nerve on micturition cycles., Conclusions: The results of this study indicate that there is a viscero-visceral interaction between esophagus and urinary bladder, which is mediated through vagal afferents. Understanding the properties of the viscero-visceral interactions affecting the urinary bladder will help in the diagnosis and management of micturition problems., (Copyright © 2011 Wiley Periodicals, Inc.)

The specific white matter location of all the spinal pathways conveying penile input to the rostral medulla is not known. Our previous studies using rats demonstrated the loss of low but not high threshold penile inputs to medullary reticular formation (MRF) neurons after acute and chronic dorsal column (DC) lesions of the T8 spinal cord and loss of all penile inputs after lesioning the dorsal three-fifths of the cord. In the present study, select T8 lesions were made and terminal electrophysiological recordings were performed 45-60 days later in a limited portion of the nucleus reticularis gigantocellularis (Gi) and Gi pars alpha. Lesions included subtotal dorsal hemisections that spared only the lateral half of the dorsal portion of the lateral funiculus on one side, dorsal and over-dorsal hemisections, and subtotal transections that spared predominantly just the ventromedial white matter. Electrophysiological data for 448 single unit recordings obtained from 32 urethane-anaesthetized rats, when analysed in groups based upon histological lesion reconstructions, revealed (1) ascending bilateral projections in the dorsal, dorsolateral and ventrolateral white matter of the spinal cord conveying information from the male external genitalia to MRF, and (2) ascending bilateral projections in the ventrolateral white matter conveying information from the pelvic visceral organs (bladder, descending colon, urethra) to MRF. Multiple spinal pathways from the penis to the MRF may correspond to different functions, including those processing affective/pleasure/motivational, nociception, and mating-specific (such as for erection and ejaculation) inputs.

In a previous study using male rats, a correlation was found between the development of "at-level" allodynia in T6-7 dermatomes following severe T8 spinal contusion injury and the sparing of some myelinated axons within the core of the lesion epicenter. To further test our hypothesis that this sparing is important for the expression of allodynia and the supraspinal plasticity that ensues, an injury that severs all axons (i.e., a complete spinal cord transection) was made in 15 male rats. Behavioral assessments were done at level throughout the 30-day recovery period followed by terminal electrophysiological recordings (urethane anesthesia) from single medullary reticular formation (MRF) neurons receiving convergent nociceptive inputs from receptive fields above, at, and below the lesion level. None of the rats developed signs of at-level allodynia (versus 18 of 26 male rats following severe contusion). However, the terminal recording (206 MRF neurons) data resembled those obtained previously post-contusion. That is, there was evidence of neuronal hyper-excitability (relative to previous data from intact controls) to high- and low-threshold mechanical stimulation for "at-level" (dorsal trunk) and "above-level" (eyelids and face) cutaneous territories. These results, when combined with prior data on intact controls and severe/moderate contusions, indicate that (1) an anatomically incomplete injury (some lesion epicenter axonal sparing) following severe contusion is likely important for the development of allodynia and (2) the neuronal hyper-excitability at the level of the medulla is likely involved in nociceptive processes that are not directly related to the conscious expression of pain-like avoidance behaviors that are being used as evidence of allodynia.

Varying degrees of neurologic function spontaneously recovers in humans and animals during the days and months after spinal cord injury (SCI). For example, abolished upper limb somatosensory potentials (SSEPs) and cutaneous sensations can recover in persons post-contusive cervical SCI. To maximize recovery and the development/evaluation of repair strategies, a better understanding of the anatomical locations and physiological processes underlying spontaneous recovery after SCI is needed. As an initial step, the present study examined whether recovery of upper limb SSEPs after contusive cervical SCI was due to the integrity of some spared dorsal column primary afferents that terminate within the cuneate nucleus and not one of several alternate routes. C5-6 contusions were performed on male adult rats. Electrophysiological techniques were used in the same rat to determine forelimb evoked neuronal responses in both cortex (SSEPs) and the cuneate nucleus (terminal extracellular recordings). SSEPs were not evoked 2 days post-SCI but were found at 7 days and beyond, with an observed change in latencies between 7 and 14 days (suggestive of spared axon remyelination). Forelimb evoked activity in the cuneate nucleus at 15 but not 3 days post-injury occurred despite dorsal column damage throughout the cervical injury (as seen histologically). Neuroanatomical tracing (using 1% unconjugated cholera toxin B subunit) confirmed that upper limb primary afferent terminals remained within the cuneate nuclei. Taken together, these results indicate that neural transmission between dorsal column primary afferents and cuneate nuclei neurons is likely involved in the recovery of upper limb SSEPs after contusive cervical SCI.

