Time-dependent changes in the activity of opioid systems in the spinal cord of monoarthritic rats--a release and in situ hybridization study

Neuroscience. 1992;46(1):209-16. doi: 10.1016/0306-4522(92)90020-3.


The activity of the endogenous opioid systems was analysed in the spinal cord of rats 12 h, one, five or 14 days after injection of the Freund Adjuvant into the hind limb sole. The tissue level of immunoreactive Met-enkephalin-Arg6-Gly7-Leu8, a peptide derived from proenkephalin, started to rise 12 h after Freund Adjuvant inoculation and remained enhanced until day 14. The spontaneous release of the immunoreactive Met-enkephalin-Arg6-Gly7-Leu8 was also elevated at all the examined time points, the peak occurring on day 1. No changes were observed in the stimulated release except on day 14, when the peptide release was decreased. The proenkephalin messenger RNA level was enhanced at all the time points on the ipsilateral side of the spinal cord in laminae I-II, whereas in lamina V an increase was observed only on days 1 and 5. An increase in the proenkephalin messenger RNA level on the contralateral side was observed only in laminae I-II and only on days 1 and 5. The tissue level of immunoreactive alpha-neoendorphin, a peptide derived from prodynorphin, was significantly increased on days 5 and 14. The spontaneous immunoreactive alpha-neoendorphin release from spinal cord slices was elevated at all the time points studied, whereas the stimulated release of the peptide was strongly increased 12 h after Freund Adjuvant inoculation but gradually declined on the following days. An in situ hybridization study showed that the prodynorphin messenger RNA level in laminae I-II was increased at all the examined time points.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / physiopathology*
  • Endorphins / physiology*
  • Enkephalin, Methionine / metabolism
  • Enkephalins / biosynthesis
  • In Vitro Techniques
  • Male
  • Nucleic Acid Hybridization
  • Oligonucleotide Probes
  • Protein Precursors / biosynthesis
  • RNA, Messenger / metabolism
  • Radioimmunoassay
  • Rats
  • Rats, Inbred Strains
  • Spinal Cord / metabolism
  • Spinal Cord / physiopathology*
  • Sulfur Radioisotopes


  • Endorphins
  • Enkephalins
  • Oligonucleotide Probes
  • Protein Precursors
  • RNA, Messenger
  • Sulfur Radioisotopes
  • proenkephalin
  • Enkephalin, Methionine
  • preproenkephalin