Background & Aims
Adverse childhood experiences (ACEs) are any potentially stressful events or environments that occur before the age of 18. They include abuse, neglect, familial challenges (e.g. parental separation), and external challenges (e.g. bullying). Such adversity in childhood is common: estimates suggest that 47% of the UK population have experienced at least one form of ACE (1). Chronic pain, pain that persists or recurs for longer than three months (2), is also common: overall adult prevalence estimates range from 19% to 44% (3–6). There is a growing body of evidence to support a dose-dependent relationship between ACEs and adult chronic pain, which is consistent in a range of different populations (7–13). However, it is less clear whether an individual’s history of ACEs should affect how their chronic pain is managed. In this review we focus on analgesic medications and assess whether exposure to ACEs alters outcomes linked to their prescription or use (analgesia-related outcomes).
Methods
We conducted a systematic review (PROSPERO: CRD42023389870), searching the following databases from inception to 26/09/2023: APA PsycNET, CINAHL Plus, Cochrane CENTRAL, Embase, MEDLINE, Scopus, and Web of Science. The search strategy included strings for ACEs, analgesia, analgesic groups, and 59 individual analgesics, to capture a range of analgesia-related outcomes. Inclusion criteria were: 1) studies examining adversity in childhood (<18 years); 2) any analgesia-related outcome in adulthood (≥18 years); 3) human studies; and 4) English language. Exclusion criteria were: 1) studies only examining adversity in adulthood; and 2) editorials, case reports, or conference abstracts. Two reviewers independently performed title/abstract screening, full text review, data extraction, and risk of bias assessment (ROBINS-E or ROB-2) using a pre-agreed template. Discrepancies were resolved by consensus discussion. Because of significant study heterogeneity, a narrative synthesis was performed.
Results
Of 7,531 identified records, 66 met inclusion criteria, involving 137,395 participants (duplicate cohorts excluded). 45 studies assessed substance misuse outcomes (opioids=44, sedatives=6). Compared to no/low ACE exposure, high ACE exposure was associated with opioid misuse (21/27 studies), severity of opioid misuse (4/4 studies), younger age at opioid initiation (7/8 studies), opioid relapse (1/1 study), and sedative misuse (4/5 studies). 12 studies assessed prescription outcomes (opioids=6, any prescription analgesia=4, sedatives=1, over-the-counter (OTC) analgesia=1). High ACE exposure was associated with any analgesic prescription (3/4 studies) and OTC analgesia (1/1 study), partially associated with opioid prescription (3/7 studies), but not associated with sedative use (0/1 study). Higher ACE exposure was also associated with medication side-effects (5/5 studies), endogenous pain signalling (2/4 studies), lifetime overdose (2/2 studies), and attempted suicide (1/1 study).
Conclusions
The published data support the hypothesis that high ACE exposure leads to poor analgesia-related outcomes like substance misuse. However, no studies assessed whether analgesic effectiveness was influenced by prior ACE exposure. Furthermore many papers in our review focused on opioid-related outcomes, which is perhaps understandable given the high profile given to the “opioid crisis” in scientific and mainstream media (14,15). It is surprising that equivalent work is not available for other high-risk analgesics. For example, no studies looked at the impact of ACEs on gabapentinoid outcomes, despite the growing recognition that gabapentinoid co-prescription is linked to increases in drug-related deaths (16,17). The findings reinforce the need to adopt trauma-informed approaches to healthcare, especially in specialties like chronic pain where the prevalence of ACEs is high (13), though progress has been disjointed (18). Further targeted research is required to address these evidence gaps.
References
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Presenting Author
Dhaneesha Senaratne
Poster Authors
Dhaneesha Senaratne
MB BChir
University of Dundee
Lead Author
Mia Koponen MSc
MSc
University of Dundee
Lead Author
Karen N. Barnett
University of Dundee
Lead Author
Blair H. Smith
University of Dundee
Lead Author
Tim G. Hales
University Of Dundee
Lead Author
Louise Marryat PhD
PhD
University of Dundee
Lead Author
Lesley A. Colvin
University of Dundee
Lead Author
Topics
- Systematic Reviews/Meta-Analysis