Opioid systems modulate nociceptive input at several levels of the CNS. At the spinal cord level neurons are present that express the genes coding for the precursors of the
dynorphin and
enkephalin opioid peptide families. We found that two conditions in rats, a chronic constriction injury to the sciatic nerve and peripheral
inflammation, have a common consequence centrally: they evoke a large, rapid and sustained up-regulation of
preprodynorphin mRNA. Both are also characterized by signs of
hyperalgesia and increased primary afferent input. In contrast, there is little or no up-regulation of
preprodynorphin mRNA following complete transection of the sciatic nerve or sciatic nerve crush. Furthermore, only minor alterations in the levels of
preproenkephalin mRNA occur in any of the conditions, except for
inflammation where the elevation is relatively small compared to that of
preprodynorphin mRNA. These data imply that specific regulatory processes that include stimulation of
opioid gene expression are strongly engaged in the spinal cord in certain types of
peripheral nerve injuries and
inflammation, but not in others. Marked and sustained up-regulation of the spinal cord
dynorphin system distinguishes the chronic constriction injury model from other nerve injury models of
pain.