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Partial sciatic nerve ligation leads to an upregulation of Ni2+-resistant T-type Ca2+ currents in capsaicin-responsive nociceptive dorsal root ganglion neurons

Authors Jeub M, Taha O, Opitz T, Racz I, Pitsch J, Becker A, Beck H

Received 7 April 2017

Accepted for publication 9 November 2018

Published 11 February 2019 Volume 2019:12 Pages 635—647


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr E Alfonso Romero-Sandoval

Monika Jeub,1,2,* Omneya Taha,1,2,* Thoralf Opitz,2 Ildiko Racz,3,4 Julika Pitsch,5 Albert Becker,5 Heinz Beck2

1Department of Neurology, University of Bonn Medical Center, Bonn, Germany; 2Department of Epileptology, University of Bonn Medical Center, Bonn, Germany; 3Institute of Molecular Psychiatry, University of Bonn Medical Center, Bonn, Germany; 4Department of Neurodegenerative Diseases and Gerontopsychiatry, University of Bonn Medical Center, Bonn, Germany; 5Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany

*These authors contributed equally to this work

Background: Neuropathic pain resulting from peripheral nerve lesions is a common medical condition, but current analgesics are often insufficient. The identification of key molecules involved in pathological pain processing is a prerequisite for the development of new analgesic drugs. Hyperexcitability of nociceptive DRG-neurons due to regulation of voltage-gated ion-channels is generally assumed to contribute strongly to neuropathic pain. There is increasing evidence, that T-type Ca2+-currents and in particular the Cav3.2 T-type-channel isoform play an important role in neuropathic pain, but experimental results are contradicting.
Purpose: To clarify the role of T-type Ca2+-channels and in particular the Cav3.2 T-type-channel isoform in neuropathic pain.
Methods: The effect of partial sciatic nerve ligation (PNL) on pain behavior and the properties of T-type-currents in nociceptive DRG-neurons was tested in wild-type and Cav3.2-deficient mice.
Results: In wild-type mice, PNL of the sciatic nerve caused neuropathic pain and an increase of T-type Ca2+-currents in capsaicin-responsive neurons, while capsaicin-unresponsive neurons were unaffected. Pharmacological experiments revealed that this upregulation was due to an increase of a Ni2+-resistant Ca2+-current component, inconsistent with Cav3.2 up-regulation. Moreover, following PNL Cav3.2-deficient mice showed neuropathic pain behavior and an increase of T-Type Ca2+-currents indistinguishable to that of PNL treated wild-type mice.
Conclusion: These data suggest that PNL induces an upregulation of T-Type Ca2+-currents in capsaicin-responsive DRG-neurons mediated by an increase of a Ni2+-insensitive current component (possibly Cav3.1 or Cav3.3). These findings provide relevance for the development of target specific analgesic drugs.

Keywords: T-type Ca2+ channel, nociceptive DRG neuron, neuropathic pain, Cav3.2 knockout mice, partial sciatic nerve ligation

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