Acute pain resulting from conditions such as headache, muscle spasms, dental problems or following surgery affects 90 million people per year in the US alone. Chronic pain affects a further 40-70 million and is more troubling as it sparks a viscous cycle of clinical problems and often precipitates depression and/or life-style changes. Furthermore, establishing prolonged analgesia free of serious side effects is a particularly challenging area of medicine. The total economic cost of pain is US$100 billion and global sales of analgesics and anti-inflammatories has been estimated as US$18.7 billion worldwide. Analgesia is currently treated by NSAIDs or by opiates. The former is related to well publicized and serious GI problems while the latter causes unwanted side central side effects. Development in both fields has produced strategies to limit both NSAID injury (click here for free access to our recent dossier) and opioid-related side effects. Further clinical options are however still required. Vanilloid receptor ligands represent one promising area. The vanilloids (eg capsaicin and resiniferatoxin) produce pain initially but cause a rapid secondary down-regulation of pain pathways. Since the identification of the vanilloid receptor, VR1, considerably effort has been placed on developing either less pungent agonists or antagonists for this receptor. The latter is particularly appealing but to date few therapeutic candidates have been identified. Thus research recently reported by Spanish researchers who have used a combinatorial approach to identify new, nonpeptidic channel blockers of VR1 is exciting. Using this approach they have developed noncompetitive VR1 antagonists that recognize a receptor site distinct from that of capsaicin. Intraperitoneal administration of antagonists into mice significantly attenuated thermal nociception as measured in the hot plate test. It is noteworthy that these compounds also eliminated pain and neurogenic inflammation evoked by intradermal injection of capsaicin into the animal hindpaw, as well as the thermal hyperalgesia induced by tissue irritation with nitrogen mustard. The further development of this series thus holds significant promise for the field of analgesia.

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