Sheng li xue bao : [Acta physiologica Sinica]
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Neurofibromatosis type 1 (NF1) is a common autosomal dominant disease characterized by formation of multiple benign and malignant tumors. People with this disorder also experience chronic pain, which can be disabling. Neurofibromin, the protein product of the Nf1 gene, is a guanosine triphosphatase activating protein (GAP) for p21Ras (Ras). ⋯ Consistent with that observation, neurons from Nf1+/- mice had lower firing thresholds, lower rheobase currents and shorter firing latencies compared with wildtype neurons. These data clearly demonstrate that GAPs, such as neurofibromin, can alter the excitability of nociceptive sensory neurons. The augmented response of sensory neurons with altered Ras signaling may explain the abnormal pain sensations experienced by people with NF1 and suggests an important role of GAPs in the mechanism of sensory neuron sensitization.
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Artemin is a neuronal survival and differentiation factor in the glial cell line-derived neurotrophic factor family. Its receptor GFRalpha3 is expressed by a subpopulation of nociceptor type sensory neurons in the dorsal root and trigeminal ganglia (DRG and TG). These neurons co-express the heat, capsaicin and proton-sensitive channel TRPV1 and the cold and chemical-sensitive channel TRPA1. ⋯ These findings indicate that artemin can modulate sensory function and that this regulation may occur through changes in channel gene expression. Because artemin mRNA expression is up-regulated in inflamed tissue and following nerve injury, it may have a significant role in cellular changes that underlie pain associated with pathological conditions. Manipulation of artemin expression may therefore offer a new pain treatment strategy.