RT Journal Article
SR Electronic
T1 Optogenetic silencing of primary afferents reduces evoked and ongoing bladder pain
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 167841
DO 10.1101/167841
A1 Vijay K. Samineni
A1 Aaron D. Mickle
A1 Jangyeol Yoon
A1 Jose G. Grajales-Reyes
A1 Melanie Pullen
A1 Kaitlyn Crawford
A1 Kyung Nim Noh
A1 Graydon B. Gereau
A1 Sherri Vogt
A1 H. Henry Lai
A1 John A. Rogers
A1 Robert W. Gereau IV
YR 2017
UL http://biorxiv.org/content/early/2017/08/02/167841.abstract
AB Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) suffer from chronic pain that severely affects quality of life. Although the underlying pathophysiology is not well understood, inhibition of bladder sensory afferents temporarily relieves pain. Here, we explored the possibility that optogenetic inhibition of bladder sensory afferents could be used to modulate bladder pain. Specifically, we chose to study the role of Nav1.8+ sensory afferents before and after induction of a mouse model of bladder pain. The light-activated inhibitory proton pump Archaerhodopsin (Arch) was expressed under control of the Nav1.8+ promoter to selectively silence these neurons. Optically silencing Nav1.8+ afferents significantly blunted the evoked visceromotor response to bladder distension and led to small but significant changes in bladder function. To study of the role of these fibers in freely behaving mice, we developed a fully implantable, flexible, wirelessly powered optoelectronic system for the long-term manipulation of bladder afferent expressed opsins. We found that optogenetic inhibition of Nav1.8+ fibers reduced both ongoing pain and evoked cutaneous hypersensitivity in the context of cystitis, but had no effect in uninjured, naïve mice. These results suggest that selective optogenetic silencing of bladder afferents may represent a potential future therapeutic strategy for the treatment of bladder pain.