Spinal actions of nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the signs and symptoms of inflammation. They originated from man's early use of willow bark in the treatment of rheumatism. Although these drugs have been developed because of their effects on arthritis, their substantial analgesic and antipyretic actions have led to their widespread application. The NSAIDs are classified on the basis of their chemical structure under the category of acidic and nonacidic agents. The anti-inflammatory, analgesic and antipyretic effects of NSAIDs are attributable to their suppression of prostaglandin synthesis activity through cyclooxygenase inhibition. Regarding the analgesic effects of NSAIDs, initially, the peripheral mechanism was proposed. It has been assumed that the effects result from inhibition of the synthesis of prostaglandins in the peripheral inflamed tissue because prostaglandin may sensitize the peripheral nociceptors to the effects of other mediators released from the inflamed tissue. However, the central mechanism, acting within supraspinal or spinal level, was also suggested recently. Their exact sites and modes of action within the spinal cord are poorly defined, and even controversial. There are two main hypotheses to elucidate this issue. One is that the spinal analgesic actions are associated with prostaglandins synthesis, because of the excitatory effect of prostaglandins in the spinal cord and the other is dissociated from prostaglandins synthesis, and their effect may be related to their ability to affect the spinal nociceptive, processing cellularly or intracellularly. However, both mechanisms are probably linked. In conclusion, although the real mechanisms of the spinal analgesic actions of NSAIDs remain unclear, further basic and clinical studies should be made. In this way, we may hopefully provide more opportunities for effective pain management.