Journal
PAIN
Volume 138, Issue 1, Pages 47-60Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1016/j.pain.2007.11.004
Keywords
complex regional pain syndrome; tibia fracture; NGF; neuropathic pain; c-Fos immunoreactivity; microCT scanning; cytokines
Categories
Funding
- National Institutes of Health [GM65345, DK67197]
Ask authors/readers for more resources
Tibia fracture in rats evokes chronic hindpaw warmth, edema, allodynia, and regional osteopenia resembling the clinical characteristics of patients with complex regional pain syndrome type I (CRPS I). Nerve growth factor (NGF) has been shown to support nociceptive and other types of changes found in neuropathic pain models. We hypothesized that anti-NGF antibodies might reduce one or more of the CRPS I-like features of the rat fracture model. For our studies one distal tibia of each experimental rat was fractured and casted for 4 weeks. The rats were injected with anti-NGF or vehicle at days 17 and 24 post-fracture. Nociceptive testing as well as assessment of edema and hindpaw warmth were followed during this period. Molecular and biochemical techniques were used to follow cytokine, NGF and neuropeptide levels in hindpaw skin and sciatic nerves. Lumbar spinal cord Fos immunostaining was performed. Bone microarchitecture was measured using microcomputed tomography (mu CT). We found that tibia fracture upregulated NGF expression in hindpaw skin and tibia bone along with sciatic nerve neuropeptide content. We also found nociceptive sensitization, enhanced spinal cord Fos expression, osteopenia and enhanced cytokine content of hindpaw skin on the side of the fracture. Anti-NGF treatment reduced neuropeptide levels in sciatic nerve and reduced nociceptive sensitization. There was less spinal cord Fos expression and bone loss in the anti-NGF treated animals. Conversely, anti-NGF did not decrease hindpaw edema, warmth or cytokine production. Collectively, anti-NGF reduced some but not all signs characteristic of CRPS illustrating the complexity of CRPS pathogenesis and NGF signaling. (c) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available