Startseite Glial cells as target for antidepressants in neuropathic pain
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Glial cells as target for antidepressants in neuropathic pain

  • Elisa Damo

    Elisa Damo received her M.Sc. in Molecular Biology/Neurobiology from the University of Torino in 2019. Currently, she is pursuing her PhD at Heidelberg in the group of Manuela Simonetti in the department of Prof. Rohini Kuner at the Pharmacology Institute. Her research field covers neuropathic pain, glial biology, and cell signaling.

     ORCID logo     , Phillip Rieder

    Phillip Rieder received his M.Sc. in Human- and Molecular Biology at University of Saarland in 2017. His PhD work addresses the role of glial Ca2+ signaling in the spinal cord and dorsal root ganglia.

     ORCID logo     , Ilknur Coban

    Ilknur Coban is currently a PhD in Agarwal laboratory at the Anatomy and Cell Biology Institute of Heidelberg University, Germany. Her research interests are physiology of astrocytes, glia-neuron interactions, and neuropathic pain.

     ORCID logo     , Rangel Leal Silva

    Rangel Leal Silva is currently working as postdoctoral fellow in the Agarwal laboratory at the Institute of Anatomy and Molecular Biology of Heidelberg University. His research interest is toward the understanding of the role of neuron-glia-immune interaction in neurological disorders, currently focusing on chronic pain.

     ORCID logo     , Frank Kirchhoff

    Frank Kirchhoff received his PhD (Dr. rer. nat.) degree from Heidelberg University. Since 2009, he is full professor of molecular physiology at the University of Saarland in Homburg. His research focuses on the molecular and cellular mechanisms of neuron-glia interactions.

     ORCID logo     , Manuela Simonetti

    Manuela Simonetti received her PhD in Neuroscience at SISSA (Triste, Italy). Currently, she is a senior scientist and Principal Investigator (CRC1158) in the laboratory of Prof. Rohini Kuner at the Institute of Pharmacology, University of Heidelberg, working in molecular-cellular neurobiology and neurophysiology, focusing her attention on pain transmission.

     ORCID logo EMAIL logo     und Amit Agarwal

    Amit Agarwal received his Ph.D. in neurosciences, at the Max-Planck-Institute of Experimental Medicine, Göttingen. He did his post-doctoral training in the Department of Neuroscience at the Johns Hopkins University, USA. Since 2018, he is an independent group leader funded by the Chica and Heinz Schaller Foundation at the Heidelberg University. His laboratory uses in vivo multiphoton microscopy, single-cell genetics, mouse transgenics, and AI-based computational methodologies to decipher cellular connectivity and molecular pathways by which neurons and glia interact, interconnect and integrate into the neural networks in the context of health and disease (including pain).

     ORCID logo EMAIL logo
Veröffentlicht/Copyright: 24. März 2022
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Aus der Zeitschrift Neuroforum Band 28 Heft 2

Abstract

Several forms of chronic pain do not respond to the conventional analgesics, such as opioids, but can be treated with antidepressants, such as serotonin and noradrenalin reuptake inhibitors (SNRIs). Recent studies indicate that noradrenalin signalling is a key target for SNRI-induced analgesia in neuropathic pain. SNRIs inhibit chronic pain by blocking reuptake of noradrenalin and subsequent activation of adrenergic receptors on neurons in the dorsal horn of the spinal cord. However, in the nervous system, various subtypes of adrenergic receptors are highly expressed by astrocytes and microglial cells. Activation of these receptors on astrocytes engages complex intracellular signalling pathways and prevents inflammatory changes of microglia, which in turn can affect neuronal activity. Hence, SNRIs-induced modulations of the glial cell physiology can impact neural circuit functions and pain perception. In this review, we summarize our current knowledge on the impact of SNRIs on glial cells and in modulating chronic pain in experimental animal models.

Zusammenfassung

Konventionelle Analgetika wie Opioide helfen häufig nicht bei chronischen Schmerzen, interessanterweise im Gegensatz zu Antidepressiva wie Serotonin- und Noradrenalin-Wiederaufnahmehemmern (SNRI). Neuere Untersuchungen zeigen nun, dass in der Tat Noradrenalin-abhängige Signalwege bei SNRI-induzierter Analgesie beteiligt sind. SNRIs induzieren erhöhte Noradrenalin-Spiegel im Dorsalhorn des Rückenmarks. Die folgende Aktivierung adrenerger Rezeptoren der Spinalneurone führt zu einer deutlichen Reduktion der neuropathischen Schmerzen. Im Nervensystem werden jedoch verschiedene Subtypen von adrenergen Rezeptoren in hohem Maße von Astrozyten und Mikrogliazellen exprimiert. Die Aktivierung dieser Rezeptoren auf Astrozyten setzt komplexe intrazelluläre Signalwege in Gang und verhindert entzündliche Veränderungen der Mikroglia, die ihrerseits die neuronale Aktivität beeinflussen können. Daher können SNRI-induzierte Modulationen der Gliazellphysiologie die Funktionen neuronaler Schaltkreise und die Schmerzwahrnehmung beeinflussen. In dieser Übersicht fassen wir unser aktuelles Wissen über die Auswirkungen von SNRIs auf Gliazellen und die Modulation chronischer Schmerzen in experimentellen Tiermodellen zusammen.

