Search

Chronic pain affects approximately 20 % of adults worldwide and is often associated with a decrease in the quality of life and various comorbidities. Conventional analgesic therapies are frequently insufficient and sometimes lead to severe side effects. Therefore, great efforts are still being made to elucidate the signalling pathways in pain and to develop new, safe and effective therapies. Epigenetic mechanisms which interfere with the regulation of gene expression are involved in the pathogenesis of several diseases and are gaining increasing impetus in medical research. As they are also involved in pain processing, a modulation of these mechanisms might represent a novel option for the therapy of pain patients.

The site of hormone action is the cells of target tissues. Now that ultrastructural research has revealed the complexity of eukaryotic cells, we must ask which cellular structures are involved. Some hormones act at the cell membrane, mainly via adenylate cyclase and the "second messenger" cAMP. The cytosol and the mitochondria, the main sites of intermediate metabolism and enzyme activity, are apparently not involved, although in the past interaction of hormones with enzymes has been postulated. Most of the steroid hormones act at the level of the cell nucleus, regulating transcription of specific genes and inducing enzymes or other proteins. The mechanisms by means of which this regulation is achieved are not fully understood, but it is likely that derepression is involved. The active agent seems to be a complex of the hormone with a receptor protein.

Experimental evidence for a role of histones and chromosomal nonhistone proteins in the regulation of transcription in eucaryots is described. A speculative model on the regulation of gene activity in higher organisms is presented.