HSV-mediated expression of interleukin-4 in dorsal root ganglion neurons reduces neuropathic pain

Shuanglin Hao, Marina Mata, Joseph C. Glorioso, David J. Fink

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Background: To examine the role of inflammatory mediators in neuropathic pain, we used a replication-defective genomic herpes simplex virus (HSV)-based vector containing the coding sequence for the anti-inflammatory peptide interleukin (IL)-4 under the transcriptional control of the HSV ICP4 immediate early promoter, vector S4IL4, to express IL-4 in dorsal root ganglion (DRG) neurons in vivo. Results: Subcutaneous inoculation of S4IL4 in the foot transduced lumbar DRG to produce IL-4. Transgene-mediated expression of IL-4 did not alter thermal latency or tactile threshold in normal animals, but inoculation of S4IL4 1 week after spinal nerve ligation (SNL) reduced mechanical allodynia and reversed thermal hyperalgesia resulting from SNL. Inoculation of S4IL4 1 week before SNL delayed the development of thermal hyperalgesia and tactile allodynia, but did not prevent the ultimate development of these manifestations of neuropathic pain. S4IL4 inoculation suppressed non-noxious-induced expression of c-Fos immunoreactivity in dorsal horn of spinal cord and reversed the upregulation of spinal IL-1β, PGE2, and phosphorylated-p38 MAP kinase, characteristic of neuropathic pain. Conclusion: HSV-mediated expression of IL-4 effectively reduces the behavioral manifestations of neuropathic pain, and reverses some of the biochemical and histologic correlates of neuropathic pain at the spinal level.

Original languageEnglish
Article number6
JournalMolecular Pain
Volume2
DOIs
StatePublished - Feb 17 2006
Externally publishedYes

Fingerprint

Hyperalgesia
Spinal Ganglia
Neuralgia
Simplexvirus
Interleukin-4
Spinal Nerves
Neurons
Ligation
Touch
p38 Mitogen-Activated Protein Kinases
Transgenes
Interleukin-1
Dinoprostone
Foot
Anti-Inflammatory Agents
Up-Regulation
Hot Temperature
Peptides

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Molecular Medicine
  • Cellular and Molecular Neuroscience

Cite this

HSV-mediated expression of interleukin-4 in dorsal root ganglion neurons reduces neuropathic pain. / Hao, Shuanglin; Mata, Marina; Glorioso, Joseph C.; Fink, David J.

In: Molecular Pain, Vol. 2, 6, 17.02.2006.

Research output: Contribution to journalArticle

@article{8550110d61a74285a24d8ac69ca0c95a,
title = "HSV-mediated expression of interleukin-4 in dorsal root ganglion neurons reduces neuropathic pain",
abstract = "Background: To examine the role of inflammatory mediators in neuropathic pain, we used a replication-defective genomic herpes simplex virus (HSV)-based vector containing the coding sequence for the anti-inflammatory peptide interleukin (IL)-4 under the transcriptional control of the HSV ICP4 immediate early promoter, vector S4IL4, to express IL-4 in dorsal root ganglion (DRG) neurons in vivo. Results: Subcutaneous inoculation of S4IL4 in the foot transduced lumbar DRG to produce IL-4. Transgene-mediated expression of IL-4 did not alter thermal latency or tactile threshold in normal animals, but inoculation of S4IL4 1 week after spinal nerve ligation (SNL) reduced mechanical allodynia and reversed thermal hyperalgesia resulting from SNL. Inoculation of S4IL4 1 week before SNL delayed the development of thermal hyperalgesia and tactile allodynia, but did not prevent the ultimate development of these manifestations of neuropathic pain. S4IL4 inoculation suppressed non-noxious-induced expression of c-Fos immunoreactivity in dorsal horn of spinal cord and reversed the upregulation of spinal IL-1β, PGE2, and phosphorylated-p38 MAP kinase, characteristic of neuropathic pain. Conclusion: HSV-mediated expression of IL-4 effectively reduces the behavioral manifestations of neuropathic pain, and reverses some of the biochemical and histologic correlates of neuropathic pain at the spinal level.",
author = "Shuanglin Hao and Marina Mata and Glorioso, {Joseph C.} and Fink, {David J.}",
year = "2006",
month = "2",
day = "17",
doi = "10.1186/1744-8069-2-6",
language = "English",
volume = "2",
journal = "Molecular Pain",
issn = "1744-8069",
publisher = "BioMed Central",

