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Icilin reduces voltage-gated calcium channel currents in naïve and injured DRG neurons in the rat spinal nerve ligation model.
Brain Res. 2014 Apr 04; 1557:171-9.BR

Abstract

Recently, the transient receptor potential (TRP) channels TRPM8 and TRPA1 have been identified as molecular sensors for cold, and it has been suggested that they play a crucial role in allodynia by modulating voltage-gated calcium channel currents (ICa(V)). The aim of this study was to analyze the modulation of ICa(V) by the TRPM8-agonist icilin in vitro and to investigate the analgesic effect of icilin in a neuropathic pain model in vivo. Whole cell patch-clamp recordings were performed on isolated naïve and injured rat dorsal root ganglia (DRG) neurons, and the analgesic efficacy of icilin applied topically to the paws or intrathecally was tested in rats after spinal nerve ligation (SNL). ICa(V) (depolarization from -80 to 0mV) in naïve DRG neurons was reduced dose dependently (0.002-200µM) by icilin (18-80%). Subtype isolation of calcium channels show a marked reduction of L-type channel currents compared to N-type channel currents. The effects of icilin on ICa(V) were not significantly different in non-injured and SNL-injured DRG neurons. In vivo, neither topical (10-200µM) nor intrathecal application of icilin (0.1nM to 1µM) affected tactile allodynia or thermal hyperalgesia after SNL, but it increases cold allodynia 6h after application. We conclude that the icilin-induced modulation of ICa(V) in DRG neurons is unlikely to mediate analgesic effects or contribute directly to the pathogenesis of cold allodynia in the rat SNL model, but it is a potential mechanism for the analgesic effects of icilin in other pain models.

Authors+Show Affiliations

Department of Neurology, University Hospital Essen, Hufelandstr. 55, 45147 Essen, Germany. Electronic address: tim.hagenacker@uk-essen.de.Department of Neurology, University Hospital Essen, Hufelandstr. 55, 45147 Essen, Germany.Department of Neurology, University Hospital Essen, Hufelandstr. 55, 45147 Essen, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24560602

Citation

Hagenacker, T, et al. "Icilin Reduces Voltage-gated Calcium Channel Currents in Naïve and Injured DRG Neurons in the Rat Spinal Nerve Ligation Model." Brain Research, vol. 1557, 2014, pp. 171-9.
Hagenacker T, Lampe M, Schäfers M. Icilin reduces voltage-gated calcium channel currents in naïve and injured DRG neurons in the rat spinal nerve ligation model. Brain Res. 2014;1557:171-9.
Hagenacker, T., Lampe, M., & Schäfers, M. (2014). Icilin reduces voltage-gated calcium channel currents in naïve and injured DRG neurons in the rat spinal nerve ligation model. Brain Research, 1557, 171-9. https://doi.org/10.1016/j.brainres.2014.02.022
Hagenacker T, Lampe M, Schäfers M. Icilin Reduces Voltage-gated Calcium Channel Currents in Naïve and Injured DRG Neurons in the Rat Spinal Nerve Ligation Model. Brain Res. 2014 Apr 4;1557:171-9. PubMed PMID: 24560602.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Icilin reduces voltage-gated calcium channel currents in naïve and injured DRG neurons in the rat spinal nerve ligation model. AU - Hagenacker,T, AU - Lampe,M, AU - Schäfers,M, Y1 - 2014/02/18/ PY - 2013/10/12/received PY - 2014/02/07/revised PY - 2014/02/11/accepted PY - 2014/2/25/entrez PY - 2014/2/25/pubmed PY - 2014/12/15/medline KW - Cold allodynia KW - Electrophysiology KW - Neuropathic pain KW - Patch clamp KW - Voltage gated calcium channel current SP - 171 EP - 9 JF - Brain research JO - Brain Res VL - 1557 N2 - Recently, the transient receptor potential (TRP) channels TRPM8 and TRPA1 have been identified as molecular sensors for cold, and it has been suggested that they play a crucial role in allodynia by modulating voltage-gated calcium channel currents (ICa(V)). The aim of this study was to analyze the modulation of ICa(V) by the TRPM8-agonist icilin in vitro and to investigate the analgesic effect of icilin in a neuropathic pain model in vivo. Whole cell patch-clamp recordings were performed on isolated naïve and injured rat dorsal root ganglia (DRG) neurons, and the analgesic efficacy of icilin applied topically to the paws or intrathecally was tested in rats after spinal nerve ligation (SNL). ICa(V) (depolarization from -80 to 0mV) in naïve DRG neurons was reduced dose dependently (0.002-200µM) by icilin (18-80%). Subtype isolation of calcium channels show a marked reduction of L-type channel currents compared to N-type channel currents. The effects of icilin on ICa(V) were not significantly different in non-injured and SNL-injured DRG neurons. In vivo, neither topical (10-200µM) nor intrathecal application of icilin (0.1nM to 1µM) affected tactile allodynia or thermal hyperalgesia after SNL, but it increases cold allodynia 6h after application. We conclude that the icilin-induced modulation of ICa(V) in DRG neurons is unlikely to mediate analgesic effects or contribute directly to the pathogenesis of cold allodynia in the rat SNL model, but it is a potential mechanism for the analgesic effects of icilin in other pain models. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/24560602/Icilin_reduces_voltage_gated_calcium_channel_currents_in_naïve_and_injured_DRG_neurons_in_the_rat_spinal_nerve_ligation_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(14)00236-4 DB - PRIME DP - Unbound Medicine ER -