Endogenous opioid immunoreactivity in rat spinal cord following traumatic injury.
It has been postulated that endogenous opioids play a pathophysiological role in spinal cord injury, based on the therapeutic effects of the opiate receptor antagonist naloxone in certain experimental models. The high doses of naloxone required to exert a therapeutic action suggest that naloxone's effects may be mediated by non-mu opiate receptors, such as the kappa receptor. This notion is supported by recent pharmacological studies demonstrating that an opiate antagonist more active at kappa sites is effective and far more potent than naloxone in improving outcome after spinal cord injury. Moreover, dynorphin--postulated to be the endogenous ligand for the kappa receptor--is unique among opioids in producing hindlimb paralysis following intrathecal administration in the rat. In the present studies we have examined changes in endogenous opioid immunoreactivity following traumatic spinal cord injury in the rat. Dynorphin A was found to increase progressively with graded injury; changes were restricted to the injury segment and adjacent areas and were time dependent. Dynorphin A-(1-8) showed no marked changes. Methionine and leucine enkephalin were either unaltered or reduced at the injury site; changes were not well localized and were not clearly related to the injury variables. These findings provide further support for a potential pathophysiological role of prodynorphin-derived peptides in spinal cord injury.
Faden
A I
AI
Molineaux
C J
CJ
Rosenberger
J G
JG
Jacobs
T P
TP
Cox
B M
BM
D000818:Animals; D004399:Dynorphins / Q000032:analysis; D004723:Endorphins / Q000032:analysis*; D004744:Enkephalin, Methionine / Q000032:analysis; D007930:Leucine / Q000032:analysis; D010446:Peptide Fragments / Q000032:analysis; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism*; D013997:Time Factors
D004723:Endorphins; D010446:Peptide Fragments; D004744:Enkephalin, Methionine; D004399:Dynorphins; C040238:dynorphin A (1-9); D007930:Leucine