title: Experimental inflammation following dural application of complete Freund's adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage.
abstract: BACKGROUND
  Migraine is a paroxysmal, disabling primary headache that affects 16 % of the adult population. In spite of decades of intense research, the origin and the pathophysiology mechanisms involved are still not fully known. Although triptans and gepants provide effective relief from acute migraine for many patients, their site of action remains unidentified. It has been suggested that during migraine attacks the leakiness of the blood-brain barrier (BBB) is altered, increasing the passage of anti-migraine drugs. This study aimed to investigate the effect of experimental inflammation, following dural application of complete Freund's adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage.
  
  
  METHODS
  In order to address this issue, we induced local inflammation in male Sprague-Dawley-rats dura mater by the addition of CFA or IS directly on the dural surface. Following 2, 24 or 48 h of inflammation we calculated permeability-surface area product (PS) for [(51)Cr]-EDTA in the trigeminal ganglion (TG), spinal trigeminal nucleus, cortex, periaqueductal grey and cerebellum.
  
  
  RESULTS
  We observed that [(51)Cr]-EDTA did not pass into the central nervous system (CNS) in a major way. However, [(51)Cr]-EDTA readily passed the TG by >30 times compared to the CNS. Application of CFA or IS did not show altered transfer constants.
  
  
  CONCLUSIONS
  With these experiments we show that dural IS/CFA triggered TG inflammation, did not increase the BBB passage, and that the TG is readily exposed to circulating molecules. The TG could provide a site of anti-migraine drug interaction with effect on the trigeminal system.
authors.affiliation: Department of Medicine, Institute of Clinical Sciences, University Hospital, Lund University, 22185, Lund, Sweden.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lundblad
authors.affiliation: Department of Clinical Experimental Research, Copenhagen University Hospital, Glostrup, Denmark.
authors.forename: Kristian A
authors.initials: KA
authors.lastname: Haanes
authors.affiliation: Department of Medicine, Institute of Clinical Sciences, University Hospital, Lund University, 22185, Lund, Sweden.
authors.forename: Gustaf
authors.initials: G
authors.lastname: Grände
authors.affiliation: Department of Medicine, Institute of Clinical Sciences, University Hospital, Lund University, 22185, Lund, Sweden. Lars.Edvinsson@med.lu.se.|Department of Clinical Experimental Research, Copenhagen University Hospital, Glostrup, Denmark. Lars.Edvinsson@med.lu.se.
authors.forename: Lars
authors.initials: L
authors.lastname: Edvinsson
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004388:Dura Mater / Q000187:drug effects* / Q000503:physiopathology; D004492:Edetic Acid / Q000378:metabolism; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008881:Migraine Disorders / Q000139:chemically induced / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D005620:Freund's Adjuvant; D004492:Edetic Acid
keywords: Complete Freund’s Adjuvant; Inflammatory soup; Microvascular passage; Transfer constant; Trigeminal ganglion