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Fang, M., Wang, Y., He, Q.H., Sun, Y.X., Deng, L.B., Wang, X.M. and Han, J.S. (2003), Glial cell
line-derived neurotrophic factor contributes to delayed inflammatory hyperalgesia in adjuvant rat
pain model. Neuroscience, 117 (3), 503-512.
Document type: Article Language: English Cited references: 57 Time cited: 21 Times self cited: 0
Abstract: Neurotrophic factors, such as nerve growth factor and brain-derived neurotrophic factor,
are members of the structurally related neurotrophin family that play important roles in pain
modulation. Although there are also indications for the involvement of glial cell line-derived
neurotrophic factor (GDNF), it is unclear whether and how GDNF is involved in inflammatory pain.
In the present study, we studied the expression pattern of GDNF in dorsal root ganglia (DRG) and
spinal cord, using confocal microscopy. We demonstrate that GDNF is well associated with
nonpeptidergic pain pathway and that GDNF could possibly be anterogradely transported from
DRG neurons to superficial spinal cord dorsal horn. We also studied the dynamic changes of GDNF
expression in rats during chronic inflammation using injection of complete Freund's adjuvant as a
model of chronic pain. We found that GDNF was down-regulated in both dorsal root ganglia and
spinal cords 2 weeks after arthritis induction. To assess the impact of this down-regulation on pain
transmission, we used a function-blocking antibody against GDNF delivered intrathecally in the
same chronic-pain animal models. Injection of this antibody to GDNF produced no immediate
effect, but decreased the delayed, bilateral hyperalgesia induced from a unilateral injection of
complete Freund's adjuvant. The effect of this antibody coincided with the downregulation of
GDNF immunoreactivity in response to inflammation, suggesting that GDNF supports biochemical
changes that contribute to hyperalgesia. (C) 2003 IBRO. Published by Elsevier Science Ltd. All
rights reserved.
Author Keywords: GDNF; pain pathway; nociception; arthritis; IB4
Keywords Plus: Anterograde Axonal-Transport; Midbrain Dopaminergic-Neurons; Sensory
Neurons; Primary Afferents; Spinal-Cord; Dorsal Horn; Substance-P; Immunocytochemical
Localization; Nervous-System; Ganglion-Cells
Reprint Address: Han, JS (reprint author), Peking Univ, Neurosci Res Inst, Hlth Sci Ctr, Beijing
100083, Peoples R China
Addresses:
1. Peking Univ, Neurosci Res Inst, Hlth Sci Ctr, Beijing 100083, Peoples R China
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