Universität zu Köln

Crosby, Nathan D., Zaucke, Frank, Kras, Jeffrey V., Dong, Ling, Luo, Z. David and Winkelstein, Beth A. (2015). Thrombospondin-4 and excitatory synaptogenesis promote spinal sensitization after painful mechanical joint injury. Exp. Neurol., 264. S. 111 - 121. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1090-2430

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Abstract

Facet joint injury induces persistent pain that may be maintained by structural plasticity in the spinal cord. Astrocyte-derived thrombospondins, especially thrombospondin-4 (TSP4), have been implicated in synaptogenesis and spinal sensitization in neuropathic pain, but the TSP4 response and its relationship to synaptic changes in the spinal cord have not been investigated for painful joint injury. This study investigates the role of TSP4 in the development and maintenance of persistent pain following injurious facet joint distraction in rats and tests the hypothesis that excitatory synaptogenesis contributes to such pain. Painful facet joint loading induces dorsal horn excitatory synaptogenesis along with decreased TSP4 in the DRG and increased astrocytic release of TSP4 in the spinal cord, all of which parallel the time course of sustained tactile allodynia. Blocking injury-induced spinal TSP4 expression with antisense oligonucleotides or reducing TSP4 activity at its neuronal receptor in the spinal cord with gabapentin treatment both attenuate the allodynia and dorsal horn synaptogenesis that develop after painful facet joint loading. Increased spinal TSP4 also facilitates the development of allodynia and spinal hyperexcitability, even after non-painful physiological loading of the facet joint These results suggest that spinal TSP4 plays an important role in the development and maintenance of persistent joint-mediated pain by inducing excitatory synaptogenesis and facilitating the transduction of mechanical loading of the facet joint that leads to spinal hyperexcitability. (C) 2014 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Crosby, Nathan D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zaucke, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Kras, Jeffrey V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dong, Ling UNSPECIFIED UNSPECIFIED UNSPECIFIED Luo, Z. David UNSPECIFIED UNSPECIFIED UNSPECIFIED Winkelstein, Beth A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-413905
DOI:	10.1016/j.expneurol.2014.11.015
Journal or Publication Title:	Exp. Neurol.
Volume:	264
Page Range:	S. 111 - 121
Date:	2015
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication:	SAN DIEGO
ISSN:	1090-2430
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FACET JOINT; NEUROPATHIC PAIN; DORSAL-HORN; NEURONAL HYPEREXCITABILITY; ASTROCYTIC ACTIVATION; UP-REGULATION; CORD; RAT; EXPRESSION; CONTRIBUTES Multiple languages Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41390