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Páll Karlsson
Angiotensin II triggers peripheral macrophage-to-sensory neuron redox crosstalk to elicit pain
Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review
Links
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083458/pdf/zns7032.pdf
Forlagets udgivne version
DOI
- https://doi.org/10.1523/JNEUROSCI.3542-17.2018
Forlagets udgivne version
- Andrew J Shepherd, University of Iowa ,
- Bryan A Copits, Washington University St. Louis ,
- Aaron D Mickle, University of Iowa ,
- Páll Karlsson
- Suraj Kadunganattil, Washington University St. Louis ,
- Simon Haroutounian, Washington University St. Louis ,
- Satya M Tadinada, University of Iowa ,
- Annette D de Kloet, Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL, 32610, USA. ,
- Manouela V Valtcheva, Washington University St. Louis ,
- Lisa A McIlvried, Washington University St. Louis ,
- Tayler D Sheahan, Washington University St. Louis ,
- Sanjay Jain, Washington University St. Louis ,
- Pradipta R Ray, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, 75080, USA. ,
- Yuriy M Usachev, University of Iowa ,
- Gregory Dussor, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, 75080, USA. ,
- Eric G Krause, Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA. ,
- Theodore J Price, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, 75080, USA. ,
- Robert W Gereau, Washington University St. Louis ,
- Durga P Mohapatra, Washington University St. Louis
Injury, inflammation, and nerve damage initiate a wide variety of cellular and molecular processes that culminate in hyperexcitation of sensory nerves, which underlies chronic inflammatory and neuropathic pain. Using be avioral readouts of pain hypersensitivity induced by angiotensin II (Ang II) injection into mouse hindpaws, our study shows that activation of the type 2 Ang II receptor (AT2R) and the cell-damage-sensing ion channel TRPA1 are required for peripheral mechanical pain sensitization induced by Ang II in male and female mice. However, we show that AT2R is not expressed in mouse and human dorsal root ganglia (DRG) sensory neurons. Instead, expression/ activation of AT2R on peripheral/skin macrophages (Mɸs) constitutes a critical trigger of mouse and human DRG sensory neuron excitation. Ang II-induced peripheral mechanical pain hypersensitivity can be atten ated by chemogenetic depletion of peripheralM_s. Furthermore, AT2R activation in Mɸs triggers production of reactive oxygen/nitrogen species, which trans-activate TRPA1 on mouse and human DRG sensory neurons via cysteine modification of the channel. Our study thus identifies a translatable immune cell-tosensory neuron signaling crosstalk underlying peripheral nociceptor sensitization. This form of cell-to-cell signaling represents a critical peripheral mechanism for chronic pain and thus identifies multiple druggable analgesic targets.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | The Journal of neuroscience : the official journal of the Society for Neuroscience |
| Vol/bind | 38 |
| Nummer | 32 |
| Sider (fra-til) | 7032-7057 |
| Antal sider | 26 |
| ISSN | 0270-6474 |
| DOI | |
| Status | Udgivet - 8 aug. 2018 |
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