Cyclooxygenase-2 in the spinal cord: localization and regulation after a peripheral inflammatory stimulus.


Prostaglandins are known as mediators in spinal nociceptive processing after peripheral inflammation. Cyclooxygenase isozymes Cox-1 and Cox-2 as enzymes essential for prostaglandin biosynthesis were therefore investigated in rat spinal cord. mRNA and protein of both enzymes was detected in cervical and lumbar sections of the spinal cord of normal animals. Enzyme activity of Cox-1 and Cox-2 could be determined by the use of specific inhibitors. Cox-2-immunoreactivity (IR) was found in the spinal cord of untreated rats in neurons of laminae II-III, motoneurons of lamina IX and in glial cells. Most prominent staining was observed in the nuclear envelope. Under an acute peripheral inflammatory stimulus a transient 2-fold increase in Cox-2 mRNA was noticed bilaterally in the lumbar spinal cord by reverse transcription-polymerase chain reaction. This increase was reflected on a smaller scale at protein levels in Western blot analysis of spinal membrane preparations. In the chronic state of adjuvant-induced arthritis, Cox-2 levels were raised again significantly. Cox-2 might therefore be regarded as the Cox isozyme responsible for increased spinal prostanoid release in nociceptive processing under peripheral stimulation.


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