Format

Send to

Choose Destination
Pain. 2008 Jul 31;137(3):507-19. Epub 2007 Nov 26.

TNF signaling contributes to the development of nociceptive sensitization in a tibia fracture model of complex regional pain syndrome type I.

Author information

1
Physical Medicine and Rehabilitation Service (117), Veterans Affairs Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304, USA.

Abstract

Tibia fracture in rats initiates a cascade of nociceptive, vascular, and bone changes resembling complex regional pain syndrome type I (CRPS I). Previous studies suggest that the pathogenesis of these changes is attributable to an exaggerated regional inflammatory response to injury. We postulated that the pro-inflammatory cytokine tumor necrosis factor alpha (TNF) might mediate the development of CRPS-like changes after fracture. RT-PCR and EIA assays were used to evaluate changes in TNF expression and content in skin, nerve, and bone after fracture. Bilateral hindpaw thickness, temperature, and nociceptive thresholds were determined, and bone microarchitecture was measured using microcomputed tomography. Lumbar spinal cord Fos immunostaining was performed for quantification of Fos positive neurons. After baseline testing, the distal tibia was fractured and the hindlimb casted for 4 weeks. The rats were subcutaneously injected either with a soluble TNF receptor type 1 (sTNF-R1, 5mg/kg/d) or saline every 3 days over 28 days and then were retested at 4 weeks post-fracture. Tibia fracture chronically upregulated TNF expression and protein levels in the hindpaw skin and sciatic nerve. After fracture the rats developed hindpaw mechanical allodynia and unweighting, which were reversed by sTNF-R1 treatment. Consistent with the behavioral data, spinal Fos increased after fracture and this effect was inhibited by sTNF-R1 treatment. Collectively, these data suggest that facilitated TNF signaling in the hindlimb is an important mediator of chronic regional nociceptive sensitization after fracture, but does not contribute to the hindlimb warmth, edema, and bone loss observed in this CRPS I model.

PMID:
18035493
PMCID:
PMC2529181
DOI:
10.1016/j.pain.2007.10.013
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wolters Kluwer Icon for PubMed Central
Loading ...
Support Center