Partial sciatic nerve ligation leads to an upregulation of Ni 2+ -resistant T-type Ca 2+ currents in capsaicin-responsive nociceptive dorsal root ganglion neurons

Monika Jeub, Omneya Taha, Thoralf Opitz, Ildiko Racz, Julika Pitsch, Albert Becker, Heinz Beck

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 Ca 2+ -currents and in particular the Ca v 3.2 T-type-channel isoform play an important role in neuropathic pain, but experimental results are contradicting. Purpose: To clarify the role of T-type Ca 2+ -channels and in particular the Ca v 3.2 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 Ca v 3.2-deficient mice. Results: In wild-type mice, PNL of the sciatic nerve caused neuropathic pain and an increase of T-type Ca 2+ -currents in capsaicin-responsive neurons, while capsaicin-unresponsive neurons were unaffected. Pharmacological experiments revealed that this upregulation was due to an increase of a Ni 2+ -resistant Ca 2+ -current component, inconsistent with Ca v 3.2 up-regulation. Moreover, following PNL Ca v 3.2-deficient mice showed neuropathic pain behavior and an increase of T-Type Ca 2+ -currents indistinguishable to that of PNL treated wild-type mice. Conclusion: These data suggest that PNL induces an upregulation of T-Type Ca 2+ -currents in capsaicin-responsive DRG-neurons mediated by an increase of a Ni 2+ -insensitive current component (possibly Ca v 3.1 or Ca v 3.3). These findings provide relevance for the development of target specific analgesic drugs.
Original languageEnglish
Pages (from-to)635-647
JournalJournal of Pain Research
Volume12
DOIs
Publication statusPublished - 1 Jan 2019
Externally publishedYes

Cite this