The peripheral analgesic effects of opioids

Results from numerous studies indicate that opioids produce effects through activation of receptors located in the central nervous system at spinal and supraspinal levels. However, opioids may also possess peripheral analgesic activity. Behavioral studies conducted in animals indicate that mu, kappa, and delta selective opioids possess significant antinociceptive activity after injection into hyperalgesic tissue by activation of a peripheral mechanism(s). These effects appear to be predominantly receptor- selective since they are dose-related, stereospecific, and blocked by administration of receptor antagonists. Recent clinical trials suggest that opioids activate a peripherally mediated analgesic mechanism in clinical models of pain due to inflammation. These results suggest that peripherally administered opioids or development of peripherally selective opioids may provide clinical analgesia without the development of traditional central nervous system mediated side effects.