title: Persistent nociception induces anxiety-like behavior in rodents: role of endogenous neuropeptide S.
abstract: Anxiety disorder is a comorbid condition of chronic pain. Analgesics and anxiolytics, subject to addiction and abuse, are currently used to manage pain and anxiety symptoms. However, the cellular mechanism underlying chronic pain and anxiety interaction remains to be elucidated. We report that persistent nociception following peripheral nerve injury induced anxiety-like behavior in rodents. Brain expression and release of neuropeptide S (NPS), a proposed endogenous anxiolytic peptide, was diminished in rodents with coexisting nociceptive and anxiety-like behaviors. Intracerebroventricular administration of exogenous NPS concurrently improved both nociceptive and anxiety-like behaviors. At the cellular level, NPS enhanced intra-amygdaloidal inhibitory transmission by increasing presynaptic gamma-aminobutyric acid (GABA) release from interneurons. These findings indicate that the interaction between nociceptive and anxiety-like behaviors in rodents may be regulated by the altered NPS-mediated intra-amygdaloidal GABAergic inhibition. The data suggest that enhancing the brain NPS function may be a new strategy to manage comorbid pain and anxiety.
authors.affiliation: MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA Department of Anesthesia and Pain Therapy, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China.
authors.forename: Shuzhuo
authors.initials: S
authors.lastname: Zhang
authors.forename: Xu
authors.initials: X
authors.lastname: Jin
authors.forename: Zerong
authors.initials: Z
authors.lastname: You
authors.forename: Shuxing
authors.initials: S
authors.lastname: Wang
authors.forename: Grewo
authors.initials: G
authors.lastname: Lim
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Yang
authors.forename: Michael
authors.initials: M
authors.lastname: McCabe
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: John
authors.initials: J
authors.lastname: Marota
authors.forename: Lucy
authors.initials: L
authors.lastname: Chen
authors.forename: Jianren
authors.initials: J
authors.lastname: Mao
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D059225:Nociception / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D009479:Neuropeptides; C534458:neuropeptide S, rat; D005680:gamma-Aminobutyric Acid
keywords: Amygdala; Anxiety; Chronic pain; GABA; NPS; Neuropeptide S