The influence of early-life stress on the coping responses to chronic pain

Abstract

In response to stress, threat or pain, individuals adopt different behavioural and physiological adaptive coping styles. In an animal a model of chronic neuropathic pain, rats show distinct changes social interactions indicative of different styles of coping. In this model, nerve-injured rats develop sensory disturbances, however a sub-population (~30%) display altered social interactions accompanied by neuroendocrine, inflammatory, sleep/wake and neuroanatomical alterations. The hypothalamic-pituitary-adrenal (HPA) axis and its key effector hormone corticosterone is one mechanism by which this combination of changes could be mediated. Variations in the responsivity of this system correlates with different styles of coping to both stress and nerve-injury, suggesting that the HPA axis could also contribute to the individual differences in coping responses to chronic pain. HPA-axis sensitivity can be programmed by early-life events, and early-life stress (ELS) drives differences in individual responses to stress and pain in adulthood. These observations raise the question whether ELS is an important factor in the development of individual differences in coping responses to a chronic nerve-injury. To test this hypothesis, male Sprague-Dawley rat pups received inflammatory ELS at postnatal D3 and D5. At adulthood, the social interactions of each rat were assessed in the nerve injury, neuropathic pain model. The ELS affected the expression of post-injury social interactions, driving the behaviour of individuals to either extremes of the spectrum of coping responses. Systematic investigation of the key structures of hypothalamic-pituitary-adrenal (HPA) axis revealed that behavioural coping styles were associated with distinct changes in pituitary and adrenal hormone-receptor levels. A survey of major inputs to the hypothalamus regulating the HPA revealed that ELS alters corticosterone receptors in the amygdala. These data support the view that ELS plays a role in shaping individual differences in coping with chronic pain, via interactions with the HPA and limbic structures.