title: Activation of cyclin-dependent kinase 5 mediates orofacial mechanical hyperalgesia.
abstract: BACKGROUND
  Cyclin-dependent kinase 5 (Cdk5) is a unique member of the serine/threonine kinase family. This kinase plays an important role in neuronal development, and deregulation of its activity leads to neurodegenerative disorders. Cdk5 also serves an important function in the regulation of nociceptive signaling. Our previous studies revealed that the expression of Cdk5 and its activator, p35, is upregulated in nociceptive neurons during peripheral inflammation. The aim of the present study was to characterize the involvement of Cdk5 in orofacial pain. Since mechanical hyperalgesia is the distinctive sign of many orofacial pain conditions, we adapted an existing orofacial stimulation test to assess the behavioral responses to mechanical stimulation in the trigeminal region of the transgenic mice with either reduced or increased Cdk5 activity.
  
  
  RESULTS
  Mice overexpressing or lacking p35, an activator of Cdk5, showed altered phenotype in response to noxious mechanical stimulation in the trigeminal area. Mice with increased Cdk5 activity displayed aversive behavior to mechanical stimulation as indicated by a significant decrease in reward licking events and licking time. The number of reward licking/facial contact events was significantly decreased in these mice as the mechanical intensity increased. By contrast, mice deficient in Cdk5 activity displayed mechanical hypoalgesia.
  
  
  CONCLUSIONS
  Collectively, our findings demonstrate for the first time the important role of Cdk5 in orofacial mechanical nociception. Modulation of Cdk5 activity in primary sensory neurons makes it an attractive potential target for the development of novel analgesics that could be used to treat multiple orofacial pain conditions.
authors.forename: Michaela
authors.initials: M
authors.lastname: Prochazkova
authors.forename: Anita
authors.initials: A
authors.lastname: Terse
authors.forename: Niranjana D
authors.initials: ND
authors.lastname: Amin
authors.forename: Bradford
authors.initials: B
authors.lastname: Hall
authors.forename: Elias
authors.initials: E
authors.lastname: Utreras
authors.forename: Harish C
authors.initials: HC
authors.lastname: Pant
authors.affiliation: Functional Genomics Section, Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. ak40m@nih.gov.
authors.forename: Ashok B
authors.initials: AB
authors.lastname: Kulkarni
mesh_terms: D000818:Animals; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism*; D005157:Facial Pain / Q000201:enzymology / Q000378:metabolism; D006930:Hyperalgesia / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D012668:Trigeminal Ganglion / Q000201:enzymology / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; C089495:neuronal Cdk5 activator (p25-p35); D051360:Cyclin-Dependent Kinase 5