title: Central sensitization and MAPKs are involved in occlusal interference-induced facial pain in rats.
abstract: We previously developed a rat dental occlusal interference model of facial pain that was produced by bonding a crown onto the right maxillary first molar and was reflected in sustained facial hypersensitivity that was suggestive of the involvement of central sensitization mechanisms. The aim of the present study was to investigate potential central mechanisms involved in the occlusal interference-induced facial hypersensitivity. A combination of behavioral, immunohistochemical, Western blot, and electrophysiological recording procedures was used in 98 male adult Sprague Dawley rats that either received the occlusal interference or were sham-operated or naive rats. Immunohistochemically labeled astrocytes and microglia in trigeminal subnucleus caudalis (Vc) showed morphological changes indicative of astrocyte and microglial activation after the occlusal interference. Prolonged upregulation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) was also documented in Vc after placement of the occlusal interference and was expressed in both neurons and glial cells at time points when rats showed peak mechanical facial hypersensitivity. The intrathecal administration of the p38 MAPK inhibitor SB203580 to the medulla significantly inhibited the occlusal interference-induced hypersensitivity, and the ERK inhibitor PD98059 produced an even stronger effect. Central sensitization of functionally identified Vc nociceptive neurons following placement of the occlusal interference was also documented by extracellular electrophysiological recordings, and intrathecal administration of PD98059 could reverse the neuronal central sensitization. These novel findings suggest that central mechanisms including central sensitization of trigeminal nociceptive neurons and non-neuronal processes involving MAPKs play significant roles in the production of occlusal interference-induced facial pain.
  
  
  CONCLUSIONS
  Central mechanisms including trigeminal nociceptive neuronal sensitization, non-neuronal processes involving glial activation, and MAPKs play significant roles in occlusal interference-induced facial pain. These mechanisms may be involved in clinical manifestations of facial pain that have been reported in patients with an occlusal interference.
authors: Department of Prosthodontics, Peking University School & Hospital of Stomatology, Beijing, PR China.
authors: Ye
authors: Y
authors: Cao
authors: Kai
authors: K
authors: Li
authors: Kai-Yuan
authors: KY
authors: Fu
authors: Qiu-Fei
authors: QF
authors: Xie
authors: Chen-Yu
authors: CY
authors: Chiang
authors: Barry J
authors: BJ
authors: Sessle
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D059333:Central Nervous System Sensitization / Q000187:drug effects / Q000502:physiology*; D003766:Dental Occlusion; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005157:Facial Pain / Q000201:enzymology* / Q000209:etiology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009457:Neuroglia / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014278:Trigeminal Nuclei / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D020929:Mitogen-Activated Protein Kinase Kinases; D010751:Phosphopyruvate Hydratase
keywords: Occlusal interference; central sensitization; glia; hypersensitivity; mitogen-activated protein kinases; trigeminal subnucleus caudalis
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