The primary objective of this trial is to determine the effect on pain intensity scored of ZD6416 1600 mg administered twice daily for 2 weeks in adult subjects with painful distal symmetrical sensory polyneuropathy (DSSP) compared with placebo. Of the 5 known prostanoid mediators that are synthesized in man, prostaglandin E2 (PGE2) appears to play an important role in the modulation of pain in the periphery (Egg 1984) and in the spinal cord (Coderre et al 1990). There is evidence that PGE2 can interact with at least 4 distinct receptors EP1, EP2, EP3 and EP4 (Coleman et al 1994). The modulation of pain responses by PGE2 appears to be due to its actions at the EP1 receptor because of putative EP1 receptor antagonist AH6809 was shown to antagonize the hyperalgesic effects of intrathecally applied PGE2 in animals (Uda et al 1990). In animal models of pain (Bennett 1994), which are thought to involve central sensitization (second phase formalin model and chronic constriction injury model), EP1 antagonists developed by Zeneca Pharmaceuticals, Zeneca Inc. (Zeneca), and including ZD6416, have been shown to be analgesic. This trial, which is designed to assess whether ZD6416 is analgesic in subjects with neuropathic pain secondry to diabetic distal symmetrical sensory polyneuropathy (DSSP), as the pain in this condition is thought to involve pain mechanisms including central sensitization.
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