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Neuroinflammation evoked mechanisms for neuropathic itch in the spared nerve injury mouse model of neuropathic pain.
- Source :
-
Neuropharmacology [Neuropharmacology] 2024 Nov 15; Vol. 259, pp. 110120. Date of Electronic Publication: 2024 Aug 17. - Publication Year :
- 2024
-
Abstract
- A large portion of neuropathic pain suffering patients may also concurrently experience neuropathic itch, with a negative impact on the quality of life. The limited understanding of neuropathic itch and the low efficacy of current anti-itch therapies dictate the urgent need of a better comprehension of molecular mechanisms involved and development of relevant animal models. This study was aimed to characterize the itching phenotype in a model of trauma-induced peripheral neuropathy, the spared nerve injury (SNI), and the molecular events underlying the overlap with the nociceptive behavior. SNI mice developed hyperknesis and spontaneous itch 7-14 days after surgery that was prevented by gabapentin treatment. Itch was associated with pain hypersensitivity, loss of intraepidermal nerve fiber (IENF) density and increased epidermal thickness. In coincidence with the peak of scratching behavior, SNI mice showed a spinal overexpression of IBA1 and GFAP, microglia and astrocyte markers respectively. An increase of the itch neuropeptide B-type natriuretic peptide (BNP) in NeuN+ cells, of its downstream effector interleukin 17 (IL17) along with increased pERK1/2 levels occurred in the spinal cord dorsal horn and DRG. A raise in BNP and IL17 was also detected at skin level. Stimulation of HaCat cells with conditioned medium from BV2-stimulated SH-SY5Y cells produced a dramatic reduction of HaCat cell viability. This study showed that SNI mice might represent a model for neuropathic itch and pain. Collectively, our finding suggest that neuropathic itch might initiate at spinal level, then affecting skin epidermis events, through a glia-mediated neuroinflammation-evoked BNP/IL17 mechanism.<br />Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare.<br /> (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Subjects :
- Animals
Mice
Male
Humans
Gabapentin pharmacology
Interleukin-17 metabolism
Mice, Inbred C57BL
Ganglia, Spinal metabolism
Ganglia, Spinal drug effects
Ganglia, Spinal pathology
HaCaT Cells
Microglia metabolism
Microglia drug effects
Hyperalgesia metabolism
Microfilament Proteins metabolism
Spinal Cord Dorsal Horn metabolism
Spinal Cord Dorsal Horn drug effects
Calcium-Binding Proteins
Pruritus metabolism
Pruritus pathology
Neuralgia metabolism
Neuralgia etiology
Disease Models, Animal
Neuroinflammatory Diseases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7064
- Volume :
- 259
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 39159835
- Full Text :
- https://doi.org/10.1016/j.neuropharm.2024.110120