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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/49592

Title: Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling
Authors: Cobos del Moral, Enrique J.
Nickerson, Chelsea A.
Gao, Fuying
Chandran, Vijayendran
Bravo-Caparros, Inmaculada
González-Cano, Rafael
Riva, Priscilla
Andrews, Nick A.
Latremoiere, Alban
Seehus, Corey R.
Perazzoli, Gloria
Nieto López, Francisco Rafael
Joller, Nicole
Painter, Michio W.
Ma, Chi Him Eddie
Omura, Takao
Chesler, Elissa J.
Geschwind, Daniel H.
Coppola, Giovanni
Rangachari, Manu
Woolf, Clifford J.
Costigan, Michael
Issue Date: Jan-2018
Abstract: 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.
Sponsorship: 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).
Publisher: Cell Press
Keywords: Neuropathic pain
Pain macrophages
T cells
Immune system
Tactile allodynia
Cold allodynia
Gene expression
Transcript profiling
URI: http://hdl.handle.net/10481/49592
ISSN: 2211-1247
Rights : Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
Citation: Cobos, E.J.; et al. Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling. Cell Reports, 22(5): 1301-1312 (2018). [http://hdl.handle.net/10481/49592]
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