title: Selective innervation of NK1 receptor-lacking lamina I spinoparabrachial neurons by presumed nonpeptidergic Aδ nociceptors in the rat.
abstract: Fine myelinated (Aδ) nociceptors are responsible for fast, well-localised pain, but relatively little is known about their postsynaptic targets in the spinal cord, and therefore about their roles in the neuronal circuits that process nociceptive information. Here we show that transganglionically transported cholera toxin B subunit (CTb) labels a distinct set of afferents in lamina I that are likely to correspond to Aδ nociceptors, and that most of these lack neuropeptides. The vast majority of lamina I projection neurons can be retrogradely labelled from the lateral parabrachial area, and these can be divided into 2 major groups based on expression of the neurokinin 1 receptor (NK1r). We show that CTb-labelled afferents form contacts on 43% of the spinoparabrachial lamina I neurons that lack the NK1r, but on a significantly smaller proportion (26%) of those that express the receptor. We also confirm with electron microscopy that these contacts are associated with synapses. Among the spinoparabrachial neurons that received contacts from CTb-labelled axons, contact density was considerably higher on NK1r-lacking cells than on those with the NK1r. By comparing the density of CTb contacts with those from other types of glutamatergic bouton, we estimate that nonpeptidergic Aδ nociceptors may provide over half of the excitatory synapses on some NK1r-lacking spinoparabrachial cells. These results provide further evidence that synaptic inputs to dorsal horn projection neurons are organised in a specific way. Taken together with previous studies, they suggest that both NK1r(+) and NK1r-lacking lamina I projection neurons are directly innervated by Aδ nociceptive afferents.
authors.affiliation: Institute of Neuroscience and Psychology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Najma
authors.initials: N
authors.lastname: Baseer
authors.affiliation: Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Abdullah S
authors.initials: AS
authors.lastname: Al-Baloushi
authors.affiliation: Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. Electronic address: s.shehab@uaeu.ac.ae.
authors.forename: Safa A S
authors.initials: SA
authors.lastname: Shehab
authors.affiliation: Institute of Neuroscience and Psychology, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, UK. Electronic address: andrew.todd@glasgow.ac.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Todd
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002772:Cholera Toxin / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000648:ultrastructure; D009619:Nociceptors / Q000378:metabolism* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D066148:Spinal Cord Dorsal Horn / Q000166:cytology*; D013373:Substance P / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: D018040:Receptors, Neurokinin-1; D050599:Vesicular Glutamate Transport Protein 2; D013373:Substance P; D002772:Cholera Toxin; D015740:Calcitonin Gene-Related Peptide
keywords: Cholera toxin B subunit; Dorsal horn; Lamina I projection neuron; Spinal cord; Transganglionic tracing