[Periaqueductal gray administration of HSV-I amplicon vector-mediated HPPE gene therapy of nocicepion in rats with formalin-induced pain].
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.


CONCLUSIONS
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.
Zou
Wang-Yuan
WY
Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, China.
Yang
Yong
Y
Guo
Qu-Lian
QL
D000818:Animals; D004745:Enkephalins / Q000235:genetics*; D005557:Formaldehyde; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D008297:Male; D008845:Microinjections; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000139:chemically induced; D059408:Pain Management; D010487:Periaqueductal Gray; D011498:Protein Precursors / Q000235:genetics*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D004745:Enkephalins; D011498:Protein Precursors; D005557:Formaldehyde; C033660:preproenkephalin