RGD Reference Report - The thalidomide analgesic effect is associated with differential TNF-alpha receptor expression in the dorsal horn of the spinal cord as studied in a rat model of neuropathic pain.

General

The thalidomide analgesic effect is associated with differential TNF-alpha receptor expression in the dorsal horn of the spinal cord as studied in a rat model of neuropathic pain.
Authors:	Andrade, P Visser-Vandewalle, V Del Rosario, JS Daemen, MA Buurman, WA Steinbusch, HW Hoogland, G
Citation:	Andrade P, etal., Brain Res. 2012 Apr 23;1450:24-32. doi: 10.1016/j.brainres.2012.02.033. Epub 2012 Feb 22.
RGD ID:	7245944
Pubmed:	PMID:22425187 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.brainres.2012.02.033 (Journal Full-text)
The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is well recognized as a key player in nociceptive signaling. Yet, therapeutic capitalization of this knowledge requires a better understanding of how TNF receptors (TNFR) contribute to pain. To address this question, we studied TNFR expression in the chronic sciatic nerve constriction (CCI) model of neuropathic pain. CCI and sham operated rats received two subcutaneous injections (one immediately after surgery, the other on postoperative day 5) containing either saline, GABA-reuptake inhibitor (NO-711), insulin-like growth factor-1 (IGF-1), ZVAD or thalidomide. Mechanical (using von Frey filaments) and thermal hypersensitivity (Hargreaves test) were assessed preoperatively and weekly during the first four postoperative weeks. Spinal cord dorsal horn samples were collected from animals that were sacrificed at 2 weeks and 4 weeks after surgery, and analyzed for TNFR1 and TNFR2 mRNA levels by qPCR and protein levels by Western blot. Compared to saline, all applied drug treatments resulted in a faster recovery from mechanical and thermal hypersensitivity, yet in a potency order of thalidomide>ZVAD=IGF-1>NO-711. CCI resulted in increased TNFR1 and TNFR2 mRNA and protein levels in the ipsilateral dorsal horn. Thalidomide was the only treatment that attenuated these increases. Finally, animals that showed a poor behavioral recovery were characterized by a significantly higher TNFR1/TNFR2 mRNA ratio. These data show that differential expression of TNFR in the dorsal horn is associated with recovery from pain in this model and suggest that the analgesic effects of thalidomide may act via this mechanism.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Sciatica	treatment	ISO	Tnfrsf1b (Rattus norvegicus)	7245944; 7245944		RGD
Sciatica	treatment	IDA		7245944		RGD

Objects Annotated

Genes (Rattus norvegicus)

Tnfrsf1b (TNF receptor superfamily member 1B)

Genes (Mus musculus)

Tnfrsf1b (tumor necrosis factor receptor superfamily, member 1b)

Genes (Homo sapiens)

TNFRSF1B (TNF receptor superfamily member 1B)

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The thalidomide analgesic effect is associated with differential TNF-alpha receptor expression in the dorsal horn of the spinal cord as studied in a rat model of neuropathic pain.