Nothing has arguably hurt pharmaceutical investors and dealmakers quite so often and with such force as novel pain drug development failures. As a result, a once hot field has gone cold. Despite setbacks, great strides have been made in understanding the complex biology of pain. Scientists have discovered numerous new pain pathway targets with the potential for designing effective agents with fewer off-target effects. Improvements that make preclinical studies more predictive of clinical success are also opening up new opportunities. At the same time, drug developers now understand better how to design drug trials that can segment patient populations to demonstrate therapeutic efficacy more precisely, potentially reducing placebo effects and paving the way for an era of personalized pain medicine.

Mark Greener reviews a selection of ion channels currently attracting researchers' attention, demonstrating renewed interest in the clinical and commercial potential of an underexploited therapeutic target

Given the paucity of novel pain drugs and the calamities surrounding Vioxx and OxyContin, Big Pharma has a keen interest in finding alternatives. Working within the G-protein coupled receptor superfamily, Cara Therapeutics hopes to oblige.

A preview of the emerging health care companies profiled in the current issue of Start-Up. This month's profile groups: GI Drug Development: AGI Therapeutics, Napo Pharmaceuticals, Tioga Pharmaceuticals. Plus these Start-Ups across Health Care: Cierra, PainCeptor, Tengion, TyRx Pharma.