Marc J. Rogers

Somatic modulation of spinal reflex bladder activity mediated by nociceptive bladder afferent nerve fibers in cats

The goal of the present study was to determine if supraspinal pathways are necessary for inhibition of bladder reflex activity induced by activation of somatic afferents in the pudendal or tibial nerve. Cats anesthetized with α-chloralose were studied after acute spinal cord transection at the thoracic T9/T10 level. Dilute (0.25%) acetic acid was used to irritate the bladder, activate nociceptive afferent C-fibers, and trigger spinal reflex bladder contractions (amplitude: 19.3 ± 2.9 cmH2O). Hexamethonium (a ganglionic blocker, intravenously) significantly (P < 0.01) reduced the amplitude of the reflex bladder contractions to 8.5 ± 1.9 cmH2O. Injection of lidocaine (2%, 1-2 ml) into the sacral spinal cord or transection of the sacral spinal roots and spinal cord further reduced the contraction amplitude to 4.2 ± 1.3 cmH2O. Pudendal nerve stimulation (PNS) at frequencies of 0.5-5 Hz and 40 Hz but not at 10-20 Hz inhibited reflex bladder contractions, whereas tibial nerve stimulation (TNS) failed to inhibit bladder contractions at all tested frequencies (0.5-40 Hz). These results indicate that PNS inhibition of nociceptive afferent C-fiber-mediated spinal reflex bladder contractions can occur at the spinal level in the absence of supraspinal pathways, but TNS inhibition requires supraspinal pathways. In addition, this study shows, for the first time, that after acute spinal cord transection reflex bladder contractions can be triggered by activating nociceptive bladder afferent C-fibers using acetic acid irritation. Understanding the sites of action for PNS or TNS inhibition is important for the clinical application of pudendal or tibial neuromodulation to treat bladder dysfunctions.

Propranolol, but not naloxone, enhances spinal reflex bladder activity and reduces pudendal inhibition in cats

This study examined the role of β-adrenergic and opioid receptors in spinal reflex bladder activity and in the inhibition induced by pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS). Spinal reflex bladder contractions were induced by intravesical infusion of 0.25% acetic acid in α-chloralose-anesthetized cats after an acute spinal cord transection (SCT) at the thoracic T9/T10 level. PNS or TNS at 5 Hz was applied to inhibit these spinal reflex contractions at 2 and 4 times the threshold intensity (T) for inducing anal or toe twitch, respectively. During a cystrometrogram (CMG), PNS at 2T and 4T significantly (P < 0.05) increased bladder capacity from 58.0 ± 4.7% to 85.8 ± 10.3% and 96.5 ± 10.7%, respectively, of saline control capacity, while TNS failed to inhibit spinal reflex bladder contractions. After administering propranolol (3 mg/kg iv, a β₁/β₂-adrenergic receptor antagonist), the effects of 2T and 4T PNS on bladder capacity were significantly (P < 0.05) reduced to 64.5 ± 9.5% and 64.7 ± 7.3%, respectively, of the saline control capacity. However, the residual PNS inhibition (about 10% increase in capacity) was still statistically significant (P < 0.05). Propranolol treatment also significantly (P = 0.0019) increased the amplitude of bladder contractions but did not change the control bladder capacity. Naloxone (1 mg/kg iv, an opioid receptor antagonist) had no effect on either spinal reflex bladder contractions or PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly (P < 0.05) reduced the amplitude of the reflex bladder contractions. This study indicates an important role of β₁/β₂-adrenergic receptors in pudendal inhibition and spinal reflex bladder activity.

Role of glycine in nociceptive and non-nociceptive bladder reflexes and pudendal afferent inhibition of these reflexes in cats.

This study examined the role of glycinergic transmission in nociceptive and non‐nociceptive bladder reflexes and in inhibition of these reflexes by pudendal nerve stimulation (PNS).

Role of spinal metabotropic glutamate receptor 5 in pudendal inhibition of the nociceptive bladder reflex in cats

This study examined the role of spinal metabotropic glutamate receptor 5 (mGluR5) in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in the inhibtion of this reflex by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats after spinal cord transection at the T9/T10 level, intravesical infusion of 0.25% acetic acid irritated the bladder, activated nociceptive C-fiber afferents, and induced spinal reflex bladder contractions of low amplitude (<50 cmH2O) and short duration (<20 s) at a smaller bladder capacity ∼80% of saline control capacity. PNS significantly (P < 0.01) increased bladder capacity from 85.5 ± 10.1 to 137.3 ± 14.1 or 148.2 ± 11.2% at 2T or 4T stimulation, respectively, where T is the threshold intensity for PNS to induce anal twitch. MTEP {3-[(2-methyl-4-thiazolyl)ethynyl]pyridine; 3 mg/kg iv, a selective mGluR5 antagonist} completely removed the PNS inhibition and significantly (P < 0.05) increased bladder capacity from 71.8 ± 9.9 to 94.0 ± 13.9% of saline control, but it did not change the bladder contraction amplitude. After propranolol (3 mg/kg iv, a β1/β2-adrenergic receptor antagonist) treatment, PNS inhibition remained but MTEP significantly (P < 0.05) reduced the bladder contraction amplitude from 18.6 ± 2.1 to 6.6 ± 1.2 cmH2O and eliminated PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly (P < 0.05) reduced the bladder contraction amplitude from 20.9 ± 3.2 to 8.1 ± 1.5 cmH2O on average demonstrating that spinal reflexes were responsible for a major component of the contractions. This study shows that spinal mGluR5 plays an important role in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in pudendal inhibition of this spinal reflex.

