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Brain-derived neurotrophic factor contributes to spinal long-term potentiation and mechanical hypersensitivity by activation of spinal microglia in rat.
Brain Behav Immun. 2011 Feb; 25(2):322-34.BB

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 naïve 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.

Authors+Show Affiliations

Pain Research Center and Department of Physiology, Zhongshan Medicine School of Sun Yat-sen University, 510089 Guangzhou, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20933591

Citation

Zhou, Li-Jun, et al. "Brain-derived Neurotrophic Factor Contributes to Spinal Long-term Potentiation and Mechanical Hypersensitivity By Activation of Spinal Microglia in Rat." Brain, Behavior, and Immunity, vol. 25, no. 2, 2011, pp. 322-34.
Zhou LJ, Yang T, Wei X, et al. Brain-derived neurotrophic factor contributes to spinal long-term potentiation and mechanical hypersensitivity by activation of spinal microglia in rat. Brain Behav Immun. 2011;25(2):322-34.
Zhou, L. J., Yang, T., Wei, X., Liu, Y., Xin, W. J., Chen, Y., Pang, R. P., Zang, Y., Li, Y. Y., & Liu, X. G. (2011). Brain-derived neurotrophic factor contributes to spinal long-term potentiation and mechanical hypersensitivity by activation of spinal microglia in rat. Brain, Behavior, and Immunity, 25(2), 322-34. https://doi.org/10.1016/j.bbi.2010.09.025
Zhou LJ, et al. Brain-derived Neurotrophic Factor Contributes to Spinal Long-term Potentiation and Mechanical Hypersensitivity By Activation of Spinal Microglia in Rat. Brain Behav Immun. 2011;25(2):322-34. PubMed PMID: 20933591.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brain-derived neurotrophic factor contributes to spinal long-term potentiation and mechanical hypersensitivity by activation of spinal microglia in rat. AU - Zhou,Li-Jun, AU - Yang,Tao, AU - Wei,Xiao, AU - Liu,Yong, AU - Xin,Wen-Jun, AU - Chen,Yuan, AU - Pang,Rui-Ping, AU - Zang,Ying, AU - Li,Yong-Yong, AU - Liu,Xian-Guo, Y1 - 2010/10/08/ PY - 2010/08/01/received PY - 2010/09/24/revised PY - 2010/09/30/accepted PY - 2010/10/12/entrez PY - 2010/10/12/pubmed PY - 2011/5/5/medline SP - 322 EP - 34 JF - Brain, behavior, and immunity JO - Brain Behav. Immun. VL - 25 IS - 2 N2 - 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 naïve 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. SN - 1090-2139 UR - https://www.unboundmedicine.com/medline/citation/20933591/Brain_derived_neurotrophic_factor_contributes_to_spinal_long_term_potentiation_and_mechanical_hypersensitivity_by_activation_of_spinal_microglia_in_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0889-1591(10)00506-4 DB - PRIME DP - Unbound Medicine ER -