Opioids for the treatment of arthritis pain.

INTRODUCTION: Centrally acting opioids are well established in the treatment of acute, surgical and cancer pain. However, their use in chronic noncancer pain (CNCP) is controversial because of side effects such as tolerance, somnolence, respiratory depression, confusion, constipation and addiction. Chronic arthritis and other musculoskeletal diseases are among the leading causes of CNCP. AREAS COVERED: This manuscript will discuss the role of conventional opioids in chronic arthritis. In addition, future developments and strategies exploiting peripheral effects of opioids on pain and inflammation will be outlined. EXPERT OPINION: Aims in drug development include the design of peripherally restricted opioid agonists, selective targeting of endogenous opioids to sites of painful injury and the augmentation of peripheral ligand and receptor synthesis, for example, by gene therapy. Although a large number of peripherally acting opioid compounds have been developed, clinical Phase III studies have not been published so far. Another strategy is to augment the effects of endogenously released opioid peptides by the inhibition of their degrading enzymes. Technology-oriented research is needed to find novel ways of peripheral restriction of opioids. Such analgesics would be desirable for their lack of central side effects and of adverse effects typical of nonsteroidal anti-inflammatory drugs (gastrointestinal ulcers, bleeding, myocardial infarction and stroke).