Trends in neurosciences
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Gephyrin is a multifunctional protein responsible for molybdenum cofactor synthesis and the clustering of glycine and GABA(A) receptors at inhibitory synapses. Based on the structure of its two conserved domains, G and E, gephyrin is thought to form a hexagonal lattice serving as a scaffold for accessory proteins at postsynaptic sites. ⋯ Here we review the current state of knowledge about gephyrin, highlighting new research avenues based on a different structural model and a revised nomenclature for gephyrin splice variants. Unraveling the biology of gephyrin will further our understanding of glycinergic and GABAergic synapses in health and disease.
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Investigation of the basic mechanisms of chronic pain not only provides insights into how the brain processes and modulates sensory information but also provides the basis for designing novel treatments for currently intractable clinical conditions. Human brain imaging studies have revealed new roles of cortical neuronal networks in chronic pain, including its unpleasant quality, and mouse studies have provided molecular and synaptic mechanisms underlying relevant cortical plasticity. This review paper will critically examine the current literature and propose a cortical network model for chronic pain.
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Gain-of-function mutations or dysregulated expression of voltage-gated sodium channels can produce neuronal hyperexcitability, leading to acute or chronic pain. The sodium channel Na(v)1.7 is expressed preferentially in most slowly conducting nociceptive neurons and in sympathetic neurons. Gain-of-function mutations in the Na(v)1.7 channel lead to DRG neuron hyperexcitability associated with severe pain, whereas loss of the Na(v)1.7 channel in patients leads to indifference to pain. The contribution of Na(v)1.7 to acquired and inherited pain states and the absence of motor, cognitive and cardiac deficits in patients lacking this channel make it an attractive target for the treatment of neuropathic pain.
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Trends in neurosciences · Feb 2005
ReviewNeuropathic pain and spinal microglia: a big problem from molecules in "small" glia.
Neuropathic pain is a common and severely disabling state that affects millions of people worldwide. Such pain can be experienced after nerve injury or as part of diseases that affect peripheral nerve function, such as diabetes and AIDS; it can also be a component of pain in other conditions, such as cancer. ⋯ It is important to establish how these molecules are activated in spinal microglia following nerve injury and how they cause signaling to neurons in the dorsal horn pain transmission network. Answers to these questions could lead to new strategies that assist in the diagnosis and management of neuropathic pain--strategies not previously anticipated by a neuron-centric view of pain plasticity in the dorsal horn.