title: Maternal Separation Induces Orofacial Mechanical Allodynia in Adulthood.
abstract: It is well known that exposure to maternal separation (MS) in early life causes plastic changes in the nervous system in adulthood, occasionally resulting in ubiquitous chronic pain. However, the pathogenic mechanisms of pain hypersensitivity remain unclear. Here, the authors examined the involvement of corticosterone in orofacial mechanical hypersensitivity induced by MS. To establish a rat model of MS, pups were placed in isolated cages 180 min/d and kept in a temperature-controlled environment at 22 ± 2 °C for 14 d. Mechanical allodynia in the whisker pad skin in adulthood was induced by MS and was significantly suppressed by successive postnatal subcutaneous administration of the glucocorticoid receptor antagonist mifepristone. Corticosterone levels were increased in the serum of MS rats, and successive postnatal administration of subcutaneous corticosterone to naive rats induced mechanical allodynia in the whisker pad skin. The number of P2X3 receptor-immunoreactive (P2X3R-IR) trigeminal ganglion (TG) neurons innervating the whisker pad skin was significantly increased in MS rats and decreased following subcutaneous administration of mifepristone. The number of P2X3R-IR TG neurons innervating the whisker pad skin was also significantly increased following successive postnatal administration of subcutaneous corticosterone in naive rats. Moreover, the mechanical allodynia was suppressed 30 min after administration of the P2X3R antagonist A317491 to the whisker pad skin in MS rats. These findings suggest that the increase in P2X3R-IR TG neurons innervating the whisker pad skin via enhanced neonatal corticosterone signaling by MS plays an important role in orofacial mechanical allodynia in adulthood.
authors.affiliation: Department of Oral Function and Restoration, Division of Pediatric Dentistry, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yasuda
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan shinoda.masamichi@nihon-u.ac.jp.
authors.forename: M
authors.initials: M
authors.lastname: Shinoda
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of Oral Function and Restoration, Division of Pediatric Dentistry, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fujita
authors.affiliation: Department of Histology, Embryology and Neuroanatomy, Kanagawa Dental University, Yokosuka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kawata
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan Department of Periodontology, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nagashima
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan Department of Periodontology, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Division of Oral Diagnosis, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Shoji
authors.affiliation: Department of Histology, Embryology and Neuroanatomy, Kanagawa Dental University, Yokosuka, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Takahashi
authors.affiliation: Department of Oral Function and Restoration, Division of Pediatric Dentistry, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kimoto
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan Division of Applied System Neuroscience Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000305:Adrenal Cortex Hormones / Q000097:blood / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005157:Facial Pain / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006930:Hyperalgesia / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008426:Maternal Deprivation; D015735:Mifepristone / Q000494:pharmacology; D017288:Pain Threshold; D051381:Rats; D017207:Rats, Sprague-Dawley; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000378:metabolism / Q000473:pathology; D014738:Vibrissae / Q000294:innervation
chemical_list: D000305:Adrenal Cortex Hormones; D058477:Receptors, Purinergic P2X3; D015735:Mifepristone
keywords: child abuse; corticosterone; glucocorticoid receptor; orofacial pain; p2x3 receptor; trigeminal ganglion