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UNLABELLED Na+ channels are large transmembrane proteins with a voltage-gated central pore capable of selectively passing Na+ ions. They are critical determinants of the electrical excitability of sensory neurons and play a key role in pain sensation by controlling afferent impulse discharge. Injury and disease affecting peripheral nerves induces axonopathy(More)
Clinical pain syndromes, and experimental assays of nociception, are differentially affected by manipulations such as drug administration and exposure to environmental stress. This suggests that there are different 'types' of pain. We exploited genetic differences among inbred strains of mice in an attempt to define these primary 'types'; that is, to(More)
Concussion, asphyxia, and systemically administered general anesthetics all induce reversible depression of the organism's response to noxious stimuli as one of the elements of loss of consciousness. This is so even for barbiturate anesthetics, which have only modest analgesic efficacy at subanesthetic doses. Little is known about the neural circuits(More)
Ectopic discharge in axotomized dorsal root ganglion neurons is a key driver of neuropathic pain. However, the bulk of this activity is generated and carried centrally in large diameter myelinated Abeta afferents, a cell type that normally signals touch and vibration sense. Evidence is considered suggesting that following axotomy, Abeta afferents undergo a(More)
Heat sensitivity shows considerable functional variability in humans and laboratory animals, and is fundamental to inflammatory and possibly neuropathic pain. In the mouse, at least, much of this variability is genetic because inbred strains differ robustly in their behavioral sensitivity to noxious heat. These strain differences are shown here to reflect(More)
Only a generation ago there were few ideas as to what might cause neuropathic pain, and even fewer relevant data. In contrast, we can currently point to hundreds of distinct cellular changes that are triggered by nerve injury and that might be relevant to the emergence of pain symptomatology. The number may soon increase to thousands. It is essential,(More)
BACKGROUND Nerve injury-triggered hyperexcitability in primary sensory neurons is considered a major source of chronic neuropathic pain. The hyperexcitability, in turn, is thought to be related to transcriptional switching in afferent cell somata. Analysis using expression microarrays has revealed that many genes are regulated in the dorsal root ganglion(More)
Patients who have suffered nerve injury show profound inter-individual variability in neuropathic pain even when the precipitating injury is nearly identical. Variability in pain behavior is also observed across inbred strains of mice where it has been attributed to genetic polymorphisms. Identification of cellular correlates of pain variability across(More)
OBJECT Recent progress in the understanding of abnormal electrical behavior in injured sensory neurons motivated an examination, at the ultrastructural level, of trigeminal roots of patients with trigeminal neuralgia (TN). METHODS In 12 patients biopsy specimens of trigeminal root were obtained during surgery for microvascular decompression. Pathological(More)