Abstract
The effectiveness of epidural analgesics is well known. Among drugs used for epidural analgesia, morphine, a μ agonist, is most popular. However, μ agonists have a variety of side effects. κ agonists have fewer side effects than μ agonists, and many κ receptors are expressed in the spinal cord. Therefore, epidural κ agonists are appropriate for epidural administration. For analgesia of the face and head innervated by the trigeminal nerve, the effectiveness of cervical epidural κ opioids is evident because the spinal trigeminal nucleus extends into the spinal cord to C1 and C2. On the other hand, epidural NMDA antagonists do not block AMPA receptors that transmit primary afferent nociception. Therefore, epidural NMDA antagonists are inappropriate for epidural analgesia. NMDA antagonists suppress pain-facilitating mechanisms, such as central sensitization, windup, and long-term potentiation, have synergism with opioids, and inhibit opioid tolerance and addiction. Thus, epidural NMDA antagonists may be useful in treatment of chronic spinal pain, and as a supplement for opioids. However, the effect is different from analgesia, and systemic administration of NMDA antagonists may be more beneficial because NMDA antagonists appear to act more effectively for supraspinal mechanisms. About ketamine, the specificity is low, thus ketamine may have various effects, including analgesia (with a lower dose) and anesthesia (with a higher dose) .
