Cargando…
CC chemokine ligand 2 upregulates the current density and expression of TRPV1 channels and Na(v)1.8 sodium channels in dorsal root ganglion neurons
BACKGROUND: Inflammation or nerve injury-induced upregulation and release of chemokine CC chemokine ligand 2 (CCL2) within the dorsal root ganglion (DRG) is believed to enhance the activity of DRG nociceptive neurons and cause hyperalgesia. Transient receptor potential vanilloid receptor 1 (TRPV1) a...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458897/ https://www.ncbi.nlm.nih.gov/pubmed/22870919 http://dx.doi.org/10.1186/1742-2094-9-189 |
_version_ | 1782244727560601600 |
---|---|
author | Kao, Der-Jang Li, Allen H Chen, Jin-Chung Luo, Ro-Sun Chen, Ying-Ling Lu, Juu-Chin Wang, Hung-Li |
author_facet | Kao, Der-Jang Li, Allen H Chen, Jin-Chung Luo, Ro-Sun Chen, Ying-Ling Lu, Juu-Chin Wang, Hung-Li |
author_sort | Kao, Der-Jang |
collection | PubMed |
description | BACKGROUND: Inflammation or nerve injury-induced upregulation and release of chemokine CC chemokine ligand 2 (CCL2) within the dorsal root ganglion (DRG) is believed to enhance the activity of DRG nociceptive neurons and cause hyperalgesia. Transient receptor potential vanilloid receptor 1 (TRPV1) and tetrodotoxin (TTX)-resistant Na(v)1.8 sodium channels play an essential role in regulating the excitability and pain transmission of DRG nociceptive neurons. We therefore tested the hypothesis that CCL2 causes peripheral sensitization of nociceptive DRG neurons by upregulating the function and expression of TRPV1 and Na(v)1.8 channels. METHODS: DRG neuronal culture was prepared from 3-week-old Sprague–Dawley rats and incubated with various concentrations of CCL2 for 24 to 36 hours. Whole-cell voltage-clamp recordings were performed to record TRPV1 agonist capsaicin-evoked inward currents or TTX-insensitive Na(+) currents from control or CCL2-treated small DRG sensory neurons. The CCL2 effect on the mRNA expression of TRPV1 or Na(v)1.8 was measured by real-time quantitative RT-PCR assay. RESULTS: Pretreatment of CCL2 for 24 to 36 hours dose-dependently (EC(50) value = 0.6 ± 0.05 nM) increased the density of capsaicin-induced currents in small putative DRG nociceptive neurons. TRPV1 mRNA expression was greatly upregulated in DRG neurons preincubated with 5 nM CCL2. Pretreating small DRG sensory neurons with CCL2 also increased the density of TTX-resistant Na(+) currents with a concentration-dependent manner (EC(50) value = 0.7 ± 0.06 nM). The Na(v)1.8 mRNA level was significantly increased in DRG neurons pretreated with CCL2. In contrast, CCL2 preincubation failed to affect the mRNA level of TTX-resistant Na(v)1.9. In the presence of the specific phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 or Akt inhibitor IV, CCL2 pretreatment failed to increase the current density of capsaicin-evoked inward currents or TTX-insensitive Na(+) currents and the mRNA level of TRPV1 or Na(v)1.8. CONCLUSIONS: Our results showed that CCL2 increased the function and mRNA level of TRPV1 channels and Na(v)1.8 sodium channels in small DRG sensory neurons via activating the PI3K/Akt signaling pathway. These findings suggest that following tissue inflammation or peripheral nerve injury, upregulation and release of CCL2 within the DRG could facilitate pain transmission mediated by nociceptive DRG neurons and could induce hyperalgesia by upregulating the expression and function of TRPV1 and Na(v)1.8 channels in DRG nociceptive neurons. |
format | Online Article Text |
id | pubmed-3458897 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-34588972012-09-28 CC chemokine ligand 2 upregulates the current density and expression of TRPV1 channels and Na(v)1.8 sodium channels in dorsal root ganglion neurons Kao, Der-Jang Li, Allen H Chen, Jin-Chung Luo, Ro-Sun Chen, Ying-Ling Lu, Juu-Chin Wang, Hung-Li J Neuroinflammation Research BACKGROUND: Inflammation or nerve injury-induced upregulation and release of chemokine CC chemokine ligand 2 (CCL2) within the dorsal root ganglion (DRG) is believed to enhance the activity of DRG nociceptive neurons and cause hyperalgesia. Transient receptor potential vanilloid receptor 1 (TRPV1) and tetrodotoxin (TTX)-resistant Na(v)1.8 sodium channels play an essential role in regulating the excitability and pain transmission of DRG nociceptive neurons. We therefore tested the hypothesis that CCL2 causes peripheral sensitization of nociceptive DRG neurons by upregulating the function and expression