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.