MP56-20 COMPARISON OF CLINICIAN AND PATIENT MEASUREMENTS USING A MOBILE PHONE APPLICATION TO ASSESS PENILE ANGULATION

METHODS: Penile tissues from 12 Scx-GFP mice with ages 4 week, 5 week, 6 week, and 1.2 years, were dissected and processed following routine histology protocols. 6mm thick sections were stained with H&E, Massons’ trichrome (TRI), Verhoeff’s elastin (ELA), and DAPI. All sections were imaged using bright field or fluorescence microscopy techniques. Cell orientations along collagen fibers with age were analyzed using Image J Fiji. RESULTS: Figure: With age, CCG illustrated well-oriented struts at an angle of 32 to the baculum. Additionally, scleraxis and elastin expressions, and smooth muscle content increased within the struts, specifically in the 6 week-old mice. The expression of scleraxis indicated that the CCG contains mechanoactive collagenous and elastin-ridden struts that support biomechanical function of the baculum. Within the CCG of the mouse, there was more sinusoidal space in the younger age groups (4-6 weeks), and this space decreased with age, and elastin expression increased significantly (see 1 year). Compared to the CCG (A,C,E,G), the CCP (B,D,F,H) illustrated significantly lower expressions of scleraxis, elastin, and smooth muscle. CONCLUSIONS: The collagen-producing fibroblasts within the CCG and CCP express scleraxis, indicative of local mechanoactive areas. Based upon orientation of cells expressing scleraxis, the biomechanical function of the CCP is to push the glans of the penis like a piston, while the CCG stiffens the penis during erection and pulls the glans of the penis back into the prepuce post-erection. The CCG is similar to the HCC with regard to compositional ratio of collagen to muscle, elastin localization, and biomechanical function and as such is a good model to study human penile physiology.

MP51-11 UTILIZATION OF A SURGICAL VIDEO CURRICULUM TO AUGMENT RESIDENT LEARNING

INTRODUCTION AND OBJECTIVES: Iatrogenic urethral catheter related injuries are common and have been shown to correlate with inadequate training among medical professionals. Urethral catheterization (UC) is a common procedure and often one of the first attempted by medical trainees. Simulation training enhances medical procedure teaching by decreasing trainee anxiety, improving patient safety and efficiently tailoring the experience for the learners, thus optimizing education. We sought to create an efficacious simulation model to teach medical students and residents male UC. METHODS: We developed a 50-minute educational curriculum utilizing didactic presentation and a banana with ends removed and longitudinal core created as a simulation model for the male urethra (00Penana00). The presentation focused on UC indications, male urethral anatomy, structure of standard and Coude catheters, and safe technique for UC. Procedural teaching utilized modified Payton technique; 1) Expert demonstration, 2) Explanation of steps, 3) Expert-guided Learner performance, 4) Learner-guided learner performance, 5) Independent Learner performance. Subjects completed pre and post intervention survey assessments to determine efficacy. Surveys measured learner knowledge and self-reported confidence at performing male UC. RESULTS: 126 learners participated in the workshop and (29 MS1, 40 MS2, and 60 PGY1) completed pre and post assessments. Prior to intervention, among medical students 36% and 1% had observed UC and 6% and 0% had performed UC using standard Foley and Coude, respectively. Following intervention, combined knowledge scores increased from 13 16% to 85 20% correct. On a 10 point scale, learners self reported confidence increased from 3.3 2.1 to 8.2 1.5 for male urethral anatomy, 1.7 1.4 to 7.9 1.6 for standard Foley UC, and 1.2 0.6 to 7.8 1.9 for Coude UC. On a 10 point scale with 10 representing very helpful, learners described the Penana model with a mean value of 8.6 1.9. Finally, 78% and 20% were extremely likely and likely, respectively, to recommend the course to a friend. CONCLUSIONS: The Penana is a highly efficacious simulation model for teaching medical students and residents safe UC technique. The low cost and universal availability of the materials makes the model easily accessible for any resource-limited education setting.

MP12-07 THE ROLE OF GLYCINE IN PUDENDAL NERVE STIMULATION AND BLADDER OVERACTIVITY

INTRODUCTION AND OBJECTIVES: Recent fMRI studies revealed supraspinal networks in response to bladder filling involved in perception and processing of bladder distension. However significance of supraspinal network activity and network localizations varied largely due to the different filling protocols. Therefore, our aim was to standardize filling paradigms using a MR-synchronized pump system for accurate timing and filling volume. METHODS: 31 right-handed healthy subjects, 16 women and 15 men, mean age 34 years (range 19e54) with no history of urinary urgency and/or urinary incontinence were included, were prospectively investigated using a 3 Tesla Phillips scanner. After catheterization, bladder was pre-filled until a persistent desire to void was perceived by each subject. The scan paradigm comprised automated, repetitive bladder filling of 100 mL body warm saline over 15sec by using a MRcompatible pump system, i.e. block design study. Neuroimaging data was analyzed with SPM8. Blood-oxygenation-level dependent signal analysis during bladder filling was compared to rest, i.e. pre-filled bladder. Second-level random effects group analysis was corrected for gender, age and total intracranial volume and was performed to account for between-subject variability, i.e. within-group results at P1⁄40.05 familywise error rate (FWE). RESULTS: 3 subjects, 2 women and 1 man, were excluded from further analysis due to excessive head motions. Within-group results from the remaining 28 subjects revealed activation in the following brain regions: bilateral insula, left inferior parietal lobe (BA40) and right frontal inferior operculum (BA44). CONCLUSIONS: Automated, repetitive bladder filling of body warm saline elicited robust brain activity on a high significance level in specific areas known to be involved in supraspinal lower urinary tract control.