title: P2X7 receptor in the trigeminal sensory nuclear complex contributes to tactile allodynia/hyperalgesia following trigeminal nerve injury.
abstract: BACKGROUND
  The present study directly addresses the roles of the P2X(7) receptor (P2X(7)R), an ionotropic adenosine triphosphate (ATP) receptor, and cytokines in the induction of orofacial pain following chronic constriction injury (CCI) of the infraorbital nerve (IoN).
  
  
  METHODS
  Rats were anesthetized, and ligatures of 4-0 chromic gut were tied around the IoN. A438079, a P2X(7)R antagonist or SB203580, a phosphorylated (p)-p38 mitogen-activated protein kinase (MAPK) inhibitor, was infused intrathecally into CCI-treated rats. In another group of rats, 3'-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP), a P2X(7) R agonist, was infused intrathecally with A438079, SB203580 or etanercept, a tumor necrosis factor (TNF)-α receptor-binding recombinant drug.
  
  
  RESULTS
  CCI of the IoN induced tactile allodynia/hyperalgesia and up-regulation of P2X(7)R, membrane-bound TNF-α (mTNF-α) and soluble TNF-α (sTNF-α) in the trigeminal sensory nuclear complex (TNC). Tactile allodynia/hyperalgesia or up-regulation of mTNF-α and sTNF-α in the TNC following CCI of the IoN was inhibited by A438079. SB203580 also attenuated tactile allodynia/hyperalgesia or up-regulation of mTNF-α, but not the up-regulation of sTNF-α in the TNC. Treatment of rats with BzATP induced tactile allodynia/hyperalgesia and up-regulation of sTNF-α and p-p38 in the TNC. Tactile allodynia/hyperalgesia or up-regulation of sTNF-α following BzATP treatment was inhibited by SB203580 and etanercept.
  
  
  CONCLUSIONS
  Based on these findings, phosphorylation of p38 MAPK via P2X(7)R may induce tactile allodynia/hyperalgesia, which is most likely mediated by sTNF-α released by microglia.
authors.affiliation: Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Suekawa
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Inubushi
authors.forename: K
authors.initials: K
authors.lastname: Murasaki
authors.forename: N
authors.initials: N
authors.lastname: Hirose
authors.forename: S
authors.initials: S
authors.lastname: Hiyama
authors.forename: T
authors.initials: T
authors.lastname: Uchida
authors.forename: K
authors.initials: K
authors.lastname: Tanne
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western; D001933:Brain Stem / Q000737:chemistry / Q000378:metabolism; D003251:Constriction, Pathologic; D005157:Facial Pain / Q000209:etiology / Q000503:physiopathology; D006930:Hyperalgesia / Q000503:physiopathology*; D007150:Immunohistochemistry; D007278:Injections, Spinal; D008297:Male; D017628:Microglia / Q000378:metabolism; D010525:Peripheral Nerves / Q000187:drug effects; D058911:Purinergic P2X Receptor Agonists / Q000494:pharmacology; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D058486:Receptors, Purinergic P2X7 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D061221:Trigeminal Nerve Injuries / Q000503:physiopathology*; D014278:Trigeminal Nuclei / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D058911:Purinergic P2X Receptor Agonists; D058920:Purinergic P2X Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases