Change In Expression Of Fractalkine MRNA In Spinal Cord And Dorsal Root Ganglia In Paclitaxel-induced Neuropathic Rats

BackgroudPaclitaxel chemotherapy often causes intractable neuropathic pain and the mechanism under this neuropathic pain is not sure. From previous researches, activation of microglia in the spinal cord is involved in paclitaxel-induced painful peripheral neuropathy. Fractalkine is predominantly expressed in CNS neurons. Its unique receptor, CX3CR1, is mainly expressed in microglia. Such complementary distribution suggest that Fractalkine/CX3CR1 play a role in the regulation of microglia activation. A number of evidence indicate that Fractalkine/CX3CR1 is involved in neuropathic pain induced by nerve injury and inflammation. Meanwhile, some research indicate an anti-allodynic role and/or neuroprotection of Fractalkine and its receptor. Whether Fractalkine is involved in paclitaxel-induced painful peripheral neuropathy and what role they play in this neuropathy is largly unknown.ObjectiveThis experiment is designed to explore whether Fractalkine is involved in paclitaxel-induced painful peripheral neuropathy, by detecting Fractalkine mRNA expression in the lumbar spinal cord and DRG. Methods1. To establish the rat model of paclitaxel-induced painful peripheral neuropathy 20 adult male SD rats(240~260g) were randomly divided into 2 groups, PN group(paclitaxel-induced peripheral neuropathy, received paclitaxel, n=10), CON group(received vehicle, n=10). In this experiment, adult male rats were given four intraperitoneal injections on alternate days (day1, 3, 5, 7)of 1.0mg/kg of paclitaxel (Taxol), according methods described by Polomano Rosemary C. (2001). CON group were received vehicle(the vehicle was a mixture of 0.9% saline and Cremophor EL). The rats were tested for mechanical allodynia and thermal withdrawal latency respectively by the method of up-down and Hargreaves at the days 1, 2, 4, 6, 8, 9, 10, 12, 14. In this way we can observe the onset and development of pathological process.2. To detect the Fractalkine mRNA expression in the lumbar spinal cord and DRG Rats were sacrificed after anesthetized with 10% chloral hydrate on day 14. Lumbar spinal cord and DRG were sampled for later detection of Fractalkine mRNA expression by Realtime-PCR.Results1. We have successfully established the rat model of paclitaxel-induced painful peripheral neuropathy. After injection of paclitaxel, mechanical allodynia and heat-hyperalgesia developed gradually in PN group. Both reached to a lowest point on day14. From the data measured, mechanical allodynia threshold in PN group was lower than that of CON group at day 4, 8, 9(P<0.05), and significantly lower at day 6, 10, 12, 14(P<0.01).Meanwhile the TWL of PN group was shorter than that of CON group at day 6, 9, 10(P<0.05), and significantly shorter at day 4, 8, 12, 14(P<0.01).2. Realtime-PCR show that the expression of Fractalkine mRNA in lumbar spinal cord is down-regulated in PN group(P<0.05), compared to CON group; also the expression of Fractalkine mRNA in DRG is down-regulated in PN group(P<0.01), compared to CON group. ConclusionThe rat model of paclitaxel-induced painful peripheral neuropathy was established successfully. The expression of Fractalkine mRNA in lumbar spinal cord is down-regulated in PN group(P<0.05)compared to CON group, and the expression of Fractalkine mRNA in DRG is down-regulated in PN group(P<0.01) compared to CON group. It may suggest that Fractalkine is involved in the paclitaxel-induced painful peripheral neuropathy, the neuroprotection role of Fractalkine is down-regulated and result in facilitating paclitaxel-induced painful peripheral neuropathy.