Intrathecal noradrenaline restores 5-methoxy-N,N-dimethyltryptamine induced antinociception abolished by intrathecal 6-hydroxydopamine.
Journal of neural transmission – January 01, 1988
Source: PubMed
Summary
A striking 95% depletion of noradrenaline in spinal regions eliminated the pain-relieving effects of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) across various pain tests. However, restoring noradrenaline prior to 5-MeODMT reinstated its analgesic effects. Additionally, severe serotonin depletion from intrathecal administration further diminished 5-MeODMT's effectiveness. This underscores the critical role of noradrenaline in enhancing serotonin's ability to alleviate pain, highlighting how neurotransmitter availability can significantly influence pain management strategies.
Abstract
Intrathecal administration of 6-hydroxydopamine (6-OHDA) abolished the antinociceptive effects of acute administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 1 mg/kg, s.c.) in the hot-plate, tail-flick and shock titration tests of nociception. The antinociceptive effects of 5-MeODMT, abolished by the prior intrathecal 6-OHDA treatment, were restored by intrathecal administration (2 or 1 microgram) of noradrenaline (NA), immediately prior to 5-MeODMT, in all three tests of nociception. Biochemical analysis confirmed severe NA depletions (95 percent loss) in the lumbar and thoracic regions of the spinal and much lesser dopamine depletions (25-35 percent loss). Intrathecal 5,7-dihydroxytryptamine (5,7-DHT) attenuated 5-MeODMT induced antinociception in the tail-flick test and combined NA + 5-MeODMT induced antinociception in the hot-plate and tail-flick tests. Intrathecal administration of 5,7-DHT caused a severe depletion of 5-hydroxytryptamine in the lumbar region of the spinal cord. The present findings demonstrate further the modulatory role of NA upon serotonergic systems in nociception and indicate the necessity of NA availability for induction of 5-MeODMT analgesia.