Keywords: adrenergic receptors; astrocytes; chronic pain; microglia; serotonin and norepinephrine reuptake inhibitors (SNRI)
Schlüsselwörter: chronischer Schmerz; adrenerge Rezeptoren; Astrozyten; Mikrogliazellen; Noradrenalin; Serotonin- und Noradrenalin-Wiederaufnahmehemmer (SNRI)
Corresponding authors: Dr. Manuela Simonetti, Institute of Pharmacology, Medical Faculty Heidelberg, Heidelberg University, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany, E-mail: ; and Dr. Amit Agarwal, Institute of Anatomy and Cell Biology, The Chica and Heinz Schaller Research Group, Heidelberg University, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany; and Interdisciplinary Center for Neurosciences, Heidelberg University, 69120 Heidelberg, Germany, E-mail:

Funding source: The Chica and Heinz Schaller Foundation Grant

Funding source: Deutsche Forschungsgemeinschaft – SFB1158

Award Identifier / Grant number: Project A09

About the authors

Elisa Damo

Elisa Damo received her M.Sc. in Molecular Biology/Neurobiology from the University of Torino in 2019. Currently, she is pursuing her PhD at Heidelberg in the group of Manuela Simonetti in the department of Prof. Rohini Kuner at the Pharmacology Institute. Her research field covers neuropathic pain, glial biology, and cell signaling.

Phillip Rieder

Phillip Rieder received his M.Sc. in Human- and Molecular Biology at University of Saarland in 2017. His PhD work addresses the role of glial Ca2+ signaling in the spinal cord and dorsal root ganglia.

Ilknur Coban

Ilknur Coban is currently a PhD in Agarwal laboratory at the Anatomy and Cell Biology Institute of Heidelberg University, Germany. Her research interests are physiology of astrocytes, glia-neuron interactions, and neuropathic pain.

Rangel Leal Silva

Rangel Leal Silva is currently working as postdoctoral fellow in the Agarwal laboratory at the Institute of Anatomy and Molecular Biology of Heidelberg University. His research interest is toward the understanding of the role of neuron-glia-immune interaction in neurological disorders, currently focusing on chronic pain.

Frank Kirchhoff

Frank Kirchhoff received his PhD (Dr. rer. nat.) degree from Heidelberg University. Since 2009, he is full professor of molecular physiology at the University of Saarland in Homburg. His research focuses on the molecular and cellular mechanisms of neuron-glia interactions.

Manuela Simonetti

Manuela Simonetti received her PhD in Neuroscience at SISSA (Triste, Italy). Currently, she is a senior scientist and Principal Investigator (CRC1158) in the laboratory of Prof. Rohini Kuner at the Institute of Pharmacology, University of Heidelberg, working in molecular-cellular neurobiology and neurophysiology, focusing her attention on pain transmission.

Amit Agarwal

Amit Agarwal received his Ph.D. in neurosciences, at the Max-Planck-Institute of Experimental Medicine, Göttingen. He did his post-doctoral training in the Department of Neuroscience at the Johns Hopkins University, USA. Since 2018, he is an independent group leader funded by the Chica and Heinz Schaller Foundation at the Heidelberg University. His laboratory uses in vivo multiphoton microscopy, single-cell genetics, mouse transgenics, and AI-based computational methodologies to decipher cellular connectivity and molecular pathways by which neurons and glia interact, interconnect and integrate into the neural networks in the context of health and disease (including pain).

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscripts and approved submission.

  2. Research funding: This work was in part supported by the Deutsche Forschungsgemeinschaft in form of a SFB1158 grant (Project A09), and the Chica and Heinz Schaller Foundation (to AA).

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Published Online: 2022-03-24
Published in Print: 2022-05-25

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Editorial
  4. Review articles
  5. Genetics meets function in sodium channel-related pain disorders
  6. The role of neuroimmune interactions in musculoskeletal pain
  7. Glial cells as target for antidepressants in neuropathic pain
  8. Brain-based interventions for chronic pain
  9. Pain, the brain, and SARS-CoV-2: evidence for pain-specific alterations in brain-related structure–function properties
  10. Obituary
  11. Hans-Joachim Pflüger – scientist, citizen, cosmopolitan
  12. Nachrichten aus der Gesellschaft
  13. Nachrichten aus der Gesellschaft
https://doi.org/10.1515/nf-2021-0036
Schlagwörter für diesen Artikel
adrenergic receptors; astrocytes; chronic pain; microglia; serotonin and norepinephrine reuptake inhibitors (SNRI)

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Editorial
  4. Review articles
  5. Genetics meets function in sodium channel-related pain disorders
  6. The role of neuroimmune interactions in musculoskeletal pain
  7. Glial cells as target for antidepressants in neuropathic pain
  8. Brain-based interventions for chronic pain
  9. Pain, the brain, and SARS-CoV-2: evidence for pain-specific alterations in brain-related structure–function properties
  10. Obituary
  11. Hans-Joachim Pflüger – scientist, citizen, cosmopolitan
  12. Nachrichten aus der Gesellschaft
  13. Nachrichten aus der Gesellschaft
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