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Translating peripheral bladder afferent mechanosensitivity to neuronal activation within the lumbosacral spinal cord of mice

Date

2019

Authors

Grundy, L.
Harrington, A.M.
Caldwell, A.
Castro, J.
Staikopoulos, V.
Zagorodnyuk, V.P.
Brookes, S.J.H.
Spencer, N.J.
Brierley, S.M.

Editors

Advisors

Journal Title

Journal ISSN

Volume Title

Type:

Journal article

Citation

Pain, 2019; 160(4):793-804

Statement of Responsibility

Luke Grundy, Andrea M. Harrington, Ashlee Caldwell, Joel Castro, Vasiliki Staikopoulos, Vladimir P. Zagorodnyuk, Simon J.H. Brookes, Nick J. Spencer, Stuart M. Brierley

Conference Name

DOI

10.1097/j.pain.0000000000001453

Abstract

Primary afferent neurons transduce distension of the bladder wall into action potentials that are relayed into the spinal cord and brain, where autonomic reflexes necessary for maintaining continence are coordinated with pathways involved in sensation. However, the relationship between spinal circuits involved with physiological and nociceptive signalling from the bladder has only been partially characterised. We used ex vivo bladder afferent recordings to characterise mechanosensitive afferent responses to graded distension (0-60 mm Hg) and retrograde tracing from the bladder wall to identify central axon projections within the dorsal horn of the lumbosacral (LS) spinal cord. Labelling of dorsal horn neurons with phosphorylated-MAP-kinase (pERK), combined with labelling for neurochemical markers (calbindin, calretinin, gamma aminobutyric acid, and parvalbumin) after in vivo bladder distension (20-60 mm Hg), was used to identify spinal cord circuits processing bladder afferent input. Ex vivo bladder distension evoked an increase in primary afferent output, and the recruitment of both low- and high-threshold mechanosensitive afferents. Retrograde tracing revealed bladder afferent projections that localised with pERK-immunoreactive dorsal horn neurons within the superficial laminae (superficial dorsal horn), dorsal gray commissure, and lateral collateral tracts of the LS spinal cord. Populations of pERK-immunoreactive neurons colabelled with calbindin, calretinin, or gamma aminobutyric acid, but not parvalbumin. Noxious bladder distension increased the percentage of pERK-immunoreactive neurons colabelled with calretinin. We identified LS spinal circuits supporting autonomic and nociceptive reflexes responsible for maintaining continence and bladder sensations. Our findings show for the first time that low- and high-threshold bladder afferents relay into similar dorsal horn circuits, with nociceptive signalling recruiting a larger number of neurons.

School/Discipline

Dissertation Note

Provenance

Description

Access Status

Rights

© 2018 International Association for the Study of Pain

License

Grant ID

http://purl.org/au-research/grants/nhmrc/1126378
 http://purl.org/au-research/grants/nhmrc/1083480
 http://purl.org/au-research/grants/nhmrc/1139366
 http://purl.org/au-research/grants/nhmrc/1140297
 http://purl.org/au-research/grants/arc/DE130100223
 http://purl.org/au-research/grants/nhmrc/1105277
 http://purl.org/au-research/grants/nhmrc/1127140

Published Version

https://doi.org/10.1097/j.pain.0000000000001453

Call number

Persistent link to this record

http://hdl.handle.net/2440/121193