title: Experiencing neonatal maternal separation increased pain sensitivity in adult male mice: Involvement of oxytocinergic system.
abstract: Early-life stress adversely affects the development of the brain, and alters a variety of behaviors such as pain in later life. In present study, we investigated how early-life stress (maternal separation or MS) can affect the nociceptive response later in life. We particularly focused on the role of oxytocin (OT) in regulating nociception in previously exposed (MS during early postnatal development) mice that were subjected to acute stress (restraint stress or RS). Further, we evaluated whether such modulation of pain sensation in MS mice are regulated by shared mechanisms of the OTergic and opioidergic systems. To do this, we assessed the underlying systems mediating the nociceptive response by administrating different antagonists (for both opioid and OTergic systems) under the different experimental conditions (control vs MS, and control plus RS vs MS plus RS). Our results showed that MS increased pain sensitivity in both tail-flick and hot-plate tests while after administration of OT (1μg/μl/mouse, i.c.v) pain threshold was increased. Atosiban, an OT antagonist (10μg/μl/mouse, i.c.v) abolished the effects of OT. While acute RS increased the pain threshold in control (and not MS) mice, treating MS mice with OT normalized the pain response to RS. This latter effect was reversed by atosiban and/or naltrexone, an opioid antagonist (0.5μg/μl/mouse, i.c.v) suggesting that OT enhances the effect of endogenous opioids. OTergic system is involved in mediating the nociception under acute stress in mice subjected to early-life stress and OTergic and opioidergic systems interact to modulate pain sensitivity in MS mice.
authors.affiliation: Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran; Department of Physiology and Pharmacology, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Amini-Khoei
authors.affiliation: Regenerative Medicine Program, Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Shayan
authors.initials: S
authors.lastname: Amiri
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Mohammadi-Asl
authors.affiliation: Department of Biology, Faculty of Sciences, Gonbad Kavous University, Gonbad, Iran.
authors.forename: Sakineh
authors.initials: S
authors.lastname: Alijanpour
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Simin
authors.initials: S
authors.lastname: Poursaman
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box: 13145-784, Tehran, Iran.
authors.forename: Arya
authors.initials: A
authors.lastname: Haj-Mirzaian
authors.affiliation: Regenerative Medicine Program, Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Rastegar
authors.affiliation: Department of Pharmacology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
authors.forename: Azam
authors.initials: A
authors.lastname: Mesdaghinia
authors.affiliation: Department of Pharmacology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran.
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Banafshe
authors.affiliation: Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, P.O. Box: 13145-784, Tehran, Iran.
authors.forename: Ehsanollah
authors.initials: E
authors.lastname: Sadeghi
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Elika
authors.initials: E
authors.lastname: Samiei
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box: 13145-784, Tehran, Iran.
authors.forename: Shahram Ejtemaie
authors.initials: SE
authors.lastname: Mehr
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box: 13145-784, Tehran, Iran. Electronic address: dehpour@yahoo.com.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D008426:Maternal Deprivation; D051379:Mice; D009271:Naltrexone / Q000494:pharmacology; D010121:Oxytocin / Q000502:physiology*; D010146:Pain / Q000378:metabolism / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000701:Analgesics, Opioid; D006727:Hormone Antagonists; C047046:atosiban; D010121:Oxytocin; D009271:Naltrexone; D014668:Vasotocin
keywords: Acute restraint stress; Maternal separation; Opioid; Oxytocin; Pain threshold