RT Journal Article
T1 Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling.
A1 Cobos, Enrique J
A1 Nickerson, Chelsea A
A1 Gao, Fuying
A1 Chandran, Vijayendran
A1 Bravo-Caparros, Inmaculada
A1 Gonzalez-Cano, Rafael
A1 Riva, Priscilla
A1 Andrews, Nick A
A1 Latremoliere, Alban
A1 Seehus, Corey R
A1 Perazzoli, Gloria
A1 Nieto, Francisco R
A1 Joller, Nicole
A1 Painter, Michio W
A1 Ma, Chi Him Eddie
A1 Omura, Takao
A1 Chesler, Elissa J
A1 Geschwind, Daniel H
A1 Coppola, Giovanni
A1 Rangachari, Manu
A1 Woolf, Clifford J
A1 Costigan, Michael
K1 T cells
K1 TrpV1
K1 WCGNA
K1 cold allodynia
K1 gene expression
K1 immune system
K1 macrophages
K1 neuropathic pain
K1 tactile allodynia
K1 transcript profiling
AB Chronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia) is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia in a model of partial nerve injury, and this temporal divergence was associated with major differences in global gene expression in innervating dorsal root ganglia. Transcripts whose expression change correlates with the onset of cold allodynia were nociceptor related, whereas those correlating with tactile hypersensitivity were immune cell centric. Ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity, whereas depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain incorporates reactive processes of sensory neurons and immune cells, each leading to distinct forms of hypersensitivity, potentially allowing drug development targeted to each pain type.
PB Cell Press
YR 2018
FD 2018-01-02
LK http://hdl.handle.net/10668/12070
UL http://hdl.handle.net/10668/12070
LA en
NO Cobos EJ, Nickerson CA, Gao F, Chandran V, Bravo-Caparrós I, González-Cano R, et al. Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling. Cell Rep. 2018 Jan 30;22(5):1301-1312.
NO This study was supported by NIH grants R01NS074430 (M.C.), R01NS58870, and R37NS039518 (C.J.W.); the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (C.J.W., G.C., and D.G.); NINDS Informatics Center for Neurogenetics and Neurogenomics (P30 NS062691) (F.G. and G.C.); Neurodevelopmental Behavior Core, grant CHB IDDRC, 1U54HD090255 (N.A.A.); and grants SAF2013-47481P and SAF2016-80540-R from the Spanish Ministry of Economy and Competitiveness (MINECO) and the European Regional Development Fund (FEDER) (E.J. Cobos). E.J. Cobos was supported by the Research Program of the University of Granada. I.B.-C. was supported by an FPU grant from MINECO. R.G.C. was supported by the Alfonso Martin Escudero fellowship. F.R.N. was supported by a Juan de la Cierva postdoctoral grant from MINECO. M.R. was supported by a Junior-1 salary support award from the Fonds de recherche du Québec - Santé (FRQS).
DS RISalud
RD Apr 18, 2025