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Primary afferents
Presynaptic inhibition “is more powerful than postsynaptic inhibition in
depressing the central excitatory actions of almost all primary
afferent fibres”. (Eccles 1964)
Large
fibers
DA reduces
presynaptic
inhibition of
non-pain
encoding
primary
afferents
X
DA ’s afferent
input to dorsal horn
neurons at stimulus
intensities that
activate nociceptors
minutes
Hernández-Rodríguez, Calvo, Hochman, Quevedo
Garraway & Hochman 2001
DA  inhibits pain and increases non-pain sensory info
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DA release from A11
Electrical stimulation of A11 depresses nociceptive
input to spinal cord dorsal horn neurons
*A11
stim
x
noxious pinch
spontaneous
activity
Fleetwood-Walker et al 1988
brush
DLH
*Substantia nigra (A9) stimulation – no effect
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Isolated spinal cord with hindlimbs in a dish
D2-like agonists block nociceptive
response at the spinal cord level
“A good means to discovery
is to take away certain parts
of a system and to find out
how the rest behaves.”
George Christoph Lichtenberg
(1742-1799)
Is this an important
site of therapeutic
action in RLS?
Hayes & Hochman
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Chronic changes in sensory function could lead to
long-lasting changes in brain structures
 Cortical activity
 Thalamic activity
Peripheral sensitization:
 Spinal cord excitability
Peripheral nerve injury
triggers long-term changes in
excitatory synaptic
transmission in the anterior
cingulate cortex
Xu et al 2008
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Sympathetic preganglionics
Entire CNS sympathetic neural output via spinal cord
Sympathetic neurons
IML
IML
Motoneurons
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DA directly depresses sympathetic output and DA
synthesis has a diurnal rhythm
DA usually hyperpolarizes and
depresses sympathetic activity
DA synthesis in the IML has
a diurnal rhythm
Gladwell and Coote 1999
Coote et al 1981
Clemens, Sawchuk & Hochman 2005
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Sympathetic innervation of muscle and adrenergic
activation of muscle nociceptors
Sympathetic
innervation of muscle
In vitro diaphragm-phrenic nerve preparation
Kniffki et al 1978
Could an increased sympathetic drive
aberrantly activate muscle nociceptors?
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Motor systems
Dopamine activates the spinal cord central
pattern generator for locomotion
Hayes Cheng & Hochman
Kiehn and Kjærulff 1996
Is a facilitated DA drive contributing to PLMS?
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