Does epigenetic ‘memory’ of early-life stress predispose to chronic pain in later life? A potential role for the stress regulator FKBP5

Animal behaviours are affected not only by inherited genes but also by environmental experiences. For example, in both rats and humans, stressful early-life events such as being reared by an inattentive mother can leave a lasting trace and affect later stress response in adult life. This is owing to a chemical trace left on the chromatin attributed to so-called epigenetic mechanisms. Such an epigenetic trace often has consequences, sometimes long-lasting, on the functioning of our genes, thereby allowing individuals to rapidly adapt to a new environment. One gene under such epigenetic control isFKBP5 , the gene that encodes the protein FKPB51, a crucial regulator of the stress axis and a significant driver of chronic pain states. In this article, we will discuss the possibility that exposure to stress could drive the susceptibly to chronic painvia epigenetic modifications of genes within the stress axis such asFKBP5 . The possibility that such modifications, and therefore, the susceptibility to chronic pain, could be transmitted across generations in mammals and whether such mechanisms may be evolutionarily conserved across phyla will also be debated.This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.