Abstract
To investigate the antinociceptive effect of intrathecal (IT) injection of Herpes simplex virus type I (HSV-1) amplicon vector-mediated HPPE on chronic neuropathic pain. 45 Sprague-Dawley rats underwent chronic constriction. Injury (CCI) of unilateral sciatic nerve and then were randomly divided into 3 equal groups: CCI + normal saline group, undergoing insertion of microspinal catheter into the subarachnoid space at the lumber region and intrathecal delivery of NS, CCI + pHSVIRES-LacZ (SHPZ) group undergoing intrathecal delivery of and recombinant HSV-I amplicon vector pHSVIRES-HPPE-LacZ containing human pre-proenkephalin (HPPE) gene, and CCI + blank vector (SHZ) group receiving pHSV-HPPE-LacZ. Another 15 rats underwent sham operation to be used as control group. One week after IT administration 9 rats from each group were killed with their lumber segments of spinal cord removed to detect the expression of LacZ by X-gal staining, HPPE mRNA expression by RT-PCR, and L-enkephalin (L-EK) content by radioimmunoassay. Paw mechanical withdrawal threshold (PMWT) and paw withdrawal thermal latency (PWTL) were measured before CCI (baseline) and 3 days after CCI and then once a week for 5 weeks after IT administration. After IT administration of SHPZ expression of HPPE mRNA was detected in the spinal cord. One week after the IT injection the L-EK level of the SHPZ group was (748 +/- 185 ng/L), significantly higher than those of the Sham operation, NS, and SHZ groups [(452 +/- 89), (453 +/- 92), and (451 +/- 99) ng/L respectively, all P < 0.05]. The PWMT and PWTL levels of the SHPZ group were significantly increased since 1 week after the IT administration in comparison with the baseline values and those of the other 3 groups (all P < 0.05), and these effects peaked in the third week and then lasted to the fifth week. However, the threshold to mechanical and thermal stimuli was not affected by intrathecal delivery of vehicle or SHZ compared with the threshold before intrathecal delivery. Intrathecal administration SHPZ can produce significant analgesic effects on chronic neuropathic pain in rats.
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