Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Molecular Pain
Published in: Molecular Pain 1/2010

Open Access 01-12-2010 | Research

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

Authors: Chao Ma, Jason Rosenzweig, Pu Zhang, David C Johns, Robert H LaMotte

Published in: Molecular Pain | Issue 1/2010

Login to get access

Abstract

Background

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.

Results

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 in vivo 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.

Conclusions

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.
Appendix
Available only for authorised users
Literature
1.
Hu SJ, Xing JL: An experimental model for chronic compression of dorsal root ganglion produced by intervertebral foramen stenosis in the rat. Pain 1998, 77: 15–23. 10.1016/S0304-3959(98)00067-0PubMedCrossRef
2.
Ma C, LaMotte RH: Enhanced excitability of dissociated primary sensory neurons after chronic compression of the dorsal root ganglion in the rat. Pain 2005, 113: 106–112. 10.1016/j.pain.2004.10.001PubMedCrossRef
3.
Ma C, LaMotte RH: Multiple sites for generation of ectopic spontaneous activity in neurons of the chronically compressed dorsal root ganglion. J Neurosci 2007, 27: 14059–14068. 10.1523/JNEUROSCI.3699-07.2007PubMedCentralPubMedCrossRef
4.
Song XJ, Hu SJ, Greenquist KW, Zhang J-M, LaMotte RH: Mechanical and thermal hyperalgesia and ectopic neuronal discharge after chronic compression of dorsal root ganglia. Journal of Neurophysiology 1999, 82: 3347–3358.PubMed
5.
Zhang J-M, Song XJ, LaMotte RH: Enhanced excitability of sensory neurons in rats with cutaneous hyperalgesia produced by chronic compression of the dorsal root ganglion. Journal of Neurophysiology 1999, 82: 3359–3366.PubMed
6.
Johns DC, Marx R, Mains RE, O'Rourke B, Marban E: Inducible genetic suppression of neuronal excitability. J Neurosci 1999, 19: 1691–1697.PubMed
7.
Hoppe UC, Marban E, Johns DC: Adenovirus-mediated inducible gene expression in vivo by a hybrid ecdysone receptor. Mol Ther 2000, 1: 159–164. 10.1006/mthe.1999.0023PubMedCrossRef
8.
Ma C, LaMotte RH, Rosenzweig J, Gehlback PL, Johns DC: Modulation of voltage-gated potassium channels in dorsal root ganglion neurons by an inducible adenoviral vector in vivo. Baltimore, MD: American Society of Gene Therapy 9th Annual Meeting 2006. Abstract No. 902
9.
Ma C, Rosenzweig J, Zhang P, Johns DC, LaMotte RH: 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. Atlanta, GA: Society for Neuroscience Annual Meeting 2006. Program No. 250.5
10.
Ma C, Shu Y, Zheng Z, Chen Y, Yao H, Greenquist KW, White FA, LaMotte RH: Similar electrophysiological changes in axotomized and neighboring intact dorsal root ganglion neurons. J Neurophysiol 2003, 89: 1588–1602. 10.1152/jn.00855.2002PubMedCrossRef
11.
Ma C, Greenquist KW, Lamotte RH: Inflammatory mediators enhance the excitability of chronically compressed dorsal root ganglion neurons. J Neurophysiol 2006, 95: 2098–2107. 10.1152/jn.00748.2005PubMedCrossRef
12.
Song XJ, Vizcarra C, Xu DS, Rupert RL, Wong ZN: Hyperalgesia and neural excitability following injuries to central and peripheral branches of axons and somata of dorsal root ganglion neurons. J Neurophysiol 2003, 89: 2185–2193. 10.1152/jn.00802.2002PubMedCrossRef
13.
Song XJ, Wang ZB, Gan Q, Walters ET: cAMP and cGMP contribute to sensory neuron hyperexcitability and hyperalgesia in rats with dorsal root ganglia compression. J Neurophysiol 2006, 95: 479–492. 10.1152/jn.00503.2005PubMedCrossRef
14.
Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y: Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev 2010, 90: 291–366. 10.1152/physrev.00021.2009PubMedCrossRef
15.
Plaster NM, Tawil R, Tristani-Firouzi M, Canun S, Bendahhou S, Tsunoda A, Donaldson MR, Iannaccone ST, Brunt E, Barohn R, et al.: Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell 2001, 105: 511–519. 10.1016/S0092-8674(01)00342-7PubMedCrossRef
16.
Johns DC, Nuss HB, Chiamvimonvat N, Ramza BM, Marban E, Lawrence JH: Adenovirus-mediated expression of a voltage-gated potassium channel in vitro (rat cardiac myocytes) and in vivo (rat liver). A novel strategy for modifying excitability. J Clin Invest 1995, 96: 1152–1158. 10.1172/JCI118103PubMedCentralPubMedCrossRef
17.
Johns DC, Nuss HB, Marban E: Suppression of neuronal and cardiac transient outward currents by viral gene transfer of dominant-negative Kv4.2 constructs. J Biol Chem 1997, 272: 31598–31603. 10.1074/jbc.272.50.31598PubMedCrossRef
18.
Latremoliere A, Woolf CJ: Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 2009, 10: 895–926. 10.1016/j.jpain.2009.06.012PubMedCentralPubMedCrossRef
19.
Xie W, Strong JA, Meij JT, Zhang JM, Yu L: Neuropathic pain: early spontaneous afferent activity is the trigger. Pain 2005, 116: 243–256. 10.1016/j.pain.2005.04.017PubMedCentralPubMedCrossRef
20.
Ma C, Donnelly DF, LaMotte RH: In vivo visualization and functional characterization of primary somatic neurons. J Neurosci Methods 2010, 191: 60–65. 10.1016/j.jneumeth.2010.06.010PubMedCentralPubMedCrossRef
21.
Metadata
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
Authors
Chao Ma
Jason Rosenzweig
Pu Zhang
David C Johns
Robert H LaMotte
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Pain / Issue 1/2010
Electronic ISSN: 1744-8069
DOI
https://doi.org/10.1186/1744-8069-6-65

Other articles of this Issue 1/2010

Molecular Pain 1/2010 Go to the issue

Research

Ablation of rat TRPV1-expressing Adelta/C-fibers with resiniferatoxin: analysis of withdrawal behaviors, recovery of function and molecular correlates

Research

Familial hemiplegic migraine CaV2.1 channel mutation R192Q enhances ATP-gated P2X3 receptor activity of mouse sensory ganglion neurons mediating trigeminal pain

Research

Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain

Research

In vivo whole-cell patch-clamp recording of sensory synaptic responses of cingulate pyramidal neurons to noxious mechanical stimuli in adult mice

Research

Hydrogen sulphide induces μ opioid receptor-dependent analgesia in a rodent model of visceral pain

Research

Expression of leukotriene receptors in the rat dorsal root ganglion and the effects on pain behaviors