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Brain-derived neurotrophic factor contributes to spinal long-term potentiation and mechanical hypersensitivity by activation of spinal microglia in rat
- Source :
- Brain, behavior, and immunity. 25(2)
- Publication Year :
- 2010
-
Abstract
- It has been shown that following peripheral nerve injury brain-derived neurotrophic factor (BDNF) released by activated microglia contributes to neuropathic pain, but whether BDNF affects the function of microglia is still unknown. In the present work we found that spinal application of BDNF, which induced long-term potentiation (LTP) of C-fiber evoked field potentials, activated spinal microglia in naive animals, while pretreatment with microglia inhibitor minocycline blocked BDNF-induced LTP. In addition, following LTP induction by BDNF, both phosphorylated Src-family kinases (p-SFKs) and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) were up-regulated only in spinal microglia but not in neurons and astrocytes, whilst spinal application of SFKs inhibitor (PP2 or SU6656) or p38 MAPK inhibitor (SB203580) blocked BDNF-induced LTP and suppressed microglial activation. As spinal LTP at C-fiber synapses is considered to underlie neuropathic pain, we subsequently examined whether BDNF may contribute to mechanical hypersensitivity by activation of spinal microglia using spared nerve injury (SNI) model. Following SNI BDNF and TrkB receptor were up-regulated mainly in dorsal horn neurons and in activated microglia, and p-SFKs and p-p38 MAPK were increased exclusively in microglia. Intrathecal injection of BDNF scavenger TrkB-Fc starting before SNI, which prevented the behavioral sign of neuropathic pain, suppressed both microglial activation and the up-regulation of p-SFKs and p-p38 MAPK produced by SNI. Thus, the increased BDNF/TrkB signaling in spinal dorsal horn may contribute to neuropathic pain by activation of microglia following peripheral nerve injury and inhibition of SFKs or p38 MAPK may selectively inhibit microglia in spinal dorsal horn.
- Subjects :
- Male
SNi
Immunology
Long-Term Potentiation
Minocycline
Tropomyosin receptor kinase B
p38 Mitogen-Activated Protein Kinases
Rats, Sprague-Dawley
Behavioral Neuroscience
Neurotrophic factors
LTP induction
Medicine
Animals
Receptor, trkB
Injections, Spinal
Brain-derived neurotrophic factor
Neurons
Nerve Fibers, Unmyelinated
Microglia
Behavior, Animal
Endocrine and Autonomic Systems
business.industry
Brain-Derived Neurotrophic Factor
Long-term potentiation
Immunohistochemistry
Anti-Bacterial Agents
Electrophysiological Phenomena
Rats
Up-Regulation
medicine.anatomical_structure
src-Family Kinases
nervous system
Spinal Cord
Astrocytes
Neuropathic pain
Synapses
Neuralgia
business
Neuroscience
Signal Transduction
Subjects
Details
- ISSN :
- 10902139
- Volume :
- 25
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Brain, behavior, and immunity
- Accession number :
- edsair.doi.dedup.....ea0fe3d3645073df8b387e31475f3103