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 and opioid-related side effects. Further clinical options are however still required and the entire future of pain therapeutics continues to be a major priorty of the pharmaceutical industry (click here for "Pain 2002" an analysis of future directions in analgesic therapeutics). 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, considerable effort has been placed on developing either less pungent agonists or antagonists for this receptor. A second emmerging field focuses on neural ion channels. In this respect research emerging from Yale University School of Medicine is particularly interesting. The Na(v)1.9 Na(+) channel (also known as NaN) is preferentially expressed in nociceptive neurons of the dorsal root ganglia (DRG) and trigeminal ganglia. Na(v)1.9 produces a persistent, tetrodotoxin-resistant current and appears to modulate resting potential and to amplify small depolarizations. These unique properties indicate that Na(v)1.9 has significant effects on the electroresponsive properties of primary nociceptive neurons. Peripheral axotomy, which is a model of neuropathic pain, downregulates Na(v)1.9 which has been proposed to contribute to the hyperexcitability of DRG neurons after nerve injury. Thus, Na(v)1.9 appears to represent a selective and effective target for novel analgesics.

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