Bladder pain and dysfunction are sources of profound debilitation for millions of people in the United States with interstitial cystitis/bladde pain syndrome, overactive bladder, and neurogenic bladder. Current treatments for these disorders are ineffective and do not address the underlying pathology. A substantial barrier to the development of improved therapeutics is an insufficient understanding of mechanisms by which the bladder is controlled. Progress will depend critically on the development of new technologies in neural interfaces. In particular, a combination of optogenetic approaches along with new, wireless optoelectronic systems and electronic hardware for nerve recording and electrical stimulation will provide a unique set of tools for enhanced insights into peripheral organ control. Additionally, the ability to measure, in real-time, neural inflammation and to programmably deliver local anti-inflammatory agents at the neural interface will not only allow robust, high performance chronic integration, but also further the understanding of maintenance at nerve- device interfaces in other applications. In this proposal, we develop a suite of soft, fully-implantable microscale devices with advanced design features specifically configured to minimize and mitigate inflammation for essentially permanent integration with the targeted nerves.
In Aim 1, we propose to integrate optogenetic technologies with fully-implantable wireless systems for inhibition of peripheral neurons innervating the bladder.
In Aim 2, we propose to integrate ultra-thin, flexible electrode technology and novel neuroinflammatory monitors to the wireless control of bladder peripheral nerves.
In Aim 3, we integrate a fully-implantable, wirelessly programmable microfluidic platform for closed-loop maintenance of the chronic nerve interface. Our collaborative team has extensive success merging technologies into unified multi-modal devices and subsequently applying them to the mechanistic study of neuronal subpopulations. The technology produced by these aims will be optimally positioned to study mechanisms of control of end-organ function, and to do so in a way that is minimally invasive.

Public Health Relevance

Bladder pain and dysfunction impacts millions of people in the United States. Current treatments for these disorders are often ineffective and do not address the underlying pathology. This proposal develops new technologies that will allow studies that provide unprecedented understanding of mechanisms by which the bladder is controlled and by which bladder pain arises.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Demonstration--Cooperative Agreements (U18)
Project #
3U18EB021793-02S1
Application #
9534864
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Wolfson, Michael
Project Start
2015-09-30
Project End
2018-07-31
Budget Start
2016-08-01
Budget End
2018-07-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Washington University
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Mickle, Aaron D; Gereau 4th, Robert W (2018) A bright future? Optogenetics in the periphery for pain research and therapy. Pain 159 Suppl 1:S65-S73
Hibberd, Timothy J; Feng, Jing; Luo, Jialie et al. (2018) Optogenetic Induction of Colonic Motility in Mice. Gastroenterology 155:514-528.e6
DeBerry, Jennifer J; Samineni, Vijay K; Copits, Bryan A et al. (2018) Differential Regulation of Bladder Pain and Voiding Function by Sensory Afferent Populations Revealed by Selective Optogenetic Activation. Front Integr Neurosci 12:5
Samineni, Vijay K; Mickle, Aaron D; Yoon, Jangyeol et al. (2017) Optogenetic silencing of nociceptive primary afferents reduces evoked and ongoing bladder pain. Sci Rep 7:15865
Copits, Bryan A; Pullen, Melanie Y; Gereau 4th, Robert W (2016) Spotlight on pain: optogenetic approaches for interrogating somatosensory circuits. Pain 157:2424-2433