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
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.