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The Journal of Neuroscience, December 15, 2002, 22(24):10847-10855
Rostral Ventromedial Medulla Neurons That Project to the Spinal
Cord Express Multiple Opioid Receptor Phenotypes
Silvia
Marinelli1,
Christopher W.
Vaughan1, 2,
Stephen A.
Schnell3,
Martin
W.
Wessendorf3, and
MacDonald J.
Christie1
1 Department of Pharmacology and The Medical
Foundation, The University of Sydney, Sydney, New South Wales
2006 Australia, 2 Department of Anaesthesia and Pain
Management, Royal North Shore Hospital New South Wales, New South Wales
2065 Australia, and 3 Department of Neuroscience,
University of Minnesota, Minneapolis, Minnesota 55455
The rostral ventromedial medulla (RVM) forms part of a descending
pathway that modulates nociceptive neurotransmission at the level of
the spinal cord dorsal horn. However, the involvement of descending RVM
systems in opioid analgesia are a matter of some debate. In the present
study, patch-clamp recordings of RVM neurons were made from rats that
had received retrograde tracer injections into the spinal cord. More
than 90% of identified spinally projecting RVM neurons responded to
opioid agonists. Of these neurons, 53% responded only to the
µ-opioid agonist D-Ala2, N-Me-Phe4, Gly-ol5 enkephalin, 14% responded only to the  -opioid
agonist U-69593, and another group responded to both µ and opioids (23%). In unidentified RVM neurons, a larger proportion
of neurons responded only to µ opioids (75%), with smaller
proportions of - (4%) and µ/-opioid (13%) responders. These
RVM slices were then immunostained for tryptophan hydroxylase (TPH), a
marker of serotonergic neurons. Forty-percent of spinally projecting
neurons and 11% of unidentified neurons were TPH positive. Of the
TPH-positive spinally projecting neurons, there were similar
proportions of µ- (33%), - (25%), and µ/-opioid (33%)
responders. Most of the TPH-negative spinally projecting neurons were
µ-opioid responders (67%). These findings indicate that functional
opioid receptor subtypes exist on spinally projecting serotonergic and
nonserotonergic RVM neurons. The proportions of µ- and -opioid
receptors expressed differ between serotonergic and nonserotonergic
neurons and between retrogradely labeled and unlabeled RVM neurons. We
conclude that important roles exist for both serotonergic and
nonserotonergic RVM neurons in the mediation of opioid effects.
Key words:
rostral ventromedial medulla; spinal cord; opioid
receptor; analgesia; serotonergic; patch clamp; immunohistochemistry
Copyright © 2002 Society for Neuroscience 0270-6474/02/222410847-09$05.00/0
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