Periaqueductal gray administration of HSV-I amplicon vector-mediated HPPE gene therapy of nocicepion in rats with formalin-induced pain.
- Author:
Wang-Yuan ZOU
1
;
Yong YANG
;
Qu-Lian GUO
Author Information
1. Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Enkephalins;
genetics;
Formaldehyde;
Gene Transfer Techniques;
Genetic Therapy;
Genetic Vectors;
administration & dosage;
Herpesvirus 1, Human;
genetics;
Male;
Microinjections;
Nociceptors;
drug effects;
Pain;
chemically induced;
Pain Management;
Periaqueductal Gray;
Protein Precursors;
genetics;
Random Allocation;
Rats;
Rats, Sprague-Dawley
- From:
Journal of Central South University(Medical Sciences)
2008;33(6):481-487
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the antinociceptive effect of periaqueductal gray (PAG) administration of herpes simplex virus type-1(HSV-I) amplicon vector-mediated human preproenkephalin gene (HPPE).
METHODS:Sprague-Dawley rats weighting 260 to approximately 320 g were randomly divided into pHSVIRES-HPPE-LacZ (SHPZ) group, pHSVIRES-LacZ (SHZ) group, and saline (NS) group which included 3 d,1 week,2 week,3 week,4 week,5 week, and 6 week groups (n=51). The rats were anesthetized with intraperitoneal chloral hydrate (300 to approximately 350) mg/kg. Rats were PAG delivered with recombinant HSV-I amplicon vector SHPZ, SHZ or NS. One week after PAG administration 9 rats in each group were sacrificed and lumber segment of the spinal cord was removed for determination of expression of LacZ by X-gal staining and HPPE mRNA expression by reverse transcription-polymerase chain reaction and L-enkephalin content by radioimmunoassay in PAG. Formalin 50 microL (5%) was injected into the left hindpaw, and pain intensity scoring (PIS) was used to assess the antinociceptive effect.
RESULTS:After in vivo transferring, neurocyte demonstrated strong positive signals with X-gal immunohistochemical staining. The expression of HPPE mRNA was detected in PAG after administration of SHPZ. PAG delivery of SHPZ showed antinociceptive effect on formalin-induced pain for 6 weeks compared with SHZ group.
CONCLUSION:This amplicon virus can transfer HPPE into rat PAG neural cells and make it express efficiently. PAG administration of SHPZ can produce significant analgesic effect on formalin-induced pain in rats for 5 weeks.