The presence of pelvic visceral inputs to neurons in the rostral medulla that are responsive to electrical stimulation of the abdominal branches of the vagus nerve (VAG-abd) was investigated in a complete chronic T8 spinal transection rat model. Using extracellular electrophysiological recordings from single medullary reticular formation (MRF) neurons, 371 neurons in 15 rats responsive to pinching the ear (search stimulus) were tested for somato-visceral and viscero-visceral convergent responses to stimulation of the following nerves/territories: VAG-abd, dorsal nerve of the penis, pelvic nerve, distention of urinary bladder and colon, penile stimulation, urethral infusion, and touch/pinch of the entire body surface. In addition to these mechanical and electrical stimuli, a chemical stimulus applied to the bladder was assessed as well. Of the total neurons examined, 205 were tested before and 166 tested beginning 20 min after application of a chemical irritant (2% acetic acid) to the urinary bladder (same rats used pre/post irritation). As with intact controls, many ear-responsive MRF neurons responded to the electrical stimulation of VAG-abd. Although MRF neuron responses failed to be evoked with direct (mechanical and electrical nerve) pelvic visceral stimuli, acute chemical irritation of the urinary bladder produced a significant increase in the number of MRF neurons responsive to stimulation of VAG-abd. The results of this study indicate a central effect that potentially relates to some of the generalized below level pelvic visceral sensations that have been documented in patients with complete spinal cord injury.

A number of clinical studies indicate the coexistence of multiple chronic pelvic diseases and pain syndromes. An association between various conditions related to the pelvic viscera may relate to a high degree of central visceral convergence, which is a requisite for the cross-organ coordination that is necessary for their normal functions. In the present study, a population of neurons receiving a high degree of somatovisceral convergence (those in the medullary reticular formation--MRF) was targeted in order to examine the effect of infusing a chemical irritant into one organ on the responsiveness of convergent inputs from various visceral and somatic regions of the body, using electrophysiological techniques. Acute irritation of the urinary bladder (UB) with 2% acetic acid significantly decreased the percentage of convergent MRF neuronal responses to UB distention and urethral infusion and significantly increased the percentage responding to whole body, mainly due to stimulation of the face. Irritation also produced a significant increase in the response duration of MRF neurons to distention of colon as well as the bladder (for those few UB responses that still remained). These results indicate that a pelvic/visceral pathology confined to one organ can affect at least some of the convergent responses from other regions of the body. The findings suggest that MRF neurons contribute to the cross-talk between different regions of the body under both normal and pathological conditions.

Electrophysiological recordings were used to investigate the degree of pelvic/visceral convergent inputs onto single medullary reticular formation (MRF) neurons. A total of 94 MRF neurons responsive to bilateral electrical stimulation of the pelvic nerve (PN) in 12 urethane-anaesthetized male rats were tested for responses to mechanical stimulation of the urinary bladder, urethra, colon and penis, and electrical stimulation of the dorsal nerve of the penis (DNP) and abdominal branches of the vagus. Responses to distension of the bladder were found for 51% (n = 48) of the MRF neurons tested. Of these 48, 71% responded to urethral infusion, 81% responded to colon distension, 100% responded to penile stimulation (and DNP), and 85% responded to vagal stimulation, with 62% responding to stimulation of all four of these territories. This high degree of visceral convergence (i.e. 62%) in a subset of PN-responsive MRF neurons is significantly greater than for the subset of PN-responsive MRF neurons that did not respond to urinary bladder distension (i.e. out of the 46 remaining neurons, none responded to all four of the other pelvic/visceral stimuli combined). These results suggest that the neurons processing information from the urinary bladder at this level of the neural axis are likely to be important for mediating interactions between different visceral organs for the coordination of multiple pelvic/visceral functions.

Single medullary reticular formation (MRF) neurons receive ascending spinal inputs from multiple somatic and pelvic visceral territories. MRF neurons were examined for responses to both pelvic (PN) and vagus (abdominal branches: VAG-abd) nerve stimulation, which dually innervate certain pelvic viscera. Recordings in 12 urethane-anesthetized male rats were performed. Of 121 PN-responsive MRF neurons, 50% responded to VAG-abd. Twenty-seven (22%) responded to colonic distention. All 121 neurons responded to noxious stimulation of somatic territories, including many areas outside the perigenital region (including the hindpaws, ears, face). These data demonstrate input originating from different spinal and cranial nerves. The functional significance of this viscerosomatic convergence to MRF is unknown, but could relate to sensory/autonomic integration for coordinating multiple bodily functions, including reproductive and eliminative events., (Copyright 2004 Lippincott Williams and Wilkins)