The impact of free radicals on opioid receptors in tissue injury and inflammation: implications for drug design

Current drug design has largely overlooked that function of G-protein coupled receptors (GPCRs) can differ between healthy and pathological microenvironments. The success of pH-dependent opioid ligands illustrates the therapeutic potential of exploiting such conditions. Redox changes may represent another regulatory component, but functional and <i>in vivo</i> evidence is still lacking. The consideration of microenvironmental factors may enable the development of safer, peripherally acting analgesics and refine GPCR-targeted drug design.