Universität zu Köln

Andrade, Pablo ORCID: 0000-0002-2596-7301, Hoogland, Govert, Del Rosario, John S., Steinbusch, Harry W., Visser-Vandewalle, Veerle and Daemen, Marc A. (2014). Tumor Necrosis Factor-alpha Inhibitors Alleviation of Experimentally Induced Neuropathic Pain is Associated With Modulation of TNF Receptor Expression. J. Neurosci. Res., 92 (11). S. 1490 - 1499. HOBOKEN: WILEY-BLACKWELL. ISSN 1097-4547

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Abstract

Inflammation plays a key role in the development of sensitization after peripheral nerve damage. We recently demonstrated that tumor necrosis factor-a receptor (TNFR) levels in the spinal cord correlate with pain sensation in herniated disc patients in a rat chronic constriction injury (CCI) model. By using the sciatic nerve CCI model, we studied the effect of anti-TNF-alpha treatment on recovery from hypersensitivity and TNFR expression in the dorsal root ganglion (DRG) and dorsal horn (DH). Experimental groups consisted of sham-operated and CCI-operated rats that received two s.c. injections (one immediately after surgery, the other 5 days later), both containing saline, etanercept (3 mg/kg body weight), or infliximab (10 mg/kg body weight). Mechanical allodynia (with von Frey filaments) and thermal hyperalgesia (Hargreaves test) were assessed preoperatively and weekly during the first 4 postoperative weeks. DRG and DH samples were collected 2 and 4 weeks after surgery and analyzed for TNFR1 and TNFR2 protein levels by Western blotting and analyzed for mRNA levels by quantitative real-time polymerase chain reaction. Anti-TNF-alpha treatment resulted in a significant alleviation of pain. TNFR levels were increased five-to sixfold in CCI rats compared with sham controls. Both treatments significantly diminished these increased levels. Treated animals that showed a >= 50% alleviation of pain exhibited a significantly reduced TNF R1/R2 mRNA ratio compared with treated animals that recovered less well. These results demonstrate that attenuation of TNFR expression is associated with recovery from nerve injury and suggest that this may be one of the working mechanisms of anti-TNF therapies. (C) 2014 Wiley Periodicals, Inc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Andrade, Pablo UNSPECIFIED orcid.org/0000-0002-2596-7301 UNSPECIFIED Hoogland, Govert UNSPECIFIED UNSPECIFIED UNSPECIFIED Del Rosario, John S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Steinbusch, Harry W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Visser-Vandewalle, Veerle UNSPECIFIED UNSPECIFIED UNSPECIFIED Daemen, Marc A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-425236
DOI:	10.1002/jnr.23432
Journal or Publication Title:	J. Neurosci. Res.
Volume:	92
Number:	11
Page Range:	S. 1490 - 1499
Date:	2014
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	1097-4547
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHRONIC CONSTRICTION INJURY; DORSAL-ROOT GANGLIA; RAT SCIATIC-NERVE; CENTRAL SENSITIZATION; SPINAL-CORD; MECHANICAL ALLODYNIA; SENSORY NEURONS; PERSISTENT PAIN; DOUBLE-BLIND; FOLLOW-UP Multiple languages Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42523