Role of nucleus accumbens in neuropathic pain: Linked multi-scale evidence in the rat transitioning to neuropathic pain

Pei Ching Chang, Sarah Lynn Pollema-Mays, Maria Virginia Centeno, Daniel Procissi, Massimo Contini, Alex Tomas Baria, Marco Martina, Apkar Vania Apkarian*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

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 languageEnglish (US)
Pages (from-to)1128-1139
Number of pages12
JournalPain
Volume155
Issue number6
DOIs
StatePublished - Jun 2014

Funding

We are grateful to Drs. M. Baliki and A. Mansour for suggestions regarding the rat fMRI data analysis, and also to all other members of the Apkarian lab for reading and commenting on the manuscript, and especially Dr. M. Farmer for editing the manuscript. This work was supported by the National Institute of Health grants NS057704 and DE022746 (A.V.A.), and NS064091 (M.M.).

Keywords

  • Addiction
  • Allodynia
  • Dopamine
  • Opioid
  • Resting state
  • fMRI

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Anesthesiology and Pain Medicine

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