title: Role of nucleus accumbens in neuropathic pain: linked multi-scale evidence in the rat transitioning to neuropathic pain.
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 28days (but not 5days) after SNI; (2) Contralateral to SNI injury, gene expression of NAc dopamine 1A, 2, and κ-opioid receptors decreased 28days after SNI; (3) In SNI (but not sham), covariance of gene expression was upregulated at 5days and settled to a new state at 28days; 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.
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA Dipartimento di Medicina Sperimentale e Clinica, sez. Fisiologia, Università di Firenze, I-50134 Firenze, Italy.
authors.forename: Pei-Ching
authors.initials: PC
authors.lastname: Chang
authors.forename: Sarah Lynn
authors.initials: SL
authors.lastname: Pollema-Mays
authors.forename: Maria Virginia
authors.initials: MV
authors.lastname: Centeno
authors.forename: Daniel
authors.initials: D
authors.lastname: Procissi
authors.forename: Massimo
authors.initials: M
authors.lastname: Contini
authors.forename: Alex Tomas
authors.initials: AT
authors.lastname: Baria
authors.forename: Marco
authors.initials: M
authors.lastname: Martina
authors.forename: Apkar Vania
authors.initials: AV
authors.lastname: Apkarian
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D009437:Neuralgia / Q000473:pathology* / Q000503:physiopathology*; D009714:Nucleus Accumbens / Q000502:physiology*; D010147:Pain Measurement / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Addiction; Allodynia; Dopamine; Opioid; Resting state; fMRI