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.