Published-IP

This disclosure is directed at techniques and/or systems for identifying and/or treating bladder dysfunction such as urgency, frequency, pelvic pain, [i]et al[/i].  For example, bladder overactivity/pain is caused by hyper excitability within bladder AFFERENT fibers (e.g. C-fibers) and cholinergic EFFERENT nerve fibers. Both afferent and efferent nerves travel through the pelvic nerve into the bladder wall and are normally activated to cause enhanced sensation and detrusor activity. Hyperexcitability of these fibers may underly overactive bladder vis a vis hypersensitivity and detrusor hyperactivity. This invention is to partially cut/ablate the hypersensitive nerve branches to reduce bladder sensation and detrusor contraction.  Depending on the patient’s condition, controlled methods are used to quantitate the amount of partial nerve cut, either unilateral or bilateral transection of one or more branches of the pelvic nerve near detrusor innervation.  A threshold of nerve damage resulting in clinical benefit will be evaluated for efficacy in the treatment of patients with detrusor overactivity, overactive bladder syndromes, pelvic pain, and other pelvic floor pathologies (IBS, bowl urgency, sexual dysfunction, [i]et al[/i]).Quantification of nerve transection will be accomplished with the following procedures:1. A clinician may identify one or more endpoints for measuring visceral sensation. For example, urgency sensation to different volumes of bladder filling is reported with a stimulus-response function.  Bladder capacity is measured and urodynamic function (cystometry) is performed, NIM-like method (nerve stimulation triggered action potentials) is guided during the nerve transection.  Various imaging techniques are used to visualize the hypersensitive fibers innervating target organs (bladder, colon, [i]et al[/i]).  A clinician may identify locations of these identified fibers and select the amount of nerve for transection therapy, and the clinician may then transect the nerves corresponding to the locations and functional response (sensation, cystometry, nerve firing) to reduce the enhanced sensation and overactivity of the detrusor muscle.  Such nerve transection may thus alleviate symptoms related to overactive bladder or other disorders related to pelvic nerve hypersensitivity.  2. Regarding the procedure, this disclosure is directed to C-fiber selective treatment modalities for treating bladder dysfunction in a patient, including methodology for identifying and transecting fibers, especially C-fibers, at respective locations of a detrusor muscle in the bladder of a patient: main pelvic entrance bilaterally close to ureters (Figure 1, Method 1), or outside the bladder through laparoscopic method (Figure 1, Method 2).  Optical and dying technique may be used to aid in the identification of the organ specific fibers (Figure 1, Method 3).  With chronic pain being a potential side effect of partial nerve ablation, then perhaps some perioperative or temporary postoperative (removable temporary PNE-like non tined lead) may prevent pain development. The C fibers may respond to low volume of bladder distention and should be ablated.  A fibers fire during voiding and should be retained.   C-fibers are more sensitive to mechanical stretch, thermal (heat) stimulation, ultrasound, and chemicals like capsaicin (or resiniferatoxin, RTX), botulinum toxin to target C-fibers, [i]et al[/i].   Another way to selectively block unwanted nerve activity is to trigger with a low-volume bladder distension.  The firing nerves are “used” when the bladder is “empty” or “partially” filled.  The method is to target the active fibers and produce a “use-dependent” transection or block.  For example, nerve activity may be sensitive to mechanical (bladder filling), electrical (stimulation-NIM), chemical (pH, heat, [i]et al[/i]) stimulation.  Those stimuli can be used to identify the active fibers.  The active fibers are also sensitive to “damage” with modalities mentioned above.  For example, a “damage” modality is set at a “subthreshold” level, such that only the active nerve is “damaged”.   For another example, like a “micro” closed-loop concept, firing is detected and identified.  They are then selectively damaged.     3. In another aspect, this disclosure is directed to a method for treating bladder dysfunction in a patient, the method includes targeting a first portion of nerve transection in a bladder of the patient (phase 1), wherein the first portion corresponds to a first point of nerve firing, each focal point of the plurality of focal points being identified as functional measurement.  After transecting the first portion of the pelvic nerve a second portion of the nerve firing of the plurality of focal points is identified and transected. The method is an acute procedure and may be repeated after a couple of weeks to years depending on the patients’ response and functional measurements.  4. Nerve regrowth could happyn after acute transection.  In addition to repeat treatments, an ablation maintenance technique such as hyperextend the bladder with a temporary large volume fill may be used to knock out early C-fiber regrowth. 5.  Feasibility study in anesthetized rats is currently being performed at PRL.  In this study, rat bladders are infused with 0.3% acetic acid to create an irritation-based model of “OAB”. Mechanically isolating nerve (bilateral partial nerve damage) increases bladder capacity (ICI: intercontraction interval) and voiding volume (VV) in comparison to naïve rats.  Whole nerve transection further increased bladder capacity.  Bilateral nerve transection made the rat incontinent (no voiding reflex).  The details of results are shown below (Figures 2 and 3).  Pelvic nerve dissection is shown in Figure 4.