Expression of inwardly rectifying potassium channels by an inducible adenoviral vector reduced the neuronal hyperexcitability and hyperalgesia produced by chronic compression of the spinal ganglion
<p>Abstract</p> <p>Background</p> <p>A chronic compressed dorsal root ganglion (CCD) in rat produces pain behavior and an enhanced excitability of neurons within the compressed ganglion. Kir2.1 is an inwardly rectifying potassium channel that acts to stabilize the resti...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2010-10-01
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| Series: | Molecular Pain |
| Online Access: | http://www.molecularpain.com/content/6/1/65 |
| _version_ | 1811244906036854784 |
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| author | Johns David C Zhang Pu Rosenzweig Jason Ma Chao LaMotte Robert H |
| author_facet | Johns David C Zhang Pu Rosenzweig Jason Ma Chao LaMotte Robert H |
| author_sort | Johns David C |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>A chronic compressed dorsal root ganglion (CCD) in rat produces pain behavior and an enhanced excitability of neurons within the compressed ganglion. Kir2.1 is an inwardly rectifying potassium channel that acts to stabilize the resting potential of certain cell types. We hypothesized that an inducible expression of Kir2.1 channels in CCD neurons might suppress neuronal excitability in the dorsal root ganglion (DRG) and reduce the associated pain behavior.</p> <p>Results</p> <p>We delivered, by microinjection into the fourth lumbar (L4) DRG, an adenoviral vector containing a reporter gene encoding the enhanced green fluorescent protein (GFP) and a Kir2.1 channel (AdKir). At the same time the ganglion was compressed by implantation of a rod through the intervertebral foramen (CCD). The <it>in vivo </it>expression of the transferred gene was controlled by an ecdysone analog via an ecdysone-inducible promoter in the viral vector. In comparison with the effects of vehicle or a control vector containing only the GFP gene, AdKir significantly reduced the neuronal hyperexcitability after CCD. Electrophysiological recordings, in vivo, from nociceptive and non-nociceptive DRG neurons expressing the virally produced Kir2.1 channels revealed a hyperpolarized resting membrane potential, an increased rheobase, and lack of spontaneous activity. Inducing the Kir2.1 gene at the beginning of CCD surgery partially prevented the development of mechanical hyperalgesia. However, a delayed induction of the Kir2.1 gene (3 days after CCD surgery) produced no significant effect on the pain behavior.</p> <p>Conclusions</p> <p>We found that an inducible expression of Kir2.1 channels in chronically compressed DRG neurons can effectively suppress the neuronal excitability and, if induced at the beginning of CCD injury, prevent the development of hyperalgesia. We hypothesize that a higher level of neuronal hyperexcitability in the DRG is required to initiate than to maintain the hyperalgesia and that the hyperexcitability contributing to neuropathic pain is best inhibited as soon as possible after injury.</p> |
| first_indexed | 2024-04-12T14:32:48Z |
| format | Article |
| id | doaj.art-d1d9538f8f884735ada19c0e37831832 |
| institution | Directory Open Access Journal |
| issn | 1744-8069 |
| language | English |
| last_indexed | 2024-04-12T14:32:48Z |
| publishDate | 2010-10-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Pain |
| spelling | doaj.art-d1d9538f8f884735ada19c0e378318322022-12-22T03:29:13ZengSAGE PublishingMolecular Pain1744-80692010-10-01616510.1186/1744-8069-6-65Expression of inwardly rectifying potassium channels by an inducible adenoviral vector reduced the neuronal hyperexcitability and hyperalgesia produced by chronic compression of the spinal ganglionJohns David CZhang PuRosenzweig JasonMa ChaoLaMotte Robert H<p>Abstract</p> <p>Background</p> <p>A chronic compressed dorsal root ganglion (CCD) in rat produces pain behavior and an enhanced excitability of neurons within the compressed ganglion. Kir2.1 is an inwardly rectifying potassium channel that acts to stabilize the resting potential of certain cell types. We hypothesized that an inducible expression of Kir2.1 channels in CCD neurons might suppress neuronal excitability in the dorsal root ganglion (DRG) and reduce the associated pain behavior.</p> <p>Results</p> <p>We delivered, by microinjection into the fourth lumbar (L4) DRG, an adenoviral vector containing a reporter gene encoding the enhanced green fluorescent protein (GFP) and a Kir2.1 channel (AdKir). At the same time the ganglion was compressed by implantation of a rod through the intervertebral foramen (CCD). The <it>in vivo </it>expression of the transferred gene was controlled by an ecdysone analog via an ecdysone-inducible promoter in the viral vector. In comparison with the effects of vehicle or a control vector containing only the GFP gene, AdKir significantly reduced the neuronal hyperexcitability after CCD. Electrophysiological recordings, in vivo, from nociceptive and non-nociceptive DRG neurons expressing the virally produced Kir2.1 channels revealed a hyperpolarized resting membrane potential, an increased rheobase, and lack of spontaneous activity. Inducing the Kir2.1 gene at the beginning of CCD surgery partially prevented the development of mechanical hyperalgesia. However, a delayed induction of the Kir2.1 gene (3 days after CCD surgery) produced no significant effect on the pain behavior.</p> <p>Conclusions</p> <p>We found that an inducible expression of Kir2.1 channels in chronically compressed DRG neurons can effectively suppress the neuronal excitability and, if induced at the beginning of CCD injury, prevent the development of hyperalgesia. We hypothesize that a higher level of neuronal hyperexcitability in the DRG is required to initiate than to maintain the hyperalgesia and that the hyperexcitability contributing to neuropathic pain is best inhibited as soon as possible after injury.</p>http://www.molecularpain.com/content/6/1/65 |
| spellingShingle | Johns David C Zhang Pu Rosenzweig Jason Ma Chao LaMotte Robert H Expression of inwardly rectifying potassium channels by an inducible adenoviral vector reduced the neuronal hyperexcitability and hyperalgesia produced by chronic compression of the spinal ganglion Molecular Pain |
| title | Expression of inwardly rectifying potassium channels by an inducible adenoviral vector reduced the neuronal hyperexcitability and hyperalgesia produced by chronic compression of the spinal ganglion |
| title_full | Expression of inwardly rectifying potassium channels by an inducible adenoviral vector reduced the neuronal hyperexcitability and hyperalgesia produced by chronic compression of the spinal ganglion |
| title_fullStr | Expression of inwardly rectifying potassium channels by an inducible adenoviral vector reduced the neuronal hyperexcitability and hyperalgesia produced by chronic compression of the spinal ganglion |
| title_full_unstemmed | Expression of inwardly rectifying potassium channels by an inducible adenoviral vector reduced the neuronal hyperexcitability and hyperalgesia produced by chronic compression of the spinal ganglion |
| title_short | Expression of inwardly rectifying potassium channels by an inducible adenoviral vector reduced the neuronal hyperexcitability and hyperalgesia produced by chronic compression of the spinal ganglion |
| title_sort | expression of inwardly rectifying potassium channels by an inducible adenoviral vector reduced the neuronal hyperexcitability and hyperalgesia produced by chronic compression of the spinal ganglion |
| url | http://www.molecularpain.com/content/6/1/65 |
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