The Development of Adolescent Chronic Pain following Traumatic Brain Injury and Surgery: The Role of Diet and Early Life Stress

Abstract

Pain is evolutionarily necessary for survival in that it reduces tissue damage by signaling the body to respond to a harmful stimulus. However, in many circumstances, acute pain becomes chronic, and this is often dysfunctional. Adolescent chronic pain is a growing epidemic with an unknown etiology and limited effective treatment options. Given that the relationship between acute pain and chronic pain is not straightforward, there is a need to better understand the factors that contribute to the chronification of pain. Since early life factors are critical to a variety of outcomes in the developmental and adolescent periods, they pose promise as potential mechanisms that may underlie the transition from acute to chronic pain. This review examines two early life factors: poor diet and adverse childhood experiences (ACEs); they may increase susceptibility to the development of chronic pain following surgical procedures or traumatic brain injury (TBI). Beyond their high prevalence, surgical procedures and TBI are ideal models to prospectively understand mechanisms underlying the transition from acute to chronic pain. Common themes that emerged from the examination of poor diet and ACEs as mechanisms underlying this transition included: prolonged inflammation and microglia activation leading to sensitization of the pain system, and stressinduced alterations to hypothalamic-pituitary-adrenal axis function, where cortisol is likely playing a role in the development of chronic pain. These areas provide promising targets for interventions, the development of diagnostic biomarkers, and suggest that biological treatment strategies should focus on regulating the neuroinflammatory and stress responses in an effort to modulate and prevent the development of chronic pain.

Changes of serum uric acid level during acute gout flare and related factors

“…A previous study indicated that acute monoarthritis could induce the activation of the hypothalamic–pituitary–adrenal (HPA) axis, leading to increased expression levels of related genes and concurrent with the increase in plasma CORT ( 16 ). Prolonged inflammation would sensitize the pain system and HPA axis, where cortisol likely contributes to pain development ( 17 ). IL-6 and TNF-α share HPA-activating activity, although they are less potent and less effective than IL-1 ( 18 ).…”

The role of the stress system in recovery after traumatic brain injury: A tribute to Bruce S. McEwen

“…For example, among pediatric patients, post-concussive depression is rarely reported with mild (compared to more severe) TBI, however pediatric mild TBI patients who do report persistent depressive symptoms are more likely to have experienced ELS ( Smyth et al, 2014 ). Adverse childhood experiences are also associated with an exaggerated immune response to pain and increased pain sensitivity after mild TBI in adolescents ( Salberg et al, 2020 ), and the subjective experience of pain is a strong predictor of the development of depressive symptoms. ELS is also a risk factor for TBI in adulthood.…”

The Neurobiological Links between Stress and Traumatic Brain Injury: A Review of Research to Date

“…These adaptations occur during critical windows of development because of genetics and epigenetics. This concept is named programming theory [ 161 ]. If prenatal or early life environmental conditions do not match those later in life, this programming may be maladaptive and predispose individuals to disease [ 161 ].…”

“…This concept is named programming theory [ 161 ]. If prenatal or early life environmental conditions do not match those later in life, this programming may be maladaptive and predispose individuals to disease [ 161 ]. Therefore, early life stress factors are crucial in explaining the different outcomes after TBI.…”