Trial Information

Evaluation of TNF-Alpha Modulator for Clinical and Molecular Indicators of Analgesic Effect

The proposed investigation is a randomized, double-blind, placebo and positive-controlled
clinical study to evaluate the role of the cytokine tumor necrosis factor alpha (TNF-alpha)
modulator, thalidomide, in acute inflammation and analgesia. The analgesic effect of
thalidomide, a putative TNF-alpha modulator, will be evaluated using a model of tissue
injury, the oral surgery model. Briefly, healthy males referred for third molar extraction
will undergo the surgical extraction of third molars using standard surgical methods. At the
completion of the surgical procedure, a microdialysis probe will be placed under the
mucogingival flap previously elevated for the surgical procedure and subjects will be
observed for pain over the course of six hours following surgery. Thalidomide or control
will be administered one hour prior to surgery. Tissue levels of pro-inflammatory
cytokines, and inflammatory mediators will be measured at time intervals postoperatively
concomitant with pain measurements. Pain will be assessed postoperatively over the course
of six hours. Demonstration of amelioration of pain is the primary outcome measure; changes
in levels of tissue mediators will be taken as evidence of an acute anti-inflammatory effect
of thalidomide. Based on our previous work with the fusion protein etanercept (TNFR:fc)
which specifically binds TNF-alpha and prevents its interaction with cellular receptors,
similar changes in the inflammatory cascade and clinical endpoints of inflammation may
provide insight into the activity of thalidomide on acute inflammation and its clinical
sequela, pain.