Psychological stress in early life as a predisposing factor for the development of chronic pain: Clinical and preclinical evidence and neurobiological mechanisms

Abstract

A wealth of research over the past 2 decades has expanded our understanding of the impact of early-life adversity on physiological function and, consequently, health and wellbeing in later life. Early-life adversity increases the risk of developing a number of disorders, such as chronic pain, fibromyalgia, and irritable bowel syndrome. Although much of the research has examined the impact of physical maltreatment, an increasing number of studies have been published over the past few years examining the effect of childhood psychological stress and trauma on the development of various types of chronic pain conditions. We review the clinical and preclinical data examining the link among early-life psychological stress, altered nociceptive behavior, and chronic pain in later life. Evidence supporting a role for certain key neurobiological substrates, including the hypothalamic-pituitary-adrenal axis; monoaminergic, opioidergic, endocannabinoid and immune systems; and epigenetic mechanisms in the association between early-life psychological stress and chronic pain, is provided. Greater understanding of the impact of early-life stress may inform the development of personalized treatments for chronic pain in later life and strategies to prevent its onset in susceptible individuals. © 2016 Wiley Periodicals, Inc.

Opioids Resistance in Chronic Pain Management

“…The neurobiological mechanisms underlying the relationship between early-life stress and development of chronic pain are unclear, however, clinical and preclinical data suggested a key role for some neuro-
biological substrates, e.g . the hypothalamic-pituitary-adrenal axis, neurotransmissions (monoaminergic, opioidergic, endo-
cannabinoid) and immune systems [45-47]. In this regard, Interestingly, in maternal separation, one of the most commonly used models of early-life stress, Ploj and colleagues reported altered expression of the endogenous opioids dynorphin and enkephalin in the hypothalamus, substantia nigra, amygdala, and periaqueductal gray key brain areas in the modulation of emotional and nociceptive processes [48].…”

“…Moreover, Alexander and colleagues reported that stress potentiates nerve injury-induced tactile allodynia through a mechanism involving glucocorticoids acting at glucocorticoid receptors and glutamate receptor-mediated extracellular signal-regulated kinase (ERK) activation in dorsal horn neurons suggesting that these pathways converge to cause central sensitization [42]. Epigenetic alterations may also represent one of the key mechanisms underlying the development of chronic pain in later life [43, 47, 49-51]. …”

An Integrated Model of Chronic Whiplash-Associated Disorder

“…These variables include prevailing cultural beliefs about the experience and expression of pain and suffering, 10,36,38,78 the medicolegal context within which the injury occurs, 21,37,85 the quality of social support, 90 and other life stressors (both recent and earlier in life). 15 Importantly, the extent to which these factors are either resiliencies or vulnerabilities likely varies by context, such that they may be a vulnerability under one condition and protective under another. 1 Take, for example, auto insurance coverage as a factor: adequate financial means to afford appropriate insurance coverage provided (or perceived to be provided) under a supportive client-insurer relationship may facilitate the patient's resumption of a satisfactory life trajectory.…”

Translational studies identify long-term impact of prior neonatal pain experience

“…[185] However, ELS can be difficult to quantify and many studies do not control for the nature, frequency or duration of exposure. [27] iii) type of ELS. This can influence the brain region affected and the behavioral outcome.…”

“…Increased inhibition is reflected by either an increased threshold (if utilizing a protocol with a variable test stimulus) or reduced pain intensity (fixed test stimulus). [101; 142; 156; 222] In preterm born (24)(25)(26)(27)(28)(29)(30)(31)(32) weeks GA) children, CPM was enhanced in those with fewer painful procedures in NICU (n=6), but absent in a 'high-pain' group (n=7) with longer NICU stay and mechanical ventilation. [72] However, this study was performed at 8-11 years of age when descending modulation is less effective, [189] and evaluation at older ages is required.…”