title: Preprotachykinin A 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.
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 3 nonoverlapping populations among the excitatory neurons, based on the expression of neurotensin, neurokinin B, and gastrin-releasing peptide. 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, neurokinin B, or gastrin-releasing peptide 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 (Tac1), 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 the transmission of signals that are perceived as pain and itch.
authors.affiliation: Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Gutierrez-Mecinas
authors.affiliation: Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, United Kingdom.|School of Veterinary Medicine, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Bell
authors.affiliation: Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Alina
authors.initials: A
authors.lastname: Marin
authors.affiliation: Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Taylor
authors.affiliation: Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Kieran A
authors.initials: KA
authors.lastname: Boyle
authors.affiliation: Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Furuta
authors.affiliation: Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Erika
authors.initials: E
authors.lastname: Polgár
authors.affiliation: Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Todd
mesh_terms: D000818:Animals; D005260:Female; D019886:Gastrin-Releasing Peptide / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D015287:Neurokinin B / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D009496:Neurotensin / Q000235:genetics / Q000378:metabolism; D051762:PAX2 Transcription Factor / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D018689:Sensory System Agents / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology; D066148:Spinal Cord Dorsal Horn / Q000166:cytology* / Q000378:metabolism; D015320:Tachykinins / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D051762:PAX2 Transcription Factor; C551986:PAX2 protein, rat; D011498:Protein Precursors; D018689:Sensory System Agents; C118623:Slc32a1 protein, rat; D015320:Tachykinins; D025521:Tumor Suppressor Proteins; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C044206:preprotachykinin; D009496:Neurotensin; D019886:Gastrin-Releasing Peptide; D015287:Neurokinin B