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17 Articles in Volume 20, Issue #3
20/20 with Dr. Suzanne Amato Nesbit: Clinical Pharmacy Roles and Disparities
A Clinician’s Guide to Treating Chronic Overuse Injuries
Adhesive Arachnoiditis: No Longer a Rare Disease
Analgesics of the Future: Cebranopadol as an Opioid Alternative
Ask the PharmD: What role do vitamin D supplements play in treating dysmenorrhea?
Behavioral Pain Medicine: Managing the Affective Components of Pain
Chronic Fatigue Syndrome: Naltrexone as an Alternative Treatment
Chronic Pain and Coronavirus
Connecting the Dots: How Adverse Childhood Experiences Predispose to Chronic Pain
Editorial: Why Are ER Opioids Out of Favor?
Fibromyalgia as a Neuropathic Pain Disorder: The Link to Small Fiber Neuropathy
How the COVID-19 Pandemic Is Transforming Pain Care
Hydroxychloroquine Use and Risk in the Management of Systemic Lupus Erythematosus
Management of Trigeminal Neuralgia in Multiple Sclerosis
Optimizing Care Using a Trauma-Informed Approach
Pediatric Pain Management: A Review of Clinical Diagnosis and Management
The Use of Low Dose Naltrexone in the Management of Chronic Pain

Connecting the Dots: How Adverse Childhood Experiences Predispose to Chronic Pain

Multiple studies worldwide have shown a dose-response relationship between traumatic events in childhood, such as abuse, neglect, or a dysfunctional home, and later development of chronic pain.
Pages 24-28

Studies worldwide have shown a relationship between traumatic events in childhood and later development of chronic pain. Inside the connections and possibilities for preventing trauma-based, adult-onset chronic pain.


Despite the narrative prevalent across some media platforms, chronic pain is not simply a symptom; nor is it a condition over-diagnosed by naïve (or nefarious) US doctors who have been influenced by manufacturers of opioid analgesics. Rather, chronic pain is a “separate condition in its own right, with its own medical condition and taxonomy.”1 Its high prevalence remains a significant public health challenge worldwide, with approximately 1 in 5 adults reporting significant chronic pain symptoms,2 and 1 in 12 reporting high-impact symptoms, which negatively affect functionality, social interaction, and economic productivity.3

Multiple studies from around the globe have shown a dose-response relationship between adverse childhood events and development of chronic pain in adulthood. (Image: iStock)

Emerging Links between ACEs and Adult-Onset Pain

Over the past three decades, an emerging understanding of the links between adverse childhood experiences (ACEs) and negative health effects in later life (see Figure 1)4 has expanded to inform our approach to patients who develop chronic pain.5 ACEs are defined as significant negative conditions or experiences in childhood (less than 18 years of age), including physical and sexual abuse, neglect, humiliation, and parental separation, divorce, or incarceration (see “Types of ACEs” below).

Multiple studies from around the globe have shown a dose-response relationship between ACEs and later development of chronic pain.6-10 The presence of such early trauma appears to confer a two- to three-fold risk of later development of chronic pain.11 In a recent large German study by Brown, et al (n=2,491),12 the largest effect sizes were found for emotional abuse. Whereas physical and/or sexual abuse tended to correlate with physical pain, emotional abuse tended to correlate with diffuse pain (a phenomenon that has been observed in other studies).13

Although depression and anxiety were increased in the patient cohort, multi-regression analysis showed an effect of ACEs on later pain scores independent of mental illness. For women, all forms of mistreatment (eg, emotional abuse, physical abuse, sexual abuse, physical neglect, and bullying) were associated with pain; for men, however, only physical and sexual abuse were significantly associated with later-life pain. Psychodynamic processes, including catastrophizing14 and anxiety,15 mediate some of the sex differences in pain perception.


It appears that catastrophizing may explain not only some of the gender differences in pain perception but racial differences as well.16 There is also biologic evidence to support that gender, far from being solely a social construct, has a profound influence on the responsiveness of the hippocampal-hypothalamic-pituitary-adrenal axis, rates of brain circuitry maturation, and neuroimmune development.17 Of course, psychodynamic and neurobiologic phenomena are connected; for instance, catastrophizing is associated with maladaptive activity in the amygdala, as well as decreased pain inhibition activity by the periaqueductal gray matter.18 These effects may help to explain differential responses of males and females to exposure to ACEs, and future development of painful conditions.

Research implicates dysregulation of the central stress response system (hypothalamic pituitary adrenal [HPA] axis) among persons with a history of childhood trauma and chronic pain.19 Indeed, the HPA axis is designed to regulate the body’s response to stress. However, in the event of significant traumatic exposures like adverse childhood experiences, this system may be chronically activated which results in increased “wear and tear” on the body. Over time, this chronic activation can affect brain development which in turn impacts learning, behaviors, and emotional functioning. Via these mechanisms, childhood trauma and ACES can result in poor physical and mental health in adulthood – things like metabolic disorders, cardiovascular disease, depression, and even chronic pain.20,21 The most extreme cases of HPA dysregulation are frequently observed among persons with post-traumatic stress disorder (PTSD). Notably, among those with increasing PTSD symptomatology, rates of musculoskeletal and other ill-defined pain conditions (eg, fibromyalgia, pelvic pain, irritable bowel) increase appreciably.22

