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

被引：3

作者：

Jeub, Monika ^{[1
,2
]}

Taha, Omneya ^{[1
,2
]}

Opitz, Thoralf ^{[2
]}

Racz, Ildiko ^{[3
,4
]}

Pitsch, Julika ^{[5
]}

Becker, Albert ^{[5
]}

Beck, Heinz ^{[2
]}

机构：

[1] Univ Bonn, Dept Neurol, Med Ctr, Bonn, Germany

[2] Univ Bonn, Dept Epileptol, Med Ctr, Sigmund Freud Str 25, D-53105 Bonn, Germany

[3] Univ Bonn, Inst Mol Psychiat, Med Ctr, Bonn, Germany

[4] Univ Bonn, Dept Neurodegenerat Dis & Gerontopsychiat, Med Ctr, Bonn, Germany

[5] Univ Bonn, Dept Neuropathol, Med Ctr, Bonn, Germany

来源：

JOURNAL OF PAIN RESEARCH | 2019年 / 12卷

关键词：

T-type Cat(2+) channel; nociceptive DRG neuron; neuropathic pain; Ca(v)3.2 knockout mice; partial sciatic nerve ligation; SENSORY NEURONS; NEUROPATHIC PAIN; CALCIUM CURRENT; CHANNELS; CA(V)3.2; INJURY; RATS; HYPERALGESIA; GENE; DRG;

D O I：

10.2147/JPR.S138708

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Neuropathic pain resulting from peripheral nerve lesions is a common medical condition, but current analgesics arc 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 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 Ca2+-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 ofT-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-typc 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 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 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 Ca(v)3.1 or Ca(v)3.3). These findings provide relevance for the development of target specific analgesic drugs.

引用

页码：635 / 647

页数：13