title: Upregulation of Ih expressed in IB4-negative Aδ nociceptive DRG neurons contributes to mechanical hypersensitivity associated with cervical radiculopathic pain.
abstract: Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron's ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensitivity. Amongst nociceptive DRG neurons, a mechanically sensitive neuron, isolectin B4 negative Aδ-type (IB4(-) Aδ) DRG neuron displays spontaneous activity with hyperexcitability after chronic compression of cervical DRGs. Focal mechanical stimulation on somata of IB4(-) Aδ neuron induces abnormal hypersensitivity. Upregulated HCN1 and HCN3 channels and increased Ih current on this subset of primary nociceptors underlies the spontaneous activity together with neuronal mechanical hypersensitivity, which further contributes to the behavioral mechanical hypersensitivity associated with CRP. This study sheds new light on the functional plasticity of a specific subset of nociceptive DRG neurons to mechanical stimulation and reveals a novel mechanism that could underlie the mechanical hypersensitivity associated with cervical radiculopathy.
authors.affiliation: Institute of Neurosciences and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Da-Lu
authors.initials: DL
authors.lastname: Liu
authors.affiliation: Institute of Neurosciences and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Na
authors.initials: N
authors.lastname: Lu
authors.affiliation: Institute of Neurosciences and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Han
authors.affiliation: Institute of Neurosciences and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Rong-Gui
authors.initials: RG
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Cong
authors.affiliation: Institute of Neurosciences and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Rou-Gang
authors.initials: RG
authors.lastname: Xie
authors.affiliation: School of Clinical Medicine, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Zhang
authors.affiliation: Institute of Neurosciences and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an 710032, China.|Department of Anesthesiology, Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Kong
authors.affiliation: Institute of Neurosciences and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: San-Jue
authors.initials: SJ
authors.lastname: Hu
authors.affiliation: Institute of Neurosciences and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ceng
authors.initials: C
authors.lastname: Luo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000503:physiopathology*; D015870:Gene Expression; D016762:Genes, fos; D006930:Hyperalgesia / Q000209:etiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics*; D040542:Mechanotransduction, Cellular; D008564:Membrane Potentials; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D009437:Neuralgia / Q000209:etiology; D009619:Nociceptors / Q000378:metabolism*; D010766:Phosphorylation; D011843:Radiculopathy / Q000150:complications / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D051381:Rats; D015854:Up-Regulation
chemical_list: D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3