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Transcriptionally Defined Subpopulations of Cutaneous Neurons: Effects of Nerve Injury and Regeneration

Adelman, Peter (2016) Transcriptionally Defined Subpopulations of Cutaneous Neurons: Effects of Nerve Injury and Regeneration. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Primary sensory neurons are responsible for cutaneous somatosensory transduction. These neurons can transduce mechanical force, temperature, and chemical sensitivity, which we perceive as pressure, position, heat, cold, itch, and pain. It has long been recognized that different afferents are specific for distinct modalities, but it has not been clear if afferent sensitivities represent a continuum or unique populations of afferents with common properties. I found that mouse dorsal root ganglion afferents can be clearly divided into groups by their
transcriptional expression and that these groups share common modality sensitivities and functional properties. Further investigation revealed that the levels of some individual transduction channels may be an even more accurate way to track modality sensitivity, giving a
potential molecular signature for function in murine afferents. These findings imply that recognized histological projection bands in the spinal cord (Substance P, CGRP, IB4, etc.) reflect subpopulations of afferents with unique properties that are projecting to unique areas of the spinal cord. This is relevant to sensory coding models, but may also be very important for the development of neuropathic pain after nerve injury. Nerve injury and regeneration alters mRNA and protein expression, and causes parallel changes in afferent properties. These functional
changes in afferents could cause unusual activity in corresponding spinal cord circuits (e.g. a spinal cord circuit that is normally mechanically insensitive would receive mechanical input). I investigated this possibility and discovered population-specific regulation of transcripts. This included a mechanotransducer, Piezo2, which is upregulated in the small peptidergic subpopulation. Subsequent knockdown using Piezo2 siRNA reduced the number of mechanically sensitive afferents. These findings suggest that Piezo2 is necessary for mechanotransduction in injured afferents and could be responsible for induced neuropathic pain.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Adelman, Peterpca9@pitt.eduPCA9
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairKoerber, H.
Committee MemberDavis,
Committee MemberAlbers,
Committee MemberRoss,
Committee MemberOswald,
Committee MemberMendell,
Date: 30 September 2016
Date Type: Publication
Defense Date: 24 June 2016
Approval Date: 30 September 2016
Submission Date: 30 September 2016
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 120
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Neurobiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: nerve injury, DRG, regeneration, single cell qPCR, electrophysiology
Date Deposited: 30 Sep 2016 12:14
Last Modified: 15 Nov 2016 14:36


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