title: Intraganglionic injection of a nitric oxide donator induces afferent mechanical sensitization that is attenuated by palmitoylethanolamide.
abstract: OBJECTIVE
  The aim of this article is to investigate whether the nitric oxide (NO) donator diethylenetriamine/nitric oxide (DETA/NO) affects trigeminal sensory processing through the trigeminal ganglion in part by activating trigeminal satellite glial cells (SGCs) and whether this effect is attenuated by the anti-inflammatory compound palmitoylethanolamide (PEA).
  
  
  METHODS
  DETA/NO was administered to isolated rat trigeminal SGCs in vitro, and injected into the rat trigeminal ganglion in vivo, in the presence or absence of PEA.
  
  
  RESULTS
  Administration of DETA/NO (1000 µM) increased the release of prostaglandin E2by SGCs. PEA (1 and 10 µM) significantly attenuated prostaglandin E2release. Two intraganglionic injections of DETA/NO (10 mM, 3 µl) or prostaglandin E2at a 30-minute interval did not evoke discharge in trigeminal ganglion neurons that innervate the rat jaw-closer muscles, but did reduce the mechanical activation threshold of their peripheral endings by 30%-50%. Intravenous administration of PEA (1 mg/kg) or ketorolac (0.5 mg/kg) prevented DETA/NO-induced afferent mechanical sensitization.
  
  
  CONCLUSIONS
  Elevation of NO in the trigeminal ganglion results in the sensitization of the peripheral endings of masticatory muscle nociceptors to mechanical stimulation through a mechanism that involves prostaglandin E2release from SGCs. Attenuation of this sensitization by PEA suggests a possible option for acute management of craniofacial pain and headache.
authors: Center for Sensory-Motor Interaction, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Denmark Faculty of Pharmaceutical Sciences, The University of British Columbia, Canada.
authors: Brian E
authors: BE
authors: Cairns
authors: Center for Sensory-Motor Interaction, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Denmark.
authors: Jens C
authors: JC
authors: Laursen
authors: Faculty of Pharmaceutical Sciences, The University of British Columbia, Canada College of Stomatology, Tianjin Medical University, PR China.
authors: Xu-Dong
authors: XD
authors: Dong
authors: Center for Sensory-Motor Interaction, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Denmark gazerani@hst.aau.dk.
authors: Parisa
authors: P
authors: Gazerani
keywords: Headache; glial modulators; nitric oxide; palmitoylethanolamide; satellite glial cells; trigeminal ganglion