Format

Send to

Choose Destination
Cell Rep. 2016 Dec 13;17(11):2901-2912. doi: 10.1016/j.celrep.2016.11.047.

TRPV1 Nociceptor Activity Initiates USP5/T-type Channel-Mediated Plasticity.

Author information

1
Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
2
Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada. Electronic address: zamponi@ucalgary.ca.

Abstract

Peripheral nerve injury and tissue inflammation result in upregulation of the deubiquitinase USP5, thus causing a dysregulation of T-type calcium channel activity and increased pain sensitivity. Here, we have explored the role of afferent fiber activity in this process. Conditioning stimulation of optogenetically targeted cutaneous TRPV1 expressing nociceptors, but not that of non-nociceptive fibers, resulted in enhanced expression of USP5 in mouse dorsal root ganglia and spinal dorsal horn, along with decreased withdrawal thresholds for thermal and mechanical stimuli that abated after 24 hr. This sensitization was drastically reduced by an interfering peptide that prevented USP5-Cav3.2 association. Sensitization was relieved by pharmacological block of TRPV1 afferents, but not of myelinated neurons. In spinal cord slice recordings, we could optogenetically trigger an activity-dependent potentiation of presynaptic neurotransmission in the spinal dorsal horn that relied on Cav3.2 channel activity. This neuronal-activity-induced USP5 upregulation may underlie a protective, transient sensitization of the pain pathway.

KEYWORDS:

Cav3.2; DRG; T-type; TRPV1; USP5; optogenetics; pain; spinal cord

PMID:
27974205
DOI:
10.1016/j.celrep.2016.11.047
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center