Transient opening of the perineurial barrier for analgesic drug delivery

  1. Hackel, Dagmar
  2. Krug, Susanne M.
  3. Sauer, Reine-Solange
  4. Mousa, Shaaban A.
  5. Böcker, Alexander
  6. Pflücke, Diana
  7. Wrede, Esther-Johanna
  8. Kistner, Katrin
  9. Hoffmann, Tali
  10. Niedermirtl, Benedikt
  11. Sommer, Claudia
  12. Bloch, Laura
  13. Huber, Otmar
  14. Blasig, Ingolf E.
  15. Amasheh, Salah
  16. Reeh, Peter W.
  17. Fromm, Michael
  18. Brack, Alexander
  19. Rittner, Heike L.

WeightNameValue
1000 Titel
  • Transient opening of the perineurial barrier for analgesic drug delivery
1000 Autor/in
  1. Hackel, Dagmar |
  2. Krug, Susanne M. |
  3. Sauer, Reine-Solange |
  4. Mousa, Shaaban A. |
  5. Böcker, Alexander |
  6. Pflücke, Diana |
  7. Wrede, Esther-Johanna |
  8. Kistner, Katrin |
  9. Hoffmann, Tali |
  10. Niedermirtl, Benedikt |
  11. Sommer, Claudia |
  12. Bloch, Laura |
  13. Huber, Otmar |
  14. Blasig, Ingolf E. |
  15. Amasheh, Salah |
  16. Reeh, Peter W. |
  17. Fromm, Michael |
  18. Brack, Alexander |
  19. Rittner, Heike L. |
1000 Erscheinungsjahr 2012
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2012-06-25
1000 Erschienen in
1000 Quellenangabe
  • 109(29): E2018 - E2027
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406837/ |
  • http://dx.doi.org/10.1073/pnas.1120800109 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Selective targeting of sensory or nociceptive neurons in peripheral nerves remains a clinically desirable goal. Delivery of promising analgesic drugs is often impeded by the perineurium, which functions as a diffusion barrier attributable to tight junctions. We used perineurial injection of hypertonic saline as a tool to open the perineurial barrier transiently in rats and elucidated the molecular action principle in mechanistic detail: Hypertonic saline acts via metalloproteinase 9 (MMP9). The noncatalytic hemopexin domain of MMP9 binds to the low-density lipoprotein receptor-related protein-1, triggers phosphorylation of extracellular signal-regulated kinase 1/2, and induces down-regulation of the barrier-forming tight junction protein claudin-1. Perisciatic injection of any component of this pathway, including MMP9 hemopexin domain or claudin-1 siRNA, enables an opioid peptide ([D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin) and a selective sodium channel (NaV1.7)-blocking toxin (ProToxin-II) to exert antinociceptive effects without motor impairment. The latter, as well as the classic TTX, blocked compound action potentials in isolated nerves only after disruption of the perineurial barrier, which, in return, allowed endoneurally released calcitonin gene-related peptide to pass through the nerve sheaths. Our data establish the function and regulation of claudin-1 in the perineurium as the major sealing component, which could be modulated to facilitate drug delivery or, potentially, reseal the barrier under pathological conditions.
1000 Sacherschließung
lokal two path impedance spectroscopy
lokal blood-nerve barrier
lokal regional anesthesia
lokal C-fiber
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
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1000 Label
1000 Förderer
  1. German Research Foundation |
  2. Else–Kröner–Fresenius Foundation |
1000 Fördernummer
  1. FOR 721/2
  2. -
1000 Förderprogramm
  1. -
  2. -
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer German Research Foundation |
    1000 Förderprogramm -
    1000 Fördernummer FOR 721/2
  2. 1000 joinedFunding-child
    1000 Förderer Else–Kröner–Fresenius Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6404880.rdf
1000 Erstellt am 2017-10-09T13:27:24.007+0200
1000 Erstellt von 122
1000 beschreibt frl:6404880
1000 Bearbeitet von 288
1000 Zuletzt bearbeitet 2022-08-18T07:51:15.860+0200
1000 Objekt bearb. Thu Apr 08 09:34:32 CEST 2021
1000 Vgl. frl:6404880
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