Attenuation of responses to repeated sensory events has been thoroughly studied in many modalities; however, attenuation of pain perception has not yet benefitted from such extensive investigation. Described here are two psychophysical studies that examined the effects of repeated exposure to thermal stimuli, assessing potential attenuation of the perception of pain and its possible spatial specificity. Twenty-two subjects were presented thermal stimuli to the volar surface of the right and left forearms. Twelve subjects in study 1 received the same stimuli and conditions on each of five daily experimental sessions, whereas 10 subjects in study 2 received thermal stimuli, which were restricted to one side for four daily sessions and then applied to the other side on the fifth session. Ratings of warmth intensity, pain intensity, and pain unpleasantness were recorded while the subjects performed a thermal sensory discrimination task. Results of study 1 demonstrate that repeated stimulation with noxious heat can lead to long-term attenuation of pain perception; results of study 2 extend these findings of attenuation to both pain intensity and unpleasantness and show that this effect is highly specific to the exposed body side for both aspects of the pain experience. We suggest that the functional plasticity underlying this attenuation effect lies in brain areas with a strong contralateral pattern of pain-related activation.

Chemotherapy has had little impact in the treatment of malignant gliomas of astrocytic lineage thus far. 1 T h e shortcomings of chemotherapy have generally been attributed to two factors, namely intrinsic glial cell resistance to chemotherapy agents, and the physiological impediment ABSTRACT: Objective: We propose a simple modification to an established blood-brain barrier disruption (BBBD) animal model that allows us to use ketamine/xylazine as the anaesthetic agent, therefore decreasing the complexity and the cost of the model, while maintaining similar efficiency. Methods: Sixty-two Long Evans rats were anaesthetized by intraperitoneal injection of ketamine/ xylazine. Osmotic BBBD was performed by administering 25% mannitol into the internal carotid artery in a retrograde fashion from the external carotid. The infusion rate of mannitol, as well as the duration was adjusted in a stepwise fashion to identify optimal parameters for BBBD and minimize complications. As a supplementary step to previously reported models, a vascular clip was applied to the common carotid artery prior to the infusion of mannitol, therefore isolating our model system from the depressant hemodynamic effects of ketamine/xylazine. Evans blue dye was used to control for BBBD intensity. Results: Using this model at an initial infusion rate of 0.15 ml/sec, a significant incidence of brain hemorrhage (75%) and a death rate of 62.5% were observed. Decreasing the infusion rate in a stepwise fashion, 0.08 ml/sec was found to produce optimal BBBD, as demonstrated by Evans blue staining. At this rate, 6/7 animals depicted grade II staining, whereas one animal depicted grade IV. Conclusion:The application of a clip to the common carotid artery prior to mannitol infusion allowed us to isolate the cerebral circulation from the depressant hemodynamic effects of ketamine/xylazine. This supplementary step produced consistent and efficient BBBD in our animal model. RÉSUMÉ: Modèle de perturbation de la barrière hémato-encéphalique éliminant l'effet hémodynamique de la kétamine. Objectif: Nous proposons une modification simple à un modèle animal établi de perturbation de la barrière hémato-encéphalique (PBHE) qui nous permet d'utiliser la kétamine/xylazine comme anesthésique, ce qui diminue la complexité et le coût du modèle tout en maintenant une efficacité similaire. Méthodes: Soixante-deux rats Long Evans ont été anesthésiés par injection intrapéritonéale de kétamine/xylazine. La PBHE a été effectuée en administrant du mannitol 25% dans la carotide interne par injection rétrograde, à partir de la carotide externe. La vitesse et la durée d'infusion du mannitol étaient ajustées par paliers afin d'identifier les paramètres optimaux et de minimiser les complications de la PBHE. Une étape supplémentaire a été ajoutée au modèle, soit l'application d'un clip vasculaire au niveau de la carotide primitive avant l'infusion du mannitol, isolant ainsi le modèle des effets de dépression hémodynamique de la kétamine/xylazine. L'intensité de la PBHE a été évaluée pa...