}

TY - JOUR

T1 - HSV-mediated expression of interleukin-4 in dorsal root ganglion neurons reduces neuropathic pain

AU - Hao, Shuanglin

AU - Mata, Marina

AU - Glorioso, Joseph C.

AU - Fink, David J.

PY - 2006/2/17

Y1 - 2006/2/17

N2 - Background: To examine the role of inflammatory mediators in neuropathic pain, we used a replication-defective genomic herpes simplex virus (HSV)-based vector containing the coding sequence for the anti-inflammatory peptide interleukin (IL)-4 under the transcriptional control of the HSV ICP4 immediate early promoter, vector S4IL4, to express IL-4 in dorsal root ganglion (DRG) neurons in vivo. Results: Subcutaneous inoculation of S4IL4 in the foot transduced lumbar DRG to produce IL-4. Transgene-mediated expression of IL-4 did not alter thermal latency or tactile threshold in normal animals, but inoculation of S4IL4 1 week after spinal nerve ligation (SNL) reduced mechanical allodynia and reversed thermal hyperalgesia resulting from SNL. Inoculation of S4IL4 1 week before SNL delayed the development of thermal hyperalgesia and tactile allodynia, but did not prevent the ultimate development of these manifestations of neuropathic pain. S4IL4 inoculation suppressed non-noxious-induced expression of c-Fos immunoreactivity in dorsal horn of spinal cord and reversed the upregulation of spinal IL-1β, PGE2, and phosphorylated-p38 MAP kinase, characteristic of neuropathic pain. Conclusion: HSV-mediated expression of IL-4 effectively reduces the behavioral manifestations of neuropathic pain, and reverses some of the biochemical and histologic correlates of neuropathic pain at the spinal level.

AB - Background: To examine the role of inflammatory mediators in neuropathic pain, we used a replication-defective genomic herpes simplex virus (HSV)-based vector containing the coding sequence for the anti-inflammatory peptide interleukin (IL)-4 under the transcriptional control of the HSV ICP4 immediate early promoter, vector S4IL4, to express IL-4 in dorsal root ganglion (DRG) neurons in vivo. Results: Subcutaneous inoculation of S4IL4 in the foot transduced lumbar DRG to produce IL-4. Transgene-mediated expression of IL-4 did not alter thermal latency or tactile threshold in normal animals, but inoculation of S4IL4 1 week after spinal nerve ligation (SNL) reduced mechanical allodynia and reversed thermal hyperalgesia resulting from SNL. Inoculation of S4IL4 1 week before SNL delayed the development of thermal hyperalgesia and tactile allodynia, but did not prevent the ultimate development of these manifestations of neuropathic pain. S4IL4 inoculation suppressed non-noxious-induced expression of c-Fos immunoreactivity in dorsal horn of spinal cord and reversed the upregulation of spinal IL-1β, PGE2, and phosphorylated-p38 MAP kinase, characteristic of neuropathic pain. Conclusion: HSV-mediated expression of IL-4 effectively reduces the behavioral manifestations of neuropathic pain, and reverses some of the biochemical and histologic correlates of neuropathic pain at the spinal level.

UR - http://www.scopus.com/inward/record.url?scp=33646409615&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646409615&partnerID=8YFLogxK

U2 - 10.1186/1744-8069-2-6

DO - 10.1186/1744-8069-2-6

M3 - Article

C2 - 16503976

AN - SCOPUS:33646409615

VL - 2

JO - Molecular Pain

JF - Molecular Pain

SN - 1744-8069

M1 - 6

ER -