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Uptake of L-glutamate into synaptic vesicles is mediated by vesicular glutamate transporters (VGLUTs). Three transporters (VGLUT1-VGLUT3) are expressed in the mammalian CNS, with partial overlapping expression patterns, and VGLUT2 is the most abundantly expressed paralog in the thalamus, midbrain, and brainstem. Previous studies have shown that VGLUT1 is(More)
Although vascular endothelial growth factor-B (VEGF-B) is a homolog of the angiogenic factor VEGF, it has only minimal angiogenic activity, raising the question of whether this factor has other (more relevant) biological properties. Intrigued by the possibility that VEGF family members affect neuronal cells, we explored whether VEGF-B might have a role in(More)
Comparative studies of the benzisoxazole derivative risperidone (R 64 766) were made with ritanserin, a selective centrally acting serotonin-S2 antagonist and with haloperidol, a selective centrally acting dopamine-D2 antagonist. Risperidone like ritanserin shows activity in all tests related to serotonin-S2 antagonism, but at even lower doses (peripheral(More)
Mu-opioid analgesics are a mainstay in the treatment of acute and chronic pain of multiple origins, but their side effects, such as constipation, respiratory depression, and abuse liability, adversely affect patients. The recent demonstration of the up-regulation and membrane targeting of the delta-opioid receptor (DOR) following inflammation and the(More)
The TRPA1 channel is activated by a number of pungent chemicals, such as allylisothiocyanate, present in mustard oil and thiosulfinates present in garlic. Most of the known activating compounds contain reactive, electrophilic chemical groups, reacting with cysteine residues in the active site of the TRPA1 channel. This covalent modification results in(More)
Two voltage gated sodium channels, Na(v)1.8 and Na(v)1.9, are exclusively expressed in primary sensory neurons and are suggested to play a role in different pain conditions, including chronic inflammatory and neuropathic pain states. Since no selective pharmacological tools are available, we investigated the involvement of Na(v)1.8 and Na(v)1.9 in pain(More)
Described here is a comparison of five peripheral sciatic nerve injury models in rats which all result in various degrees of neuropathic pain symptoms. They are the chronic constriction injury (CCI), the spinal nerve ligation (SNL), the partial sciatic ligation (PSL), the tibial and sural transection (TST), and the complete sciatic transection (CST) model.(More)
Substantial evidence indicates an association between clinical depression and altered immune function. Systemic administration of bacterial lipopolysaccharide (LPS) is commonly used to study inflammation-associated behavioral changes in rodents. In these experiments, we tested the hypothesis that peripheral immune activation leads to neuroinflammation and(More)
Systemic vascular endothelial growth factor inhibition, in combination with chemotherapy, improves the outcome of patients with metastatic cancer. Peripheral sensory neuropathies occurring in patients receiving both drugs are attributed to the chemotherapy. Here, we provide unprecedented evidence that vascular endothelial growth factor receptor inhibitors(More)
The dose-limiting side effect of the anti-neoplastic agent, paclitaxel, is a chronic distal symmetrical peripheral neuropathy that produces sensory dysfunction (hypoesthesia and neuropathic pain) but little or no distal motor dysfunction. Similar peripheral neuropathies are seen with chemotherapeutics in the vinca alkaloid, platinum-complex, and proteasome(More)