of TRPV1 and Na(v)1.8 channels. METHODS: DRG neuronal culture was prepared from 3-week-old Sprague–Dawley rats and incubated with various concentrations of CCL2 for 24 to 36 hours. Whole-cell voltage-clamp recordings were performed to record TRPV1 agonist capsaicin-evoked inward currents or TTX-insensitive Na(+) currents from control or CCL2-treated small DRG sensory neurons. The CCL2 effect on the mRNA expression of TRPV1 or Na(v)1.8 was measured by real-time quantitative RT-PCR assay. RESULTS: Pretreatment of CCL2 for 24 to 36 hours dose-dependently (EC(50) value = 0.6 ± 0.05 nM) increased the density of capsaicin-induced currents in small putative DRG nociceptive neurons. TRPV1 mRNA expression was greatly upregulated in DRG neurons preincubated with 5 nM CCL2. Pretreating small DRG sensory neurons with CCL2 also increased the density of TTX-resistant Na(+) currents with a concentration-dependent manner (EC(50) value = 0.7 ± 0.06 nM). The Na(v)1.8 mRNA level was significantly increased in DRG neurons pretreated with CCL2. In contrast, CCL2 preincubation failed to affect the mRNA level of TTX-resistant Na(v)1.9. In the presence of the specific phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 or Akt inhibitor IV, CCL2 pretreatment failed to increase the current density of capsaicin-evoked inward currents or TTX-insensitive Na(+) currents and the mRNA level of TRPV1 or Na(v)1.8. CONCLUSIONS: Our results showed that CCL2 increased the function and mRNA level of TRPV1 channels and Na(v)1.8 sodium channels in small DRG sensory neurons via activating the PI3K/Akt signaling pathway. These findings suggest that following tissue inflammation or peripheral nerve injury, upregulation and release of CCL2 within the DRG could facilitate pain transmission mediated by nociceptive DRG neurons and could induce hyperalgesia by upregulating the expression and function of TRPV1 and Na(v)1.8 channels in DRG nociceptive neurons. BioMed Central 2012-08-08 /pmc/articles/PMC3458897/ /pubmed/22870919 http://dx.doi.org/10.1186/1742-2094-9-189 Text en Copyright ©2012 Kao et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Kao, Der-Jang Li, Allen H Chen, Jin-Chung Luo, Ro-Sun Chen, Ying-Ling Lu, Juu-Chin Wang, Hung-Li CC chemokine ligand 2 upregulates the current density and expression of TRPV1 channels and Na(v)1.8 sodium channels in dorsal root ganglion neurons |
title | CC chemokine ligand 2 upregulates the current density and expression of TRPV1 channels and Na(v)1.8 sodium channels in dorsal root ganglion neurons |
title_full | CC chemokine ligand 2 upregulates the current density and expression of TRPV1 channels and Na(v)1.8 sodium channels in dorsal root ganglion neurons |
title_fullStr | CC chemokine ligand 2 upregulates the current density and expression of TRPV1 channels and Na(v)1.8 sodium channels in dorsal root ganglion neurons |
title_full_unstemmed | CC chemokine ligand 2 upregulates the current density and expression of TRPV1 channels and Na(v)1.8 sodium channels in dorsal root ganglion neurons |
title_short | CC chemokine ligand 2 upregulates the current density and expression of TRPV1 channels and Na(v)1.8 sodium channels in dorsal root ganglion neurons |
title_sort | cc chemokine ligand 2 upregulates the current density and expression of trpv1 channels and na(v)1.8 sodium channels in dorsal root ganglion neurons |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458897/ https://www.ncbi.nlm.nih.gov/pubmed/22870919 http://dx.doi.org/10.1186/1742-2094-9-189 |
work_keys_str_mv | AT kaoderjang ccchemokineligand2upregulatesthecurrentdensityandexpressionoftrpv1channelsandnav18sodiumchannelsindorsalrootganglionneurons AT liallenh ccchemokineligand2upregulatesthecurrentdensityandexpressionoftrpv1channelsandnav18sodiumchannelsindorsalrootganglionneurons AT chenjinchung ccchemokineligand2upregulatesthecurrentdensityandexpressionoftrpv1channelsandnav18sodiumchannelsindorsalrootganglionneurons AT luorosun ccchemokineligand2upregulatesthecurrentdensityandexpressionoftrpv1channelsandnav18sodiumchannelsindorsalrootganglionneurons AT chenyingling ccchemokineligand2upregulatesthecurrentdensityandexpressionoftrpv1channelsandnav18sodiumchannelsindorsalrootganglionneurons AT lujuuchin ccchemokineligand2upregulatesthecurrentdensityandexpressionoftrpv1channelsandnav18sodiumchannelsindorsalrootganglionneurons AT wanghungli ccchemokineligand2upregulatesthecurrentdensityandexpressionoftrpv1channelsandnav18sodiumchannelsindorsalrootganglionneurons |