Abstract
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.
Conclusion: 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.
Document Type
Article
Publication Date
2-28-2008
Digital Object Identifier (DOI)
https://doi.org/10.1186/1744-8069-4-8
Funding Information
This work was supported by NIH grant NS039041, the Keck Foundation and an anonymous gift.
Repository Citation
Yang, Hong; McNearney, Terry A.; Chu, Rong; Lu, Ying; Ren, Yong; Yeomans, David C.; Wilson, Steven P.; and Westlund, Karin N., "Enkephalin-Encoding Herpes Simplex Virus-1 Decreases Inflammation and Hotplate Sensitivity in a Chronic Pancreatitis Model" (2008). Physiology Faculty Publications. 25.
https://uknowledge.uky.edu/physiology_facpub/25
Notes/Citation Information
Published in Molecular Pain, v. 4, 8, p. 1-21.
© 2008 Yang et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.