Enkephalin-encoding herpes simplex virus-1 decreases inflammation and hotplate sensitivity in a chronic pancreatitis model.
BACKGROUND
A chronic pancreatitis model was developed in young male Lewis rats fed a high-fat and alcohol liquid diet beginning at three weeks. The model was used to assess time course and efficacy of a replication defective herpes simplex virus type 1 vector construct delivering human cDNA encoding preproenkephalin (HSV-ENK).


RESULTS
Most surprising was the relative lack of inflammation and tissue disruption after HSV-ENK treatment compared to the histopathology consistent with pancreatitis (inflammatory cell infiltration, edema, acinar cell hypertrophy, fibrosis) present as a result of the high-fat and alcohol diet in controls. The HSV-ENK vector delivered to the pancreatic surface at week 3 reversed pancreatitis-associated hotplate hypersensitive responses for 4-6 weeks, while control virus encoding beta-galactosidase cDNA (HSV-beta-gal) had no effect. Increased Fos expression seen bilaterally in pain processing regions in control animals with pancreatitis was absent in HSV-ENK-treated animals. Increased met-enkephalin staining was evident in pancreas and lower thoracic spinal cord laminae I-II in the HSV-ENK-treated rats.


CONCLUSIONS
Thus, clear evidence is provided that site specific HSV-mediated transgene delivery of human cDNA encoding preproenkephalin ameliorates pancreatic inflammation and significantly reduces hypersensitive hotplate responses for an extended time consistent with HSV mediated overexpression, without tolerance or evidence of other opiate related side effects.
Yang
Hong
H
Dept of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX, USA. hoyang@utmb.edu
McNearney
Terry A
TA
Chu
Rong
R
Lu
Ying
Y
Ren
Yong
Y
Yeomans
David C
DC
Wilson
Steven P
SP
Westlund
Karin N
KN
D000818:Animals; D001522:Behavior, Animal; D018076:DNA, Complementary / Q000378:metabolism; D004745:Enkephalins / Q000235:genetics*; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000235:genetics*; D007249:Inflammation / Q000378:metabolism / Q000628:therapy; D008297:Male; D023421:Models, Animal; D050500:Pancreatitis, Chronic / Q000628:therapy*; D011498:Protein Precursors / Q000235:genetics*; D051381:Rats; D011917:Rats, Inbred Lew; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D013997:Time Factors
D018076:DNA, Complementary; D004745:Enkephalins; D011498:Protein Precursors; D017450:Receptors, Opioid, mu; C033660:preproenkephalin