title: A reversible functional sensory neuropathy model.
abstract: Small-fiber neuropathy was induced in young adult mice by intraperitoneal injection of resiniferatoxin (RTX), a TRPV1 agonist. At day 7, RTX induced significant thermal and mechanical hypoalgesia. At day 28, mechanical and thermal nociception were restored. No nerve degeneration in skin was observed and unmyelinated nerve fiber morphology and density in sciatic nerve were unchanged. At day 7, substance P (SP) was largely depleted in dorsal root ganglia (DRG) neurons, although calcitonin gene-related peptide (CGRP) was only moderately depleted. Three weeks after, SP and CGRP expression was restored in DRG neurons. At the same time, CGRP expression remained low in intraepidermal nerve fibers (IENFs) whereas SP expression had improved. In summary, RTX induced in our model a transient neuropeptide depletion in sensory neurons without nerve degeneration. We think this model is valuable as it brings the opportunity to study functional nerve changes in the very early phase of small fiber neuropathy. Moreover, it may represent a useful tool to study the mechanisms of action of therapeutic strategies to prevent sensory neuropathy of various origins.
authors.affiliation: EA 6309 - Schools of Medicine and Pharmacy - University of Limoges, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Danigo
authors.affiliation: EA 6309 - Schools of Medicine and Pharmacy - University of Limoges, France; Service de Neurologie, Centre de référence national "neuropathies périphériques rares" - CHU Limoges, 87042 Limoges Cedex, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Magy
authors.affiliation: EA 6309 - Schools of Medicine and Pharmacy - University of Limoges, France; Service de Neurologie, Centre de référence national "neuropathies périphériques rares" - CHU Limoges, 87042 Limoges Cedex, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Richard
authors.affiliation: EA 6309 - Schools of Medicine and Pharmacy - University of Limoges, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Sturtz
authors.affiliation: EA 6309 - Schools of Medicine and Pharmacy - University of Limoges, France; Service de Neurologie, Centre de référence national "neuropathies périphériques rares" - CHU Limoges, 87042 Limoges Cedex, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Funalot
authors.affiliation: EA 6309 - Schools of Medicine and Pharmacy - University of Limoges, France. Electronic address: claire.demiot@unilim.fr.
authors.forename: Claire
authors.initials: C
authors.lastname: Demiot
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004224:Diterpenes; D004817:Epidermis / Q000294:innervation; D005727:Ganglia, Spinal / Q000473:pathology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology; D009437:Neuralgia / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D059225:Nociception; D010812:Physical Stimulation; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000473:pathology; D050916:TRPV Cation Channels / Q000819:agonists; D014110:Touch
chemical_list: D004224:Diterpenes; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C024353:resiniferatoxin
keywords: Calcitonin-gene related peptide; Intraepidermal nerve fiber; Nociception; Resiniferatoxin; Small-fiber neuropathy; Substance P