Open source timed pressure control hardware and software for delivery of air mediated distensions in animal models

Studying the visceral sensory component of peripheral nervous systems can be challenging due to limited options for consistent and controlled stimulation. One method for mechanical stimulation of hollow organs, including colon and bladder, are controlled distensions mediated by compressed air. For example, distension of the bladder can be used as an assay for bladder nociception. Bladder distension causes a corresponding increase in abdominal electromyography, which increases with distension pressure and is attenuated with analgesics. However, the hardware used to control these distensions are primarily all one-off custom builds, without clear directions how to build your own. This has made it difficult for these methods to be fully utilized and replicated as not everyone has access, knowledge and resources required to build this controller. Here we show an open-source Arduino based system for controlling a solenoid valve to deliver timed pressure distensions in the experimental model. This device can be controlled by one of two methods through direct TTL pulses from the experimenters data acquisition software (ex. CED Spike2) or by a graphical user interface, where the user can set the time before, during, and after distension as well as the number of cycles. This systems low cost and relative ease to build will allow more groups to utilize timed pressure distensions in their experiments.Specifications table

Impact of CT-based planning and bladder volume changes on the dosimetry of vaginal vault brachytherapy

Aim: To compare dose to target and organs at risk (OARs) in conventional plan (2D) versus computed tomography (CT)-based three-dimensional (3D) plan in vaginal cuff brachytherapy (VBT) and to compare the effect of bladder distension on target and OARs dosimetry. Materials and methods: Post-hysterectomy patients with an indication for VBT were included in the study. All patients underwent planning CT scans with a full bladder and an empty bladder protocol. For each CT, two plans were generated—one library-based 2D plan and another CT-based 3D plan. Dosimetric parameters were recorded for clinical target volume (CTV) and OARs. Results: A total of 92 observations were made from data collected from 46 patients. Difference between CTV dose in terms of 2D and 3D plans were not statistically significant for CTV (p = 0·11). Significant reduction in D0·1cc, D1cc and D2cc dose parameters were observed in bladder, rectum, sigmoid and bowel doses with the 3D plan (p < 0·001). Bladder distension showed a 20% reduction in dose for bowel (p < 0·001). Bladder distension also showed a 6·12% (p = 0·047) increase in D2cc, but there was a significant reduction in the mean dose to the bladder. Conclusion: Our study demonstrates the dosimetric benefits with 3D CT-based planning for VBT over 2D-based conventional planning and benefit of bladder distension in the reduction of bowel dose without compromising dose to the target volume.

Histamine induces peripheral and central hypersensitivity to bladder distension via the histamine H1 receptor and TRPV1

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common chronic pelvic disorder with sensory symptoms of urinary urgency, frequency, and pain, indicating a key role for hypersensitivity of bladder-innervating sensory neurons. The inflammatory mast cell mediator histamine has long been implicated in IC/BPS, yet the direct interactions between histamine and bladder afferents remain unclear. In the present study, we show, using a mouse ex vivo bladder afferent preparation, that intravesical histamine enhanced the mechanosensitivity of subpopulations of afferents to bladder distension. Histamine also recruited “silent afferents” that were previously unresponsive to bladder distension. Furthermore, in vivo intravesical histamine enhanced activation of dorsal horn neurons within the lumbosacral spinal cord, indicating increased afferent signaling in the central nervous system. Quantitative RT-PCR revealed significant expression of histamine receptor subtypes ( Hrh1– Hrh3) in mouse lumbosacral dorsal root ganglia (DRG), bladder detrusor smooth muscle, mucosa, and isolated urothelial cells. In DRG, Hrh1 was the most abundantly expressed. Acute histamine exposure evoked Ca2+ influx in select populations of DRG neurons but did not elicit calcium transients in isolated primary urothelial cells. Histamine-induced mechanical hypersensitivity ex vivo was abolished in the presence of the histamine H1 receptor antagonist pyrilamine and was not present in preparations from mice lacking transient receptor potential vanilloid 1 (TRPV1). Together, these results indicate that histamine enhances the sensitivity of bladder afferents to distension via interactions with histamine H1 receptor and TRPV1. This hypersensitivity translates to increased sensory input and activation in the spinal cord, which may underlie the symptoms of bladder hypersensitivity and pain experienced in IC/BPS.