Progress in molecular biology and translational science
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Prog Mol Biol Transl Sci · Jan 2016
ReviewGH and Pituitary Hormone Alterations After Traumatic Brain Injury.
Traumatic brain injury (TBI) is a crucially important public health problem around the world, which gives rise to increased mortality and is the leading cause of physical and psychological disability in young adults, in particular. Pituitary dysfunction due to TBI was first described 95 years ago. However, until recently, only a few papers have been published in the literature and for this reason, TBI-induced hypopituitarism has been neglected for a long time. ⋯ Patients with TBI without neuroendocrine changes and those with TBI-induced hypopituitarism share the same clinical manifestations, such as attention deficits, impulsion impairment, depression, sleep abnormalities, and cognitive disorders. For this reason, TBI-induced hypopituitarism may be neglected in TBI victims and it would be expected that underlying hypopituitarism would aggravate the clinical picture of TBI itself. Therefore, the diagnosis and treatment of unrecognized hypopituitarism due to TBI are very important not only to decrease morbidity and mortality due to hypopituitarism but also to alleviate the chronic sequelae caused by TBI.
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Prog Mol Biol Transl Sci · Jan 2015
ReviewCommonalities between pain and memory mechanisms and their meaning for understanding chronic pain.
Pain sensing neurons in the periphery (called nociceptors) and the central neurons that receive their projections show remarkable plasticity following injury. This plasticity results in amplification of pain signaling that is now understood to be crucial for the recovery and survival of organisms following injury. These same plasticity mechanisms may drive a transition to a nonadaptive chronic pain state if they fail to resolve following the termination of the healing process. ⋯ Here those mechanisms, their commonalities and subtle differences, will be highlighted and their role in causing chronic pain will be discussed. Arising from these data is the striking argument that chronic pain is a disease of the nervous system, which distinguishes this phenomena from acute pain that is frequently a symptom alerting the organism to injury. This argument has important implications for the development of disease modifying therapeutics.
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Prog Mol Biol Transl Sci · Jan 2015
ReviewRegulation of gene expression and pain states by epigenetic mechanisms.
The induction of inflammatory or neuropathic pain states is known to involve molecular activity in the spinal superficial dorsal horn and dorsal root ganglia, including intracellular signaling events which lead to changes in gene expression. These changes ultimately cause alterations in macromolecular synthesis, synaptic transmission, and structural architecture which support central sensitization, a process required for the establishment of long-term pain states. Epigenetic mechanisms are essential for long-term synaptic plasticity and modulation of gene expression. ⋯ This chapter draws upon other specialities which have extensively investigated epigenetic mechanisms, such as learning and memory and oncology. After defining epigenetics as well as the recent field of "neuroepigenetics" and the main molecular mechanisms involved, this chapter describes the role of these mechanisms in the synaptic plasticity seen in learning and memory, and address those epigenetic mechanisms that have been linked with the development of acute and prolonged pain states. Finally, the idea that long-lasting epigenetic modifications could contribute to the transition from acute to chronic pain states by supporting maladaptive molecular changes is discussed.
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The failure of neuropathic pain to abate even years after trauma suggests that adverse changes to synaptic function must exist in a chronic pathological state in nociceptive pathways. The chronicity of neuropathic pain therefore underscores the importance of understanding the contribution of dendritic spines--micron-sized postsynaptic structures that represent modifiable sites of synaptic contact. Historically, dendritic spines have been of great interest to the learning and memory field. ⋯ Because of the relationship between dendritic spine structure and neuronal function, a thorough investigation of dendritic spine behavior in the spinal cord is a unique opportunity to better understand the mechanisms of sensory dysfunction after injury or disease. At a conceptual level, a spinal memory mechanism that engages dendritic spine remodeling would also contribute to a broad range of intractable neurological conditions. Molecules involved in regulating dendritic spine plasticity may offer novel targets for the development of effective and durable therapies for neurological disease.
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Prog Mol Biol Transl Sci · Jan 2015
ReviewSynaptic inhibition and disinhibition in the spinal dorsal horn.
Nociceptive signals originating in the periphery must be transmitted to the brain to evoke pain. Rather than being conveyed unchanged, those signals undergo extensive processing in the spinal dorsal horn. Synaptic inhibition plays a crucial role in that processing. ⋯ To that end, this chapter will discuss the structure and function of GABAA and glycine receptors together with the role of associated molecules involved in transmitter handling and chloride regulation. Mechanisms by which inhibition modulates cellular excitability will be described. The chapter will end with discussion of how inhibition goes awry under pathological conditions and what the implications are for the treatment of resulting pain.