These information indicate that internalization of GLT one and GLAST

Conclusions Our study for the first time selleckchem reveals a mechanism under lying paclitaxel induced acute pain in animals. We iden tify that activation of TLR4 in the spinal dorsal horn and dorsal root ganglions, increased glutamatergic synaptic activities, and reduced glial glutamate transporter activ ities in the spinal dorsal horn are critical events in the genesis of the paclitaxel induced acute pain in animals. Thus, preventing or reversing these abnormalities could potentially prevent and attenuate P APS in patients. Methods and materials Animals Adult male Sprague Dawley rats and 6 8 week old male wild type mice, and TLR4 knockout mice were used. All experiments were approved by the Institutional Animal Care and Use Committee at the University of Georgia and were fully compliant with the National Institutes of Health Guidelines for the Use and Care of Laboratory Animals.<br><br> Drug administration Paclitaxel was injected into rats through Lenalidomide 404950-80-7 the tail vein to mimic the i. v. administration of paclitaxel used in the clinic. Mice received paclitaxel through intraperitoneal injection. Pacli taxel was diluted with saline to make up a volume of 1 ml for rats or 0. 25 ml for mice for injection. Vehicle was composed of the same amounts of Cremophor EL and dehydrated ethanol diluted with saline to the same volume. The experimenter was blind to the type of drugs injected to the animal. Intrathecal drug administration was made either through a pre implanted intrathecal catheter or lumbar puncture.<br><br> To make the implantation of a intrathecal cath eter, a polyethylene catheter that ended at the spinal L4 segment was intrathecally placed following the technique previously described. Briefly, rats were anesthetized under isoflurane and the atlanto occipital membrane was exposed by dissection. LY2228820 価格 A PE 10 catheter was carefully advanced through an opening in the atlanto occipital mem brane to the lumbar enlargement. The wound was then closed in layers. The animals were allowed to recover for 7 days before behavioral tests were conducted. Following be havioral experiments, rats were intrathecally injected with 50 ul of 2% lidocaine. If hind paw paralysis did not ensue, rats were omitted from the experiment. For drug adminis tration through the lumbar puncture, drugs were injected into the intrathecal space at the L5 L6 lumbar interspace in rats anesthetized with 2% isoflurane using a 0.<br><br> 5 inch 30 gauge needle connected to a Hamilton syringe as described previously. Behavioral tests Measurements of mechanical thresholds of hind paw withdrawal responses Behavioral tests were conducted in a quiet room with the room temperature at 22 C. To test possible changes in mechanical sensitivity after a paclitaxel injec tion, rats or mice were placed on a wire mesh, loosely restrained under a plexiglass cage and allowed to acclimate for at least 30 min for rats and 1. 5 h for mice. A series of von Frey monofilaments were tested in ascending order to generate response frequency functions for each animal. Each von Frey filament was applied 5 times to the mid plantar area of each hind paw from beneath for about 1 s. The response frequency for each von Frey filament was determined.