Highlights
- •Neuropathic pain resulted in loss dopamine and rise in norepinephrine content in the ventral striatum.
- •Pain thresholds no longer correlated with ventral striatal dopamine content in neuropathic pain.
- •Ventral striatal norepinephrine content correlated with pain thresholds only in neuropathic pain.
- •These results point to a dramatic change in striatal catecholamine signaling in neuropathic pain.
Abstract
Neuropathic pain is characterized by persistent, intractable pain following damage
or dysfunction of the nervous system. Analgesics that include central, rather than
purely peripheral, targets are more effective when treating neuropathic pain, highlighting
the spinal and/or supraspinal mechanisms that contribute to this aberrant pain condition.
The striatum represents one of the brain regions that have been implicated in pain
processing. Release of dopamine in the ventral striatum is normally associated with
analgesia. Clinical and human imaging studies suggest that dopamine is disrupted in
neuropathic pain patients, although the conclusions drawn from these studies are limited
by their noninvasive imaging or pharmacologic approaches. In this study, we used a
C57Bl/6 mouse model of neuropathic pain to describe the changes in neurotransmitter
content in the striatum and their relationship to evoked pain thresholds. Striatal
dopamine content negatively correlated with mechanical thresholds in sham animals.
Neuropathic pain animals had reduced dopamine content that was not correlated with
mechanical thresholds. In contrast, norepinephrine content was significantly increased
and correlated with mechanical thresholds in neuropathic, but not sham, animals. These
results describe changes in striatal signaling in neuropathic pain animals and contribute
to the literature defining the role of dopamine and norepinephrine in mediating sensory
thresholds in healthy and neuropathic pain states.
Perspective
Results show significant loss of ventral striatal dopamine in neuropathic pain conditions,
and the relationship of ventral striatal catecholamines to pain thresholds is changed
in neuropathic pain. These results complement human imaging studies and provide evidence
that chronic pain alters the function of reward systems.
Key words
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Article info
Publication history
Published online: June 02, 2014
Accepted:
May 27,
2014
Received in revised form:
May 20,
2014
Received:
April 4,
2014
Footnotes
This study was supported by the National Institutes of Health (DA005010) (C.J.E.), Canadian Institutes of Health Research (MOP 123298) (C.M.C. and A.M.W.T.), and the Shirley and Stefan Hatos Foundation (C.J.E., N.P.M., and A.M.W.T.).
The authors declare no conflict of interest.
Identification
Copyright
© 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.
