Breaking barriers to novel analgesic drug development

Abstract

Existing pain therapies are often inadequate or associated with side effects. Here, Woolf and colleagues discuss new and existing strategies for the development of improved pain therapeutics, highlighting key challenges and considerations in the clinical development of novel analgesics. Acute and chronic pain complaints, although common, are generally poorly served by existing therapies. This unmet clinical need reflects a failure to develop novel classes of analgesics with superior efficacy, diminished adverse effects and a lower abuse liability than those currently available. Reasons for this include the heterogeneity of clinical pain conditions, the complexity and diversity of underlying pathophysiological mechanisms, and the unreliability of some preclinical pain models. However, recent advances in our understanding of the neurobiology of pain are beginning to offer opportunities for developing novel therapeutic strategies and revisiting existing targets, including modulating ion channels, enzymes and G-protein-coupled receptors.