title: Peripheral nerve injury induces loss of nociceptive neuron-specific Gαi-interacting protein in neuropathic pain rat.
abstract: BACKGROUND
  Gαi-interacting protein (GINIP) is expressed specifically in dorsal root ganglion (DRG) neurons and functions in modulation of peripheral gamma-aminobutyric acid B receptor (GBR). Genetic deletion of GINIP leads to impaired responsiveness to GBR agonist-mediated analgesia in rodent. It is, however, not defined whether nerve injury changes GINIP expression.
  
  
  RESULTS
  Immunolabeling with validated antibody revealed GINIP expression in ~40% of total lumbar DRG neurons in normal adult rats. GINIP immunoreactivity was detected in ~80% of IB4-positive (nonpeptidergic) and ~30% of CGRP-positive (peptidergic) neurons. GINIP immunoreactivity in the spinal cord dorsal horn was colabeled with IB4 and partially with CGRP. In addition, GINIP was expressed in DRG neurons immunopositive for GBR1, GBR2, Gαi(s), and Gαo and was also extensively colabeled with multiple nociceptive neuronal markers, including Trpv1, NaV1.7, CaV2.2α1b, CaV3.2α1b, TrkA, and Trek2. Peripheral nerve injury by L5 spinal nerve ligation significantly decreased the proportion of GINIP immunoreactivity-positive neurons from 40 ± 8.4% to 0.8 ± 0.1% (p < 0.01, mean ± SD, four weeks after spinal nerve ligation) and the total GINIP protein to 1.3% ± 0.04% of its basal level (p < 0.01, n = 6 animals in each group, two weeks after spinal nerve ligation) in the ipsilateral L5 DRGs.
  
  
  CONCLUSIONS
  Our results show that GINIP is predominantly expressed by small nonpeptidergic nociceptive neurons and that nerve injury triggers loss of GINIP expression. Signal transduction roles of GINIP may be diverse as it colabeled with various subgroups of nociceptive neurons. Future studies may investigate details of the signaling mechanism engaged by GINIP, as well as the pathophysiological significance of lost expression of GINIP in neuropathic pain.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA Department of Physiology, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Fischer
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA Zablocki Veterans Affairs Medical Center, Milwaukee, WI, USA.
authors.forename: Quinn H
authors.initials: QH
authors.lastname: Hogan
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA Zablocki Veterans Affairs Medical Center, Milwaukee, WI, USA hyu@mcw.edu qhogan@mcw.edu.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D019771:Axotomy; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009437:Neuralgia / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D009619:Nociceptors / Q000378:metabolism*; D059348:Peripheral Nerve Injuries / Q000378:metabolism / Q000473:pathology*; D017729:Presynaptic Terminals / Q000378:metabolism; D021381:Protein Transport; D017207:Rats, Sprague-Dawley
chemical_list: C000613071:GINIP protein, rat; D047908:Intracellular Signaling Peptides and Proteins
keywords: Dorsal root ganglion; Gαi-interacting protein; gamma-aminobutyric acid B receptor; neuropathic pain; peripheral nerve