Nature neuroscience
-
There are many known risk factors for chronic pain conditions, yet the biological underpinnings that link these factors to abnormal processing of painful signals are only just beginning to be explored. This Review will discuss the potential mechanisms that have been proposed to underlie vulnerability and resilience toward developing chronic pain. Particular focus will be given to genetic and epigenetic processes, priming effects on a cellular level, and alterations in brain networks concerned with reward, motivation/learning and descending modulatory control. Although research in this area is still in its infancy, a better understanding of how pain vulnerability emerges has the potential to help identify individuals at risk and may open up new therapeutic avenues.
-
Nature neuroscience · Feb 2014
ReviewRegulating excitability of peripheral afferents: emerging ion channel targets.
The transmission and processing of pain signals relies critically on the activities of ion channels that are expressed in afferent pain fibers. This includes voltage-gated channels, as well as background (or leak) channels that collectively regulate resting membrane potential and action potential firing properties. ⋯ Over the past few years, a number of different types of ion channels have been implicated in afferent pain signaling. Here we give an overview of recent advances on sodium, calcium, potassium and chloride channels that are emerging as especially attractive targets for the treatment of pain.
-
Autophagy is essential for neuronal homeostasis, and its dysfunction has been directly linked to a growing number of neurodegenerative disorders. The reasons behind autophagic failure in degenerating neurons can be very diverse because of the different steps required for autophagy and the characterization of the molecular players involved in each of them. Understanding the step(s) affected in the autophagic process in each disorder could explain differences in the course of these pathologies and will be essential to developing targeted therapeutic approaches for each disease based on modulation of autophagy. Here we present examples of different types of autophagic dysfunction described in common neurodegenerative disorders and discuss the prospect of exploring some of the recently identified autophagic variants and the interactions among autophagic and non-autophagic proteolytic systems as possible future therapeutic targets.
-
Nociceptive pain results from the detection of intense or noxious stimuli by specialized high-threshold sensory neurons (nociceptors), a transfer of action potentials to the spinal cord, and onward transmission of the warning signal to the brain. In contrast, clinical pain such as pain after nerve injury (neuropathic pain) is characterized by pain in the absence of a stimulus and reduced nociceptive thresholds so that normally innocuous stimuli produce pain. The development of neuropathic pain involves not only neuronal pathways, but also Schwann cells, satellite cells in the dorsal root ganglia, components of the peripheral immune system, spinal microglia and astrocytes. As we increasingly appreciate that neuropathic pain has many features of a neuroimmune disorder, immunosuppression and blockade of the reciprocal signaling pathways between neuronal and non-neuronal cells offer new opportunities for disease modification and more successful management of pain.
-
The development of new treatments for depression is predicated upon identification of neural substrates and mechanisms that underlie its etiology and pathophysiology. The heterogeneity of depression indicates that its origin may lie in dysfunction of multiple brain regions. ⋯ We next revisit the functional differentiation of the hippocampus along the septo-temporal axis within the context of adult hippocampal neurogenesis and suggest that neurogenesis in the ventral dentate gyrus may be preferentially involved in regulation of emotion. Finally, we speculate on how increased adult hippocampal neurogenesis may modulate dentate gyrus function to confer the behavioral effects of antidepressants.