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Rationale: Gaps in our understanding of glutamatergic signaling may be key obstacles in accurately modeling complex CNS diseases. System xc (-) is an example of a poorly understood component of glutamate homeostasis that has the potential to contribute to CNS diseases., Objectives: This study aims to determine whether system xc (-) contributes to behaviors used to model features of CNS disease states., Methods: In situ hybridization was used to map mRNA expression of xCT throughout the brain. Microdialysis in the prefrontal cortex was used to sample extracellular glutamate levels; HPLC was used to measure extracellular glutamate and tissue glutathione concentrations. Acute administration of sulfasalazine (8-16 mg/kg, IP) was used to decrease system xc (-) activity. Behavior was measured using attentional set shifting, elevated plus maze, open-field maze, Porsolt swim test, and social interaction paradigm., Results: The expression of xCT mRNA was detected throughout the brain, with high expression in several structures including the basolateral amygdala and prefrontal cortex. Doses of sulfasalazine that produced a reduction in extracellular glutamate levels were identified and subsequently used in the behavioral experiments. Sulfasalazine impaired performance in attentional set shifting and reduced the amount of time spent in an open arm of an elevated plus maze and the center of an open-field maze without altering behavior in a Porsolt swim test, total distance moved in an open-field maze, or social interaction., Conclusions: The widespread distribution of system xc (-) and involvement in a growing list of behaviors suggests that this form of nonvesicular glutamate release is a key component of excitatory signaling.

In an open three-center pilot study, 17 patients suffering from chronic persistent pain syndrome, due to osteoarthritis of the hip and knee or spondylarthrosis, were treated orally with 1800-2400 mg Ibuprofen per day for 3 weeks. The chronic pain syndrome and joint status were assessed by the physician at the beginning, and after 7, 14 and 21 days. Self-assessments were made by the patients six times daily during the full study period by means of battery-driven electronic diaries (E.D.). The data entered by the patients were stored in the E.D. and after online transfer, processed and evaluated in a PC using appropriate software programs. E.D. were returned by 16 of 17 patients for evaluation. The technical functioning of the instrument was perfect; its use was accepted by patients and physicians. The closely-meshed real-time recording of pain course and other subjective data, such as adverse events or medication, etc., enables the physician to calculate more exactly and reliably improvement rates, as well as to carry out prognostic trend analyses and individual benefit-risk-ratio estimates. By comparing different kinds of data, each entered at the same time, plausibility checks are possible. The procedure presented here is considered to be a new valuable tool for reviewing subjective data from clinical drug trials.

Nineteen patients with chronic pain due to a traumatic peripheral neuropathy were treated by means of implanted nerve stimulation. In 11 (58%) pain was completely relieved and in four (21%) it was reduced sufficiently to discontinue analgesics. The average follow-up was 11.5 months. The technique is described and the failures discussed. The necessity for implanting the stimulator proximally is emphasised.