Anti-NGF treatment can reduce chronic neuropathic pain by changing peripheral mediators and brain activity in rats
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.
Keywords: anterior cingulate cortex; anti-nerve growth factor; nerve growth factor; neuropathic pain; periaqueductal gray; rat; substance P
Document Type: Research Article
Affiliations: 1: Department of Neural and Pain Sciences, School of Dentistry, University of Maryland, Baltimore, USA, Department of Anatomy, Institute of Biomedical Science-III, University of Sao Paulo, Sao Paulo, Brazil 2: Department of Anatomy, Institute of Biomedical Science-III, University of Sao Paulo, Sao Paulo, Brazil 3: Department of Neural and Pain Sciences, School of Dentistry, University of Maryland, Baltimore, USA
Publication date: 01 February 2019
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