Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Aug 2012
ReviewMoving toward a generalizable application of central thalamic deep brain stimulation for support of forebrain arousal regulation in the severely injured brain.
This review considers the challenges ahead for developing a generalizable strategy for the use of central thalamic deep brain stimulation (CT/DBS) to support arousal regulation mechanisms in the severely injured brain. Historical efforts to apply CT/DBS to patients with severe brain injuries and a proof-of-concept result from a single-subject study are discussed. Circuit and cellular mechanisms underlying the recovery of consciousness are considered for their relevance to the application of CT/DBS, to improve consciousness and cognition in nonprogressive brain injuries. Finally, directions for development, and testing of generalizable criteria for CT/DBS are suggested, which aim to identify neuronal substrates and behavioral profiles that may optimally benefit from support of arousal regulation mechanisms.
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Ann. N. Y. Acad. Sci. · Aug 2012
Deep brain stimulation for movement and other neurologic disorders.
Deep brain stimulation (DBS) was introduced as a treatment for patients with parkinsonism and other movement disorders in the early 1990s. The technique rapidly became the treatment of choice for these conditions, and is now also being explored for other diseases, including Tourette syndrome, gait disorders, epilepsy, obsessive-compulsive disorder, and depression. ⋯ Despite the progress made in the use of DBS, much remains to be done to fully realize the potential of this therapy. We describe some of the most active areas of research in this field, both in terms of exploration of new targets and stimulation parameters, and in terms of new electrode or stimulator designs.
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Ann. N. Y. Acad. Sci. · Jul 2012
ReviewExperimental endotoxemia as a model to study neuroimmune mechanisms in human visceral pain.
The administration of bacterial endotoxin (i.e., lipopolysaccharide, LPS) constitutes a well-established experimental approach to study the effects of an acute and transient immune activation on physiological, behavioral, and emotional aspects of sickness behavior in animals and healthy humans. However, little is known about possible effects of experimental endotoxemia on pain in humans. ⋯ Considering the recent findings of visceral hyperalgesia after LPS application in humans, in this review, we propose that experimental endotoxemia with its complex peripheral and central effects constitutes an experimental model to study neuroimmune communication in human pain research. We summarize and attempt to integrate relevant animal and human studies concerning neuroimmune communication in visceral and somatic pain, discuss putative mechanisms, and conclude with future research directions.
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Ann. N. Y. Acad. Sci. · Jun 2012
Modulation of tight junction proteins in the perineurium for regional pain control.
Peripheral neurons are surrounded by the perineurium that forms the blood-nerve barrier and protects the nerve. Although the barrier serves as protection, it also hampers drug delivery of analgesic drugs to the peripheral nerve. We previously showed that opening of the barrier using hypertonic solutions facilitates drug delivery, for example, of hydrophilic opioids, which selectively target nociceptors. ⋯ After several days, tight junction proteins reappear and the barrier reseals. Similarly, perineurial injection of hypertonic saline transiently opens the barrier, claudin-1 disappears, and hydrophilic analgesic drugs are effective. In the future, these findings could be used to reseal the barrier breakdown and could be applied to other barriers like the blood-brain or the intestinal mucosal barrier.