Anti-NGF treatment can reduce chronic neuropathic pain by changing peripheral mediators and brain activity in rats

Autor(es)

da Silva, Joyce T. ^{[1, 2]} ; Evangelista, Bianca G. ^[1] ; Venega, Rafael A. G. ^[1] ; Seminowicz, David A. ^[2] ; Chacur, Marucia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci 3, Dept Anat, Sao Paulo - Brazil

^[2] Univ Maryland, Sch Dent, Dept Neural & Pain Sci, Room 8404, 650 W Baltimore St, Baltimore, MD 21201 - USA

• Tipo de documento: Artigo Científico
• Fonte: Behavioural Pharmacology; v. 30, n. 1, p. 79-88, FEB 2019.
• Citações Web of Science: 0

Resumo

Neuropathic pain is driven by abnormal peripheral and central processing, and treatments are insufficiently effective. Antibodies against nerve growth factor (anti-NGF) have been investigated as a potent analgesic treatment for numerous conditions. However, the peripheral and brain effects of anti-NGF in neuropathic pain remain unknown. We examined the effectiveness of anti-NGF in reducing chronic pain by local administration in a rat model of sciatic constriction injury (CCI). NGF and substance P in the dorsal root ganglion (DRG) and spinal cord were evaluated. Neuronal activation was measured using c-Fos in the anterior cingulate cortex and ventrolateral periaqueductal gray. At 14 days after CCI, anti-NGF promoted a significant dose-dependent improvement in mechanical threshold, thermal withdrawal latency, and cold sensitivity, lasting for 5 h. NGF upregulation in the DRG and spinal cord after CCI was decreased by anti-NGF, while substance P was increased only in the DRG, and the treatment reduced it. Anti-NGF induced a significant reduction of neuronal activation in the anterior cingulate cortex, but not in the ventrolateral periaqueductal gray. This study provides the first evidence of the anti-NGF effects on brain activity. Thus, our findings suggest that anti-NGF improves chronic neuropathic pain, acting directly on peripheral sensitization and indirectly on central sensitization. Copyright (c) 2018 Wolters Kluwer Health, Inc. All rights reserved. (AU)

• Processo FAPESP: 12/24408-6 - Ressonância magnética e ativação neuronal supraespinhal em modelo de dor neuropática crônica em ratos
• Beneficiário: Joyce Teixeira da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto