EFFECTS OF KELATORPHAN AND MORPHINE BEFORE AND AFTER NOXIOUS-STIMULATION ON IMMEDIATE-EARLY GENE-EXPRESSION IN RAT SPINAL-CORD NEURONS

Citation
Tr. Tolle et al., EFFECTS OF KELATORPHAN AND MORPHINE BEFORE AND AFTER NOXIOUS-STIMULATION ON IMMEDIATE-EARLY GENE-EXPRESSION IN RAT SPINAL-CORD NEURONS, Pain, 56(1), 1994, pp. 103-112
Citations number
77
Categorie Soggetti
Neurosciences
Journal title
PainACNP
ISSN journal
03043959
Volume
56
Issue
1
Year of publication
1994
Pages
103 - 112
Database
ISI
SICI code
0304-3959(1994)56:1<103:EOKAMB>2.0.ZU;2-W
Abstract
Expression of the immediate-early genes (IEG) c-FOS, NGF1-A and c-JUN was induced by noxious thermal stimulation in neurons of the rat spina l cord dorsal horn. Intravenous injection of Kelatorphan (5, 10 and 20 mg/kg), an inhibitor of multiple enkephalin-degrading enzymes, 20 min before noxious stimulation reduced the overall number of dorsal horn neurons expressing c-FOS and NGF1-A by up to 20-30%. While c-FOS expre ssion was suppressed in superficial and deep laminae of the spinal cor d, NGF1-A and c-JUN was only suppressed in superficial laminae. Morphi ne (5, 7.5 and 10 mg/kg) produced a dose-dependent reduction of c-FOS expression by up to 70% only when injected before noxious stimulation. Morphine injected 10 min after the noxious treatment was virtually in effective. The depressant effect of Kelatorphan and morphine could be prevented by prior application of the opioid antagonist naloxone. Nalo xone itself slightly increased the overall number of c-FOS-positive ne urons in all laminae of the spinal cord. The present data support the existence of a tonic release of endogenous opioid peptides at the spin al level and show that inhibition of their peptidase-induced degradati on modulates IEG expression in dorsal horn neurons of the rat. The fin ding that opioid agonists were ineffective when applied after stimulat ion underline the necessity of pre-emptive analgesia to prevent long-t erm activity-dependent changes in spinal cord neurons.