Hi, If you read the first article it talks about sodium channels.

According to Cruciani, constant pain signals from the periphery may lead to changes in the posterior horn of the spinal cord, such as an increase in the number of N-methyl-d-aspartic acid (NMDA) receptors that bind glutamate, an increase in the number of certain types of sodium channels, or a change in the expression of the calcitonin gene-related peptide. An increase in proinflammatory cytokines also has been identified



Sodium Channels as Molecular Targets in Pain Research

Given what we have learned about sodium channels, where do we go next in the search for better treatments for pain syndromes? The answer to this question is not entirely clear at this time. We can, however, come to a number of conclusions. First, sodium channels are important participants in electrogenesis within primary sensory neurons, including DRG neurons. Second, a multiplicity of sodium channels are present within DRG neurons, where they probably subserve multiple functions (transduction, signal amplification, action potential electrogenesis, etc.) and interact in a complex manner. Third, DRG neurons express a number of sodium channel genes (SNS/PN3, NaN, PN1, and NaG) in a preferential manner, at levels much higher than in any other neuronal cell type. This observation may present a therapeutic opportunity for the selective manipulation of primary sensory neurons in general, or nociceptive neurons in particular. Fourth, sodium channel expression in DRG neurons is highly dynamic, with multiple sodium channel genes (including -III, SNS/PN3, and NaN) exhibiting up- or down-regulation after various injuries to these cells. Importantly, different injuries may trigger opposing changes of certain sodium channel genes (e.g., down-regulation of SNS/PN3 after axotomy vs. up-regulation in the carageenan inflammation model) in DRG neurons, so that it may be difficult to extrapolate from one model system to another. Nevertheless, we have learned, at a minimum, that sodium channel expression in DRG neurons is dynamic and can change significantly after injury, and that changes in sodium channel expression can substantially alter excitability in these cells.

Delineation of the precise role(s) of each sodium channel subtype in the physiology of DRG neurons and the pathophysiology of pain remains to be established, and the utility of selective blockade of each channel subtype as an approach to the treatment of pain will require further careful study. However, the stage has been set for these investigations. It is quite likely, in our opinion, that sodium channel blockade will emerge as a viable strategy for pharmacologic treatment of pain.

http://www.pnas.org/cgi/content/full/96/14/7635