title: Demyelination/remyelination and expression of interleukin-1β, substance P, nerve growth factor, and glial-derived neurotrophic factor during trigeminal neuropathic pain in rats.
abstract: The etiology of trigeminal neuropathic pain is not clear, but there is evidence that demyelination, expression of cytokines, neuropeptides, and neurotrophic factors are crucial contributors. In order to elucidate mechanisms underlying trigeminal neuropathic pain, we evaluated the time course of morphological changes in myelinated and unmyelinated trigeminal nerve fibers, expression of cytokine IL-1β, neuropeptide substance P (SP), nerve growth factor (NGF), and glial derived neurotrophic factor (GDNF) in peripheral and ganglion tissues, using a rat model of trigeminal neuropathic pain. Chronic constriction injury (CCI) of the infraorbital nerve (IoN), or a sham surgery, was performed. Mechanical allodynia was evaluated from day 3 to day 15 post-surgery. Trigeminal nerves were divided into 2 sections - distal to CCI and ganglion - for morphological analyses, immunohistochemistry (IL-1β, SP), and protein quantification by ELISA (NGF, GDNF). At early postoperative time points, decreased mechanical responses were observed, which were associated with demyelination, glial cell proliferation, increased immunoexpression of IL-1 β and SP, and impaired GDNF production. In the late postoperative period, mechanical allodynia was present with partial recovery of myelination, glial cell proliferation, and increased immunoreactivity of IL-1β and SP. Our data show that demyelination/remyelination processes are related to the development of pain behavior. IL-1β may have effects both in ganglia and nerves, while SP may be an important mediator at the nerve endings. Additionally, low levels of GDNF may produce impaired signaling, which may be involved in generation of pain.
authors.affiliation: Programa de Pós-Graduação em Patologia, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos, 6627-Pampulha, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Grazielle Mara Ferreira
authors.initials: GMF
authors.lastname: Costa
authors.affiliation: Departamento de Morfologia, Instituto de Ciências Biológicas (ICB), UFMG, Brazil.
authors.forename: Alexandre Penido
authors.initials: AP
authors.lastname: de Oliveira
authors.affiliation: Programa de Pós-Graduação em Patologia, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos, 6627-Pampulha, 31270-901 Belo Horizonte, MG, Brazil; Departamento de Morfologia, Instituto de Ciências Biológicas (ICB), UFMG, Brazil.
authors.forename: Patricia Massara
authors.initials: PM
authors.lastname: Martinelli
authors.affiliation: Departamento de Morfologia, Instituto de Ciências Biológicas (ICB), UFMG, Brazil.
authors.forename: Elizabeth Ribeiro
authors.initials: ER
authors.lastname: da Silva Camargos
authors.affiliation: Programa de Pós-Graduação em Patologia, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos, 6627-Pampulha, 31270-901 Belo Horizonte, MG, Brazil; Departamento de Patologia Geral, ICB/UFMG, Brazil.
authors.forename: Rosa Maria Esteves
authors.initials: RME
authors.lastname: Arantes
authors.affiliation: Programa de Pós-Graduação em Patologia, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos, 6627-Pampulha, 31270-901 Belo Horizonte, MG, Brazil; Departamento de Morfologia, Instituto de Ciências Biológicas (ICB), UFMG, Brazil. Electronic address: camila@icb.ufmg.br.
authors.forename: Camila Megale
authors.initials: CM
authors.lastname: de Almeida-Leite
mesh_terms: D000818:Animals; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000648:ultrastructure; D020932:Nerve Growth Factor / Q000378:metabolism*; D017208:Rats, Wistar; D013373:Substance P / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000378:metabolism / Q000648:ultrastructure; D014276:Trigeminal Nerve / Q000378:metabolism; D020433:Trigeminal Nerve Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D053583:Interleukin-1beta; D013373:Substance P; D020932:Nerve Growth Factor
keywords: Cytokine; Glial derived neurotrophic factor; Myelin; Nerve growth factor; Neuropeptide; Pain; Trigeminal nerve