title: Neurochemical characterization of insulin receptor-expressing primary sensory neurons in wild-type and vanilloid type 1 transient receptor potential receptor knockout mice.
abstract: The insulin receptor (IR) is expressed by a subpopulation of primary sensory neurons (PSN), including a proportion of cells expressing the nociceptive transducer vanilloid type 1 transient receptor potential receptor (TRPV1). Recent data suggest functional links between the IR and other receptors, including TRPV1, which could be involved in the development of PSN malfunctions in pathological insulin secretion. Here we used combined immunohistochemical labelling on sections from L4-5 dorsal root ganglia of wild-type (WT) and TRPV1 knockout (KO) mice to examine the neurochemical properties of IR-expressing PSN and the possible effect of deletion of TRPV1 on those characteristics. We found that antibodies raised against the high-molecular-weight neurofilament (NF-200) and the neurofilament protein peripherin distinguished between small and large neurons. We also found that the IR was expressed predominantly by the small peripherin-immunopositive cells both in the WT and in the KO animals. IR expression, however, did not show any preference between the major subpopulations of the small cells, the calcitonin gene-related peptide (CGRP)-expressing and Bandeiraea simplicifolia isolectin B4 (IB4)-binding neurons, either in the WT or in the KO mice. Nevertheless, a significant proportion of the IR-expressing cells also expressed TRPV1. Comparison of the staining pattern of these markers showed no difference between WT and KO animals. These findings indicate that the majority of the IR-expressing PSN are small neurons, which are considered as nociceptive cells. Furthermore, these data show that deletion of the TRPV1 gene does not induce any additional changes in neurochemical phenotype of nociceptive PSN.
authors.affiliation: Department of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, Chelsea and Westminster Hospital, London, SW10 9NH United Kingdom.
authors.forename: Djalil
authors.initials: D
authors.lastname: Baiou
authors.forename: Peter
authors.initials: P
authors.lastname: Santha
authors.forename: Antonio
authors.initials: A
authors.lastname: Avelino
authors.forename: Ana
authors.initials: A
authors.lastname: Charrua
authors.forename: Timea
authors.initials: T
authors.lastname: Bacskai
authors.forename: Klara
authors.initials: K
authors.lastname: Matesz
authors.forename: Francisco
authors.initials: F
authors.lastname: Cruz
authors.forename: Istvan
authors.initials: I
authors.lastname: Nagy
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D064531:Peripherins; D011972:Receptor, Insulin / Q000378:metabolism*; D018709:Statistics, Nonparametric; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D064531:Peripherins; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C051774:neurofilament protein H; D011972:Receptor, Insulin; D015740:Calcitonin Gene-Related Peptide