Relief of pain induced by varicella-zoster virus in a rat model of post-herpetic neuralgia using a herpes simplex virus vector expressing enkephalin
Identifieur interne : 002030 ( Ncbi/Checkpoint ); précédent : 002029; suivant : 002031Relief of pain induced by varicella-zoster virus in a rat model of post-herpetic neuralgia using a herpes simplex virus vector expressing enkephalin
Auteurs : J-Mg Guedon [États-Unis] ; M. Zhang [États-Unis] ; Jc Glorioso [États-Unis] ; Wf Goins [États-Unis] ; Pr Kinchington [États-Unis]Source :
- Gene therapy [ 0969-7128 ] ; 2014.
Descripteurs français
- KwdFr :
- Algie post-zona (), Animaux, Enképhalines (génétique), Enképhalines (métabolisme), Humains, Lignée cellulaire tumorale, Modèles animaux de maladie humaine, Moelle spinale (métabolisme), Mâle, Pied (virologie), Pseudokystes mucoïdes juxta-articulaires (métabolisme), Rat Sprague-Dawley, Rats, Simplexvirus (génétique), Thérapie génétique, Vecteurs génétiques (administration et posologie).
- MESH :
- administration et posologie : Vecteurs génétiques.
- génétique : Enképhalines, Simplexvirus.
- métabolisme : Enképhalines, Moelle spinale, Pseudokystes mucoïdes juxta-articulaires.
- virologie : Pied.
- Algie post-zona, Animaux, Humains, Lignée cellulaire tumorale, Modèles animaux de maladie humaine, Mâle, Rat Sprague-Dawley, Rats, Thérapie génétique.
English descriptors
- KwdEn :
- Animals, Cell Line, Tumor, Disease Models, Animal, Enkephalins (genetics), Enkephalins (metabolism), Foot (virology), Ganglion Cysts (metabolism), Genetic Therapy, Genetic Vectors (administration & dosage), Humans, Male, Neuralgia, Postherpetic (prevention & control), Neuralgia, Postherpetic (therapy), Rats, Rats, Sprague-Dawley, Simplexvirus (genetics), Spinal Cord (metabolism).
- MESH :
- chemical , genetics : Enkephalins.
- chemical , metabolism : Enkephalins.
- administration & dosage : Genetic Vectors.
- genetics : Simplexvirus.
- metabolism : Ganglion Cysts, Spinal Cord.
- prevention & control : Neuralgia, Postherpetic.
- therapy : Neuralgia, Postherpetic.
- virology : Foot.
- Animals, Cell Line, Tumor, Disease Models, Animal, Genetic Therapy, Humans, Male, Rats, Rats, Sprague-Dawley.
Abstract
Acute and chronic pain (post-herpetic neuralgia or PHN) are encountered in patients with herpes zoster that is caused by reactivation of varicella-zoster virus (VZV) from a state of neuronal latency. PHN is often refractory to current treatments, and additional strategies for pain relief are needed. Here we exploited a rat footpad model of PHN to show that herpes simplex virus (HSV) vector-mediated gene delivery of human preproenkephalin (vHPPE) effectively reduced chronic VZV-induced nocifensive indicators of pain. VZV inoculated at the footpad induced prolonged mechanical allodynia and thermal hyperalgesia that did not develop in controls or with ultraviolet light-inactivated VZV. Subsequent footpad administration of vHPPE relieved VZV-induced pain behaviors in a dose-dependent manner for extended periods, and prophylactic vector administration prevented VZV-induced pain from developing. Short-term pain relief following low-dose vHPPE administration could be effectively prolonged by vector re-administration. HPPE transcripts were increased three- to fivefold in ipsilateral ganglia, but not in the contralateral dorsal root ganglia. VZV hypersensitivity and its relief by vHPPE were not affected by peripheral delivery of opioid receptor agonist or antagonist, suggesting that the efficacy was mediated at the ganglion and/or spinal cord level. These results support further development of ganglionic expression of enkephalin as a novel treatment for the pain associated with Zoster.
Url:
DOI: 10.1038/gt.2014.43
PubMed: 24830437
PubMed Central: 4324603
Affiliations:
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<term>Cell Line, Tumor</term>
<term>Disease Models, Animal</term>
<term>Enkephalins (genetics)</term>
<term>Enkephalins (metabolism)</term>
<term>Foot (virology)</term>
<term>Ganglion Cysts (metabolism)</term>
<term>Genetic Therapy</term>
<term>Genetic Vectors (administration & dosage)</term>
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<term>Neuralgia, Postherpetic (prevention & control)</term>
<term>Neuralgia, Postherpetic (therapy)</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Algie post-zona ()</term>
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<term>Enképhalines (génétique)</term>
<term>Enképhalines (métabolisme)</term>
<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
<term>Modèles animaux de maladie humaine</term>
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<term>Mâle</term>
<term>Pied (virologie)</term>
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<term>Rat Sprague-Dawley</term>
<term>Rats</term>
<term>Simplexvirus (génétique)</term>
<term>Thérapie génétique</term>
<term>Vecteurs génétiques (administration et posologie)</term>
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<keywords scheme="MESH" qualifier="administration & dosage" xml:lang="en"><term>Genetic Vectors</term>
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<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Vecteurs génétiques</term>
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<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Enképhalines</term>
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<term>Pseudokystes mucoïdes juxta-articulaires</term>
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<front><div type="abstract" xml:lang="en"><p id="P1">Acute and chronic pain (post-herpetic neuralgia or PHN) are encountered in patients with herpes zoster that is caused by reactivation of varicella-zoster virus (VZV) from a state of neuronal latency. PHN is often refractory to current treatments, and additional strategies for pain relief are needed. Here we exploited a rat footpad model of PHN to show that herpes simplex virus (HSV) vector-mediated gene delivery of human preproenkephalin (vHPPE) effectively reduced chronic VZV-induced nocifensive indicators of pain. VZV inoculated at the footpad induced prolonged mechanical allodynia and thermal hyperalgesia that did not develop in controls or with ultraviolet light-inactivated VZV. Subsequent footpad administration of vHPPE relieved VZV-induced pain behaviors in a dose-dependent manner for extended periods, and prophylactic vector administration prevented VZV-induced pain from developing. Short-term pain relief following low-dose vHPPE administration could be effectively prolonged by vector re-administration. HPPE transcripts were increased three- to fivefold in ipsilateral ganglia, but not in the contralateral dorsal root ganglia. VZV hypersensitivity and its relief by vHPPE were not affected by peripheral delivery of opioid receptor agonist or antagonist, suggesting that the efficacy was mediated at the ganglion and/or spinal cord level. These results support further development of ganglionic expression of enkephalin as a novel treatment for the pain associated with Zoster.</p>
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