Pain in Special Populations

Painful experiences (e.g. surgeries, injuries) can be traumatic for individuals of any age, but adverse experiences and trauma in early life of humans and other mammals appear to have an important role in the development of enduring pain problems. Surprisingly little research has examined the trauma-pain relationship in early life or the underlying mechanisms that drive this over time, although it is evident that adverse early experience ‘sets’ the organism to anticipate high levels of threat and to be appropriately ready to mobilise defences, including pain. The focus of research has largely been on synergistic interactions of traumatic stress and pain in adulthood, both in terms of brain processing and of behaviour, and how to address either or both in treatment.

We will examine the relationships between physical and emotional trauma and pain across infancy, childhood, adolescence and adulthood, as well as the neurobiological, cognitive, behavioural, and interpersonal mechanisms that drive this relationship over time. New empirical findings will be rooted in recent and emerging evolutionary, cognitive-behavioural, and neurobiological models of trauma and pain and will inform advances in the prevention and treatment of pain and trauma across the lifespan.

Children with chronic pain and their parents experience trauma symptoms at much higher rates than non-pain populations and trauma is linked to worse pain and functioning. Conceptual models of mutual maintenance posit that neurobiological, cognitive-behavioral, and interpersonal factors drive this relationship, but this has not yet been empirically shown in prospective research. Dr. Noel will present new prospective data from a cohort of treatment-seeking youth with chronic pain and their parents (N=200) integrating methods in brain-imaging eye-tracking, ecological momentary assessment, and activity monitoring demonstrating the roles of brain activation, cognitive biases, sleep disturbances and parent factors in the co-occurrence and maintenance of trauma (ACEs, PTSD) and pediatric chronic pain. Data demonstrating epigenetic and behavioural (parenting responses, sleep disturbances) mechanisms underlying the intergenerational  transmission of risk for pediatric chronic pain across generations will be presented. This will parallel preclinical findings from rodent model presented by co-presenter Dr. Mychasiuk. Overlapping epigenetic factors yielded from combining the animal and human models will be identified. New birth cohort data examining the role of parent ACEs in pregnancy and later development of chronic pain in adolescence, as well as underlying mechanisms, will also be presented. Implications for tailored, integrated interventions will be discussed.

Early life injury can sensitize animals long term: it has been shown to produce lifetime peripheral sensitization in insects and cephalopods, and to adulthood in rodents. Injury in adulthood can likewise sensitize invertebrates long-term, producing systemically increased vigilance and readiness for defence. This is not entirely unlike the anticipation of threat, overinterpretation of threat and high amplitude defence seen in human post-traumatic stress and in chronic pain. But the translation cannot be so simply made, because in invertebrates this state is adaptive, and contributes directly to better survival, whereas in humans and rodents it does not appear to be associated with any benefits, and in humans is likely associated with earlier mortality. This talk will review the evidence and take an evolutionary approach to mechanisms that in ancestral times or in the wild may confer advantages, but do not do so in laboratory rodents or modern humans. Models of psychological trauma and of pain tend to focus on proximate mechanisms, such as mutual maintenance, which are important not least for therapeutic targets, but this focus takes too little account of ultimate (evolutionary) dynamics which take a more contextual account of behavioural options and biases resulting from early experience.

Early life adversity is associated with cognitive, social and emotional impairment. We have investigated the effects of a high fat /high sugar diet, and early life stress on pain sensitivity and emotional function in the Sprague Dawley rat, using maternal separation (MS) as a model of early adversity and neglect. We will demonstrate poor diets prime the inflammatory system to be sensitized to pain and impair social and emotional functioning. In addition, when compared to control offspring, MS pups display increased anxiety-like behaviour and an altered pain response, with increased pain thresholds indicative of increased risk for chronic pain in the future. Furthermore, using advanced MR imaging, we will demonstrate that high fat/high sugar diets and MS alter structural maturation of the brain, and that the effects of MS and poor diet are cumulative; both within the brain and on pain processing and socio-emotional function.