Abstract
Despite recent evidence implicating the nucleus accumbens (NAc) as causally involved in the transition to chronic pain in humans, underlying mechanisms of this involvement remain entirely unknown. Here we elucidate mechanisms of NAc reorganizational properties (longitudinally and cross-sectionally), in an animal model of neuropathic pain (spared nerve injury [SNI]). We observed interrelated changes: (1) In resting-state functional magnetic resonance imaging (fMRI), functional connectivity of the NAc to dorsal striatum and cortex was reduced 28 days (but not 5 days) after SNI; (2) Contralateral to SNI injury, gene expression of NAc dopamine 1A, 2, and κ-opioid receptors decreased 28 days after SNI; (3) In SNI (but not sham), covariance of gene expression was upregulated at 5 days and settled to a new state at 28 days; and (4) NAc functional connectivity correlated with dopamine receptor gene expression and with tactile allodynia. Moreover, interruption of NAc activity (via lidocaine infusion) reversibly alleviated neuropathic pain in SNI animals. Together, these results demonstrate macroscopic (fMRI) and molecular reorganization of NAc and indicate that NAc neuronal activity is necessary for full expression of neuropathic pain-like behavior.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1128-1139 |
| Number of pages | 12 |
| Journal | Pain |
| Volume | 155 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jan 1 2014 |
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Keywords
- Addiction
- Allodynia
- Dopamine
- Opioid
- Resting state
- fMRI
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
- Anesthesiology and Pain Medicine
Cite this
}
Role of nucleus accumbens in neuropathic pain : Linked multi-scale evidence in the rat transitioning to neuropathic pain. / Chang, Pei Ching; Pollema-Mays, Sarah Lynn; Centeno, Maria Virginia; Procissi, Daniele; Contini, Massimo; Baria, Alex Tomas; Martina, Marco; Apkarian, Apkar.
In: Pain, Vol. 155, No. 6, 01.01.2014, p. 1128-1139.Research output: Contribution to journal › Article
TY - JOUR
T1 - Role of nucleus accumbens in neuropathic pain
T2 - Linked multi-scale evidence in the rat transitioning to neuropathic pain
AU - Chang, Pei Ching
AU - Pollema-Mays, Sarah Lynn
AU - Centeno, Maria Virginia
AU - Procissi, Daniele
AU - Contini, Massimo
AU - Baria, Alex Tomas
AU - Martina, Marco
AU - Apkarian, Apkar
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Despite recent evidence implicating the nucleus accumbens (NAc) as causally involved in the transition to chronic pain in humans, underlying mechanisms of this involvement remain entirely unknown. Here we elucidate mechanisms of NAc reorganizational properties (longitudinally and cross-sectionally), in an animal model of neuropathic pain (spared nerve injury [SNI]). We observed interrelated changes: (1) In resting-state functional magnetic resonance imaging (fMRI), functional connectivity of the NAc to dorsal striatum and cortex was reduced 28 days (but not 5 days) after SNI; (2) Contralateral to SNI injury, gene expression of NAc dopamine 1A, 2, and κ-opioid receptors decreased 28 days after SNI; (3) In SNI (but not sham), covariance of gene expression was upregulated at 5 days and settled to a new state at 28 days; and (4) NAc functional connectivity correlated with dopamine receptor gene expression and with tactile allodynia. Moreover, interruption of NAc activity (via lidocaine infusion) reversibly alleviated neuropathic pain in SNI animals. Together, these results demonstrate macroscopic (fMRI) and molecular reorganization of NAc and indicate that NAc neuronal activity is necessary for full expression of neuropathic pain-like behavior.
AB - Despite recent evidence implicating the nucleus accumbens (NAc) as causally involved in the transition to chronic pain in humans, underlying mechanisms of this involvement remain entirely unknown. Here we elucidate mechanisms of NAc reorganizational properties (longitudinally and cross-sectionally), in an animal model of neuropathic pain (spared nerve injury [SNI]). We observed interrelated changes: (1) In resting-state functional magnetic resonance imaging (fMRI), functional connectivity of the NAc to dorsal striatum and cortex was reduced 28 days (but not 5 days) after SNI; (2) Contralateral to SNI injury, gene expression of NAc dopamine 1A, 2, and κ-opioid receptors decreased 28 days after SNI; (3) In SNI (but not sham), covariance of gene expression was upregulated at 5 days and settled to a new state at 28 days; and (4) NAc functional connectivity correlated with dopamine receptor gene expression and with tactile allodynia. Moreover, interruption of NAc activity (via lidocaine infusion) reversibly alleviated neuropathic pain in SNI animals. Together, these results demonstrate macroscopic (fMRI) and molecular reorganization of NAc and indicate that NAc neuronal activity is necessary for full expression of neuropathic pain-like behavior.
KW - Addiction
KW - Allodynia
KW - Dopamine
KW - Opioid
KW - Resting state
KW - fMRI
UR - http://www.scopus.com/inward/record.url?scp=84899896161&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899896161&partnerID=8YFLogxK
U2 - 10.1016/j.pain.2014.02.019
DO - 10.1016/j.pain.2014.02.019
M3 - Article
C2 - 24607959
AN - SCOPUS:84899896161
VL - 155
SP - 1128
EP - 1139
JO - Pain
JF - Pain
SN - 0304-3959
IS - 6
ER -