The effect of thalidomide treatment on vascular pathology and hyperalgesia caused by chronic constriction injury of rat nerve.
Tumor necrosis factor alpha (TNF) may be involved in the pathogenic mechanisms of neuropathic pain by affecting endothelial cells and by upregulation of receptor sensitivity in afferent nerve fibers. To test the hypothesis that TNF plays a role in the vascular changes and the pain-related behavior in an experimental painful neuropathy in rats produced by tying loosely constrictive ligatures around one sciatic nerve, we investigated the effect of thalidomide, a selective blocker of TNF-production in activated macrophages. In rats in which treatment with thalidomide was started preoperatively, there was diminished mechanical allodynia and thermal hyperalgesia during the early stage of the disease. TNF immunohistochemistry revealed reduced endoneurial immunoreactivity on day 5 post surgery as compared to sham-treated animals. The pathologic vascular changes were also reduced in thalidomide-treated rats. Starting treatment with thalidomide at a time point when hyperalgesia was already present did not alter the course of the pain-related behavior. We conclude that preemptive treatment with a substance that blocks production of TNF reduces pain-related symptoms and pathologic vascular changes in the chronic constriction injury model of neuropathic pain.
Sommer
Claudia
C
Department of Neurology, University of Würzburg, Würzburg, Germany Department of Anesthesiology, University of California, San Diego, USA Department of Pathology (Neuropathology), University of California, San Diego, USA Department of Veterans Affairs Medical Center, San Diego, CA, USA.
Marziniak
Martin
M
Myers
Robert R
RR
D000704:Analysis of Variance; D000818:Animals; D002908:Chronic Disease; D003250:Constriction; D004195:Disease Models, Animal; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy*; D007150:Immunohistochemistry; D009437:Neuralgia / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000098:blood supply / Q000293:injuries*; D013792:Thalidomide / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology*; D014652:Vascular Diseases / Q000188:drug therapy*
D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide