Preprotachykinin A (PPTA) is expressed by a distinct population of excitatory neurons in the mouse superficial spinal dorsal horn including cells that respond to noxious and pruritic stimuli

Gutierrez-Mecinas, M. , Bell, A. M. , Marin, A., Taylor, R., Boyle, K. A., Furuta, T., Watanabe, M., Polgár, E. and Todd, A. J. (2017) Preprotachykinin A (PPTA) is expressed by a distinct population of excitatory neurons in the mouse superficial spinal dorsal horn including cells that respond to noxious and pruritic stimuli. Pain, 158(3), pp. 440-456. (doi: 10.1097/j.pain.0000000000000778) (PMID:27902570) (PMCID:PMC5302415)

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Abstract

The superficial dorsal horn, which is the main target for nociceptive and pruritoceptive primary afferents, contains a high density of excitatory interneurons. Our understanding of their roles in somatosensory processing has been restricted by the difficulty of distinguishing functional populations among these cells. We recently defined three non-overlapping populations among the excitatory neurons, based on the expression of neurotensin, neurokinin B (NKB) and gastrin-releasing peptide (GRP). Here we identify and characterise another population: neurons that express the tachykinin peptide substance P. We show with immunocytochemistry that its precursor protein (preprotachykinin A, PPTA) can be detected in ~14% of lamina I-II neurons, and these are concentrated in the outer part of lamina II. Over 80% of the PPTA-positive cells lack the transcription factor Pax2 (which determines an inhibitory phenotype), and these account for ~15% of the excitatory neurons in this region. They are different from the neurotensin, NKB or GRP neurons, although many of them contain somatostatin, which is widely expressed among superficial dorsal horn excitatory interneurons. We show that many of these cells respond to noxious thermal and mechanical stimuli, and to intradermal injection of pruritogens. Finally, we demonstrate that these cells can also be identified in a knock-in Cre mouse line (Tac1Cre), although our findings suggest that there is an additional population of neurons that transiently express PPTA. This population of substance P-expressing excitatory neurons is likely to play an important role in transmission of signals that are perceived as pain and itch.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Boyle, Dr Kieran and Bell, Mr Andrew and Beresford-Polgar, Dr Erika and Todd, Professor Andrew and Gutierrez-Mecinas, Dr Maria
Authors: Gutierrez-Mecinas, M., Bell, A. M., Marin, A., Taylor, R., Boyle, K. A., Furuta, T., Watanabe, M., Polgár, E., and Todd, A. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:Pain
Publisher:Lippincott Williams & Wilkins
ISSN:0304-3959
ISSN (Online):1872-6623
Published Online:25 November 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Pain 158(3):440-456
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
644161Defining pain circuitry in health and diseaseAndrew ToddWellcome Trust (WELLCOME)102645/Z/13/ZINP - CENTRE FOR NEUROSCIENCE
627371Spinal inhibitory interneurons that suppress itchAndrew ToddMedical Research Council (MRC)MR/L003430/1INP - CENTRE FOR NEUROSCIENCE
689031The role of NPY-containing inhibitory interneurons in spinal pain pathwaysAndrew ToddBiotechnology and Biological Sciences Research Council (BBSRC)BB/N006119/1INP - CENTRE FOR NEUROSCIENCE