title: PKCγ-positive neurons gate light tactile inputs to pain pathway through pERK1/2 neuronal network in trigeminal neuropathic pain model.
abstract: OBJECTIVE
  To explore the possible relationship between protein kinase C gamma (PKCγ) and phosphorylated forms of extracellular signal-regulated kinases 1/2 (pERK1/2) in the rat medullary dorsal horn and the facial hypersensitivity indicative of dynamic mechanical allodynia (DMA) following chronic constriction of the infraorbital nerve (CCI-IoN).
  
  
  METHODS
  A well-established rat model of trigeminal neuropathic pain involving CCI-IoN was used. Facial mechanical hypersensitivity was tested with non-noxious dynamic mechanical stimulation (air-puff), and the medullary dorsal horn was examined immunohistochemically using PKCγ and pERK1/2 as pain markers. Statistical analysis was performed using Student t test or one-way analysis of variance (ANOVA).
  
  
  RESULTS
  Increased PKCγ and pERK1/2 expressions within the medullary dorsal horn were associated with DMA following CCI-IoN. A segmental network composed of PKCγ-positive cells located in medullary dorsal horn laminae II/III, contacting more superficially located pERK1/2-expressing cells, was identified. Ultrastructural analysis confirmed the presence of PKCγ to pERK1/2-positive cells. Moreover, intracisternal administration of the selective PKCγ inhibitor KIG31-I blocked both the DMA and pERK1/2 expression in a dose-dependent manner. Although the number of pERK1/2-positive cells was significantly elevated with air-puff stimulation, DMA rats not receiving air-puff stimulation showed significant pERK1/2 expression, suggesting they were experiencing spontaneous pain.
  
  
  CONCLUSIONS
  PKCγ cells in the medullary dorsal horn may be involved in DMA following CCI-IoN through the activation of pERK1/2-expressing cells, which then may relay non-nociceptive information to lamina I cells in the medullary dorsal horn.
authors: Wisam
authors: W
authors: Dieb
authors: Pedro
authors: P
authors: Alvarez
authors: Aziz
authors: A
authors: Hafidi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000032:analysis / Q000502:physiology*; D005157:Facial Pain / Q000201:enzymology / Q000503:physiopathology; D006930:Hyperalgesia / Q000201:enzymology / Q000503:physiopathology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D009434:Neural Pathways / Q000201:enzymology / Q000503:physiopathology / Q000648:ultrastructure; D059225:Nociception / Q000502:physiology*; D009915:Orbit / Q000294:innervation; D010766:Phosphorylation; D020671:Posterior Horn Cells / Q000201:enzymology* / Q000502:physiology / Q000648:ultrastructure; D011493:Protein Kinase C / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014110:Touch / Q000502:physiology*; D014277:Trigeminal Neuralgia / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D007527:Isoenzymes; C087857:protein kinase C gamma; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases