title: Mechanisms involved in an increment of multimodal excitability of medullary and upper cervical dorsal horn neurons following cutaneous capsaicin treatment.
abstract: BACKGROUND
  In order to evaluate mechanisms that may underlie the sensitization of trigeminal spinal subnucleus caudalis (Vc; the medullary dorsal horn) and upper cervical spinal cord (C1-C2) nociceptive neurons to heat, cold and mechanical stimuli following topical capsaicin treatment of the facial skin, nocifensive behaviors as well as phosphorylation of extracellular regulated-kinase (pERK) in Vc and C1-C2 neurons were studied in rats.
  
  
  RESULTS
  Compared to vehicle application, capsaicin application to the lateral facial skin produced 1 hour later a flare in the skin, and also induced significantly greater nocifensive behaviors to heat, cold or mechanical stimulus of the lateral facial skin. The intrathecal (i.t.) injection of the MEK inhibitor PD98059 markedly attenuated the nocifensive behaviors to these stimuli in capsaicin-treated rats. Moreover, the number of pERK-like immunoreactive (pERK-LI) cells in Vc and C1-C2 was significantly larger following the heat, cold and mechanical stimuli in capsaicin-treated rats compared with vehicle-treated rats. The number of pERK-LI cells gradually increased following progressive increases in the heat or mechanical stimulus intensity and following progressive decrease in the cold stimulus. The ERK phosphorylation in Vc and C1-C2 neurons was strongly inhibited after subcutaneous injection of the capsaicin antagonist capsazepine in capsaicin-treated rats.
  
  
  CONCLUSIONS
  The present findings revealed that capsaicin treatment of the lateral facial skin causes an enhancement of ERK phosphorylation in Vc and C1-C2 neurons as well as induces nocifensive behavior to heat, cold and mechanical simulation of the capsaicin-treated skin. The findings suggest that TRPV1 receptor mechanisms in rat facial skin influence nociceptive responses to noxious cutaneous thermal and mechanical stimuli by inducing neuroplastic changes in Vc and C1-C2 neurons that involve in the MAP kinase cascade.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nihon University School of Dentistry, Kandasurugadai, Chiyoda-ku Tokyo, Japan. honda-kn@dent.nihon-u.ac.jp
authors.forename: Kuniya
authors.initials: K
authors.lastname: Honda
authors.forename: Junichi
authors.initials: J
authors.lastname: Kitagawa
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Sessle
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kondo
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tsuboi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yonehara
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D003080:Cold Temperature / Q000009:adverse effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006358:Hot Temperature / Q000009:adverse effects; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010146:Pain / Q000201:enzymology / Q000503:physiopathology*; D010766:Phosphorylation; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology; D018689:Sensory System Agents / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013697:Thermosensing / Q000187:drug effects / Q000502:physiology; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*
chemical_list: D018689:Sensory System Agents; D048049:Extracellular Signal-Regulated MAP Kinases; D002211:Capsaicin