In these instances, it is now technically possible to conduct ChI

In these instances, it is now technically possible to conduct ChIP and DNA methylation studies after selecting fluorescently tagged cell types with flow cytometry (Guo et al., 2011 and Jiang et al., 2008). In addition to basic research,

there is the potential for the study of epigenetics to reveal novel drug targets for the treatment of pain. It is already clear from only a Bortezomib few experiments that HDAC inhibitors might be an interesting group of drugs to explore. Currently, these compounds display limited selectivity or, more precisely, a selectivity bias toward the ubiquitously expressed class I HDACs (Bradner et al., 2010). As a consequence, if given systemically, many adverse side effects, such as fatigue, nausea, and diarrhea, can occur. Nevertheless, two HDAC inhibitors (vorinostat and romidepsin) are already approved for use in the clinic against T cell lymphoma, and many more are being trialed as chemotherapeutic agents (Lemoine and Younes, 2010). Because of their relevance in the fight against cancer,

development of more selective and hence more tolerable HDAC inhibitors is a high priority not only CB-839 concentration for research but also for the pharmaceutical industry. In the pain field, drugs specifically targeting class IIa HDACs would be of particular interest. This class is expressed less widely, and some evidence suggests that one of its members (HDAC4) is implicated in pain processing. Thus, Rajan et al. (2009) reported that knockout of the HDAC4 deacetylase domain in mice decreases their thermal sensitivity on a hot plate (Rajan et al., 2009). It will also be of great interest to test the effects of other groups of compounds, for instance, those interfering with the actions of histone acetyltransferases or lysine methyltransferases. These enzymes add acetyl or methyl groups to histones (as well as other proteins) and tend to be more selective in the residues they modify, potentially making them better targets for drug development than deacetyl-

or demethylases (Copeland et al., Mephenoxalone 2009 and Dekker and Haisma, 2009). Finally, many of the epigenetic “reader proteins” (Table 1) could be viable drug targets, since their precise involvement is likely to be disease-process and situation specific. Hence, a deeper knowledge of epigenetic processes in chronic pain is needed to gauge their therapeutic potential. The currently available data suggest that epigenetic mechanisms may be important contributors to chronic pain states. Descriptive studies, for instance examination of genome-wide histone acetylation or methylation in various models of chronic pain, will be useful and are certainly feasible. Causal interactions may take longer to establish, but a wide variety of compounds, targeting specific epigenetic proteins, are being developed and will greatly facilitate this effort.

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