HSV-mediated expression of interleukin-4 in dorsal root ganglion neurons reduces neuropathic pain.
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-1beta, PGE2, and phosphorylated-p38 MAP kinase, characteristic of neuropathic pain.


CONCLUSIONS
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.
Hao
Shuanglin
S
Department of Neurology, University of Michigan Health System, 1500 E, Medical Center Drive, Room 1914 TC, Ann Arbor, Michigan 48109-0316, USA. shuhao@umich.edu
Mata
Marina
M
Glorioso
Joseph C
JC
Fink
David J
DJ
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005727:Ganglia, Spinal / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005822:Genetic Vectors / Q000235:genetics; D006930:Hyperalgesia / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D009475:Neurons, Afferent / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D017288:Pain Threshold / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000276:immunology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000235:genetics / Q000276:immunology; D018139:Simplexvirus / Q000235:genetics; D013127:Spinal Nerves / Q000293:injuries / Q000503:physiopathology / Q000601:surgery; D014162:Transfection / Q000379:methods; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D015847:Interleukin-4; D048051:p38 Mitogen-Activated Protein Kinases