INTERVENTION WITH SPINAL NMDA, ADENOSINE, AND NO SYSTEMS FOR PAIN MODULATION

Understanding of the complex pharmacology of the spinal cord may lead to rational advances in pain treatment It appears that a number of spe cific neurochemical mechanisms exist, by which spinally administered r eceptor selective agents may modify nociceptive transmission. Spinal a dministration of pure competitive N-methyl-D-aspartate (NMDA) antagoni sts affects only hyperpathic pain components, i.e. with signs of centr al sensitization, and most probably has a very limited role in postope rative pain treatment. On the other hand, it is well established that the non-competitive NMDA-antagonist ketamine gives good postoperative analgesia, probably by cerebral mechanisms also affecting other sensor y modalities. Pure adenosine A(1)-receptor agonism at the spinal level mainly affects sensory allodynia to vibration, and is probably no alt ernative for postoperative pain treatment. In contrast, i.v. infusions of the non-selective A(1)/A(2)-receptor agonist adenosine given durin g a surgical procedure seem to decrease postoperative pain and require ments for postoperative analgesia. This apparent contradiction must be analysed further. Several drugs commonly used to treat postoperative pain, such as opioids, NSAIDs, ketamine and paracetamol, are linked to nitric oxide (NO) in their mechanism of action. The biosynthesis of N O in the central nervous system (CNS) is tonically involved in the noc iceptive processing.