Explaining the Correlations

Efforts to explain the correlation between ACEs and the development of chronic pain have rightly focused on the likelihood of comorbidity with depression, anxiety, and other affective illnesses. When patients have mental illness or emotional distress, they are twice as likely to develop chronic pain,23 and numerous studies have demonstrated that these factors are actually more predictive than the severity of pain in establishing pain chronicity and driving negative outcomes such as disability and healthcare costs.18 A number of psychodynamic and interpersonal factors may be in play, including catastrophization, decreased perceived overall wellness, development of a sense of an external locus of control,24 and lack of social support.25 But given the findings of the Brown study, as well as a large US study that also showed an effect of ACEs on experiences of pain independent of depression,26 it is likely that the propensity for increased sensitivity to pain is mediated not only by psychodynamic processes but also by substantive changes in the substrate and function of the brain.

For example, patients with depression exhibit neuroanatomic reorganization, neurotrophin and monoamine depletion, neuroinflammation, and endocannabinoid system perturbation.27 Regions of the brain known to be part of the neural networks involved in pain perception (eg, the anterior cingulate cortex, the amygdala, and the hippocampus) have been demonstrated to be altered by exposure to ACEs.28 These changes include hyper-responsiveness of the limbic system to threat,29 reduced limbic-prefrontal connectivity,30 and reduced hippocampal activity during pain-empathy tasks.31

In addition to these psychodynamic and neural network changes, which can lead to allostatic load,32 adverse early life experiences have also demonstrated powerful effects on later-life inflammatory processes, mediated in part by genetic predisposition or epigenetic alteration. For example, FKBP5 and CRHR1 polymorphisms can increase the risk of PTSD after abuse.33 Epigenetic changes such as DNA methylation can lead to a higher risk of pain memory, pain-related anxiety, hyperalgesia, pain exacerbation, pain persistence, pain vulnerability, and lack of analgesic response.18 In addition to directly influencing pain outcomes, genetic and epigenetic changes can increase risks for a host of metabolically-linked illnesses (eg, diabetes, heart disease), as well as affective disorders.34 This process may be best viewed as multifactorial, with genetic, gender, epigenetic, and neuropsychiatric inputs. Such “biological embedding”35 promotes a pro-inflammatory brain/body interface,36 which interacts with environmental factors to result in deleterious outcomes across biopsychosocial and spiritual domains. The increased prevalence of chronic pain in such a milieu should come as no surprise.



An ACE Quiz from ACEs Too High, a news site that reports on research and developments in epidemiology, neurobiology, and the biomedical and epigenetic consequences of toxic stress, is available at https://acestoohigh.com/got-your-ace-score/.


Tweaking Clinical Approaches

In light of the emerging model of how adverse childhood experiences influence patient outcomes, how might we best approach our patients? For starters, we should screen all of our patients who suffer from chronic pain for ACEs; a free version of the ACEs quiz is available online.37 For patients with a significant history of trauma, expressing empathy and offering a referral to a behavioral health specialist should be a minimum expectation of those providing integrative pain management. There is evidence that psychotherapeutic interventions can positively change both neurobiologic and psychodynamic correlates of chronic pain, helping patients to “unlearn” patterns of chronic pain at the level of neural networks, as well as that of subconscious and conscious responses. For example, a short study of CBT demonstrated changes in gray matter and improved functional connectivity in chronic pain patients.38 And at the level of psychological change, catastrophizing can be reduced by improving dispositional optimism, resulting in reduced pain sensitivity.39 Both CBT40 and MBSR41 have been shown to improve self-efficacy, which can, in turn, improve pain outcomes. (Driscoll provides a more-indepth approach to trauma-informed care on page 29.)

For the duration of the modern medical era, clinicians attempted to correlate objectively identifiable tissue damage with subjective patient responses expressed as pain, and to tailor therapies that corrected biomedical abnormalities in an effort to achieve positive outcomes. That failure to account for past trauma and current affective, behavioral, and cognitive maladaptive responses led to suboptimal responses of patients with chronic pain who were exposed to truncated treatments.

Biologic reductionism may sell pills and drive up numbers of invasive procedures, but it is a poor theoretical construct from which to effect positive change. When patient needs remain unmet by integrative, multidisciplinary care, they tend to seek relief along less productive pathways, both within the confines of the restrictive model (eg, with prescriptions for benzodiazepines) and without (eg, with tinctures of CBD oil).

As it turns out, things are significantly more complex than we thought for the past two centuries, and the postmodern medical model (which began with Engel42) may be better suited to the treatment of patients with chronic pain. The effect of adverse childhood experiences is a case in point, a fortiori. Human brains work better when they are allowed to develop in safe and nurturing environments, and human bodies experience less pain when they are allowed to receive input from a healthy brain. When we insist on approaching chronic pain as a purely biomedical phenomenon, and ignore its psychosocial and spiritual etiologic factors and outcome modifiers, we consign the patient to suboptimal treatment. That’s not acceptable. These were mistreated once as children; there is no excuse for history to repeat itself when they become patients. 


Editor's Note: More from Dr. Jackson on current gaps in mental health screenings in primary and specialty care in the US – and how to treat comorbid chronic pain conditions and psychiatric disorders with pain psychologist Robert Twillman – on our clinical sister site Psycom Pro.

Last updated on: May 11, 2021
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