title: Persistent pain alters AMPA receptor subunit levels in the nucleus accumbens.
abstract: BACKGROUND
  A variety of pain conditions have been found to be associated with depressed mood in clinical studies. Depression-like behaviors have also been described in animal models of persistent or chronic pain. In rodent chronic neuropathic pain models, elevated levels of GluA1 subunits of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the nucleus accumbens (NAc) have been found to inhibit depressive symptoms. However, the effect of reversible post-surgical pain or inflammatory pain on affective behaviors such as depression has not been well characterized in animal models. Neither is it known what time frame is required to elicit AMPA receptor subunit changes in the NAc in various pain conditions.
  
  
  RESULTS
  In this study, we compared behavioral and biochemical changes in three pain models: the paw incision (PI) model for post-incisional pain, the Complete Freund's Adjuvant (CFA) model for persistent but reversible inflammatory pain, and the spared nerve injury (SNI) model for chronic postoperative neuropathic pain. In all three models, rats developed depressive symptoms that were concurrent with the presentation of sensory allodynia. GluA1 levels at the synapses of the NAc, however, differed in these three models. The level of GluA1 subunits of AMPA-type receptors at NAc synapses was not altered in the PI model. GluA1 levels were elevated in the CFA model after a period (7 d) of persistent pain, leading to the formation of GluA2-lacking AMPA receptors. As pain symptoms began to resolve, however, GluA1 levels returned to baseline. Meanwhile, in the SNI model, in which pain persisted beyond 14 days, GluA1 levels began to rise after pain became persistent and remained elevated. In addition, we found that blocking GluA2-lacking AMPA receptors in the NAc further decreased the depressive symptoms only in persistent pain models.
  
  
  CONCLUSIONS
  Our study shows that while both short-term and persistent pain can trigger depression-like behaviors, GluA1 upregulation in the NAc likely represents a unique adaptive response to minimize depressive symptoms in persistent pain states.
authors.affiliation: Department of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. su.chen@nyumc.org.
authors.forename: Chen
authors.initials: C
authors.lastname: Su
authors.affiliation: Departments of Otolaryngology and Physiology and Neuroscience, The Helen and Martin Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, NY, USA. James.D'Amour@med.nyu.edu.
authors.forename: James
authors.initials: J
authors.lastname: D'amour
authors.affiliation: Department of Anesthesiology, New York University School of Medicine, New York, NY, USA. michelle.lee022@gmail.com.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology, New York University School of Medicine, New York, NY, USA. hauyuehlin@gmail.com.
authors.forename: Hau-Yeuh
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, New York University School of Medicine, New York, NY, USA. trm2124@gmail.com.
authors.forename: Toby
authors.initials: T
authors.lastname: Manders
authors.affiliation: Department of Anesthesiology, New York University School of Medicine, New York, NY, USA. Duo.Xu@med.nyu.edu.
authors.forename: Duo
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, New York University School of Medicine, New York, NY, USA. sarah.e.eberle@gmail.com.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Eberle
authors.affiliation: Department of Anesthesiology, New York University School of Medicine, New York, NY, USA. yg2149@gmail.com.
authors.forename: Yossef
authors.initials: Y
authors.lastname: Goffer
authors.affiliation: Department of Anesthesiology, New York University School of Medicine, New York, NY, USA. tonyhzou@gmail.com.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Zou
authors.affiliation: Columbia College, New York, NY, USA. maishyx16@gmail.com.
authors.forename: Maisha
authors.initials: M
authors.lastname: Rahman
authors.affiliation: Department of Biochemistry, New York University School of Medicine, New York, NY, USA. edward.ziff@nyumc.org.
authors.forename: Edward
authors.initials: E
authors.lastname: Ziff
authors.affiliation: Departments of Otolaryngology and Physiology and Neuroscience, The Helen and Martin Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, NY, USA. Robert.Froemke@med.nyu.edu.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Froemke
authors.affiliation: Department of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. huangdong6619@vip.163.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Huang
authors.affiliation: Departments of Anesthesiology, Neuroscience and Physiology, New York University School of Medicine, New York, NY, USA. Jing.wang2@nyumc.org.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D059350:Chronic Pain / Q000150:complications*; D003863:Depression / Q000209:etiology / Q000378:metabolism; D005620:Freund's Adjuvant; D007249:Inflammation / Q000150:complications; D008297:Male; D009437:Neuralgia / Q000150:complications; D009714:Nucleus Accumbens / Q000378:metabolism* / Q000473:pathology; D021122:Protein Subunits / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
chemical_list: D021122:Protein Subunits; D018091:Receptors, AMPA; D005620:Freund's Adjuvant