title: Central nervous system mast cells in peripheral inflammatory nociception.
abstract: BACKGROUND
  Functional aspects of mast cell-neuronal interactions remain poorly understood. Mast cell activation and degranulation can result in the release of powerful pro-inflammatory mediators such as histamine and cytokines. Cerebral dural mast cells have been proposed to modulate meningeal nociceptor activity and be involved in migraine pathophysiology. Little is known about the functional role of spinal cord dural mast cells. In this study, we examine their potential involvement in nociception and synaptic plasticity in superficial spinal dorsal horn. Changes of lower spinal cord dura mast cells and their contribution to hyperalgesia are examined in animal models of peripheral neurogenic and non-neurogenic inflammation.
  
  
  RESULTS
  Spinal application of supernatant from activated cultured mast cells induces significant mechanical hyperalgesia and long-term potentiation (LTP) at spinal synapses of C-fibers. Lumbar, thoracic and thalamic preparations are then examined for mast cell number and degranulation status after intraplantar capsaicin and carrageenan. Intradermal capsaicin induces a significant percent increase of lumbar dural mast cells at 3 hours post-administration. Peripheral carrageenan in female rats significantly increases mast cell density in the lumbar dura, but not in thoracic dura or thalamus. Intrathecal administration of the mast cell stabilizer sodium cromoglycate or the spleen tyrosine kinase (Syk) inhibitor BAY-613606 reduce the increased percent degranulation and degranulated cell density of lumbar dural mast cells after capsaicin and carrageenan respectively, without affecting hyperalgesia.
  
  
  CONCLUSIONS
  The results suggest that lumbar dural mast cells may be sufficient but are not necessary for capsaicin or carrageenan-induced hyperalgesia.
authors.affiliation: Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Vienna, Austria. juergen.sandkuehler@meduniwien.ac.at.
authors.forename: Dimitris N
authors.initials: DN
authors.lastname: Xanthos
authors.forename: Simon
authors.initials: S
authors.lastname: Gaderer
authors.forename: Ruth
authors.initials: R
authors.lastname: Drdla
authors.forename: Erin
authors.initials: E
authors.lastname: Nuro
authors.forename: Anastasia
authors.initials: A
authors.lastname: Abramova
authors.forename: Wilfried
authors.initials: W
authors.lastname: Ellmeier
authors.forename: Jürgen
authors.initials: J
authors.lastname: Sandkühler
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002351:Carrageenan; D002452:Cell Count; D015550:Cell Degranulation / Q000187:drug effects; D002490:Central Nervous System / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006930:Hyperalgesia / Q000150:complications / Q000473:pathology; D017774:Long-Term Potentiation / Q000187:drug effects; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000473:pathology; D020078:Neurogenic Inflammation / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects; D013788:Thalamus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D002351:Carrageenan; D002211:Capsaicin