Analgesic effect of intrathecal transplant of immortalized rat astrocyte strain genetically modified by human preproenkephalin gene on rat chronic neuropathic pain

Objective: To observe the analgesic effect of intrathecal transplant of immortalized rat astrocyte genetically modified by human preproenkephalin gene(IAST/hPPE) on chronic neuropathic pain. Methods: 40 adult male Sprague-Dawley rats were randomly divided into four groups, 10 rats for each group. Naive group, SNI group, SNI + IAST group and SNI + IAST/hPPE group. The immortalized rat astrocyte (IAST) or IAST/hPPE co-incubated with bromodeoxyuridine (BrdU) in vitro were transplanted in the lumbar 4 to 6 subarachnoid space near the spinal cord 1 week after right side spared nerve injury (SNI). All animals were tested for bilateral 50% hindpaw withdrawal threshold(PWT) to a graded series of Von Frey hairs stimulation once a week from one week before SNI to six weeks after transplant, the difference value for right 50% PWT minus left 50% PWT was calculated and the effect of intraperitoneal naloxone on the analgesic efficacies was also observed. The content of L-EK in the spinal cord of L_4-6 and was determined using immunohistochemistry and radioimmunoassay, and the expression of BrdU in grafts was determined using immunohistochemistry. Results: Allodynia-like behaviour after 1 week following SNI was observed. As compared with Naive group, the difference value for the right 50% PWT minus left 50% PWT in the other three groups was higher significantly (P < 0.01). The tactile allodynia induced by SNI was significantly alleviated during the 1 to 6 week period after transplantation of IAST/hPPE cells, but transplants of IAST cells had no effect on the allodynia-like behaviour. The difference value for the right 50% PWT minus left 50% PWT in SNI + IAST/hPPE group was lower significantly than that in the SNI and SNI + IAST group (P < 0.01), but there was no significant difference between SNI and SNI + IAST group (P > 0.05). The efficacies were reversed by intraperitoneal naloxone in SNI + IAST/hPPE group. The content of L-EK in the lumbar spinal cord in IAST/hPPE group (108.1 pg/mg ± 12.5 pg/mg) was significantly higher than that in other three groups (P < 0.01), but there was no significant difference between SNI and SNI + IAST group. Furthermore, The grafts in the surface of dorsal horn were still stained positively for BrdU, they survived greater than 6 weeks on the pia mater around the spinal cord. Conclusion: Intrathecal transplant of IAST/hPPE cells could alleviate the allodynia-like behaviour after chronic neuropathic pain, which is associated with enkephalin secreted continuously from the grafts and conducted via opiate receptors.