ABSTRACT Background Adverse childhood experiences (ACEs) are associated with poor health in adulthood and may predispose individuals to anxiety‐related problems and somatic morbidity. However, their role in persistent pain is not fully understood. This study assessed several factors that may link ACEs with persistent pain and offer possible treatment targets. Methods This cross‐sectional study included two cohorts of patients attending tertiary pain care (total n = 644). We examined associations between ACEs, health‐related quality of life (HRQoL), comorbid conditions, pain‐related measures and psychological factors, including perceived injustice related to pain. Results Increases in the number of ACEs from two to three and from five to six were associated with lower HRQoL and more comorbid conditions. Medium ACE burden (3–5 ACEs) associated with more depression and other psychiatric comorbidities than low ACE burden (0–2 ACEs) (34.5% vs. 22.9%, p < 0.05; 12.2% vs. 3.3%, p < 0.05, respectively). High ACE burden (≥ 6 ACEs) associated also with more asthma (29.3% vs. 13.7%, p < 0.05). ACEs were associated with all anxiety‐ and distress‐related factors, correlations being relevant with depression ( r = 0.26), trait anxiety ( r = 0.25) and worry ( r = 0.24). Among the pain‐related outcomes, only pain interference was significantly associated with ACEs ( r = 0.13), and this association was statistically fully mediated by injustice perceptions. Conclusions ACE burden was associated with reduced HRQoL, psychological distress and pain interference. Perceived injustice mediated the association between ACEs and pain interference, possibly representing a treatment target for patients with pain and high ACE burden. Significance Statement This study shows that patients treated in tertiary pain care report a high number of ACEs, stress‐ and anxiety‐related processes and perceptions of injustice, which may contribute to pain persistence and may offer potential targets for treatment.
ABSTRACT Background Monoamine reuptake inhibitors are evidenced first‐line treatments of peripheral neuropathic pain. The aim was to investigate if bupropion, a drug that specifically inhibits neuronal noradrenaline and dopamine reuptake, relieves neuropathic pain and if a potential effect depends on status of conditioned pain modulation (CPM) and sensory phenotype (irritable vs. non‐irritable nociceptor). Method Study design was randomized, double‐blind, placebo‐controlled, and cross‐over. Patients with peripheral neuropathic pain were treated with bupropion and placebo in a random order, with treatment periods lasting 6 weeks preceded by a 1‐week baseline. Change in daily average pain was the primary outcome. Other outcomes included pain relief and 30% and 50% pain reduction. Results 67 patients were randomized and included in the analysis. The mean daily average pain changed from NRS 6.4 to 5.5 after bupropion treatment with an average effect as compared with placebo of −0.5 (95% CI −0.8 to −0.1, p = 0.005). No relation was found between response to treatment and efficiency of CPM or sensory phenotype. There was no significant effect on the pain relief scale. A 30% and 50% pain reduction was found in 10 and 6 patients respectively with a NNT for 50% pain reduction of 15. Bupropion was well tolerated. Conclusion Bupropion had a pain‐relieving effect independent of CPM efficiency and sensory phenotype. NNT for 50% pain reduction was higher than reported for first‐line treatments, but bupropion treatment may still be an option in patients with insufficient response or intolerable side effects on such treatments. Significance Statement This study finds a modest pain‐relieving effect of bupropion on peripheral neuropathic pain independent of function of conditioned pain modulation. Bupropion could be an alternative treatment for patients with a lack of effect or intolerable side effects to first‐choice treatments of peripheral neuropathic pain. Further, larger studies are needed to determine optimal dosage. Trial Registration: The study is registered with the EU clinical trials Register (EudraCT 2019‐000243‐27) on March 15th 2019. The study is approved by the Ethical Committee of the Region of Southern Denmark (also included approval for Regions of Central Denmark; no. S‐20190010) and the Danish Medicine Agency (no. 2019012986) and is registered with the Danish Data Protection Agency (via the Region of Southern Denmark's internal notification; no. 19/17111).
ABSTRACT Background Research has indicated that individuals experiencing chronic pain differ in their ability to sense and interpret signals arising from inside the body, termed interoception. It is unclear whether differences in interoception exist for those with endometriosis, a common condition where pain is a major symptom. Methods This study aimed to investigate whether interoceptive beliefs are altered in individuals with a diagnosis of endometriosis compared to those without, and whether pain experienced by those with endometriosis predicted interoceptive beliefs. Interoceptive beliefs were assessed in 247 participants with endometriosis and 98 participants without the condition. Those with endometriosis also reported their experience of dysmenorrhea, dyspareunia, dyschezia, and chronic pelvic pain. Results Individuals with endometriosis reported that they noticed more internal signals but had reduced trust in these signals and were more worried by them. They also reported that they try to distract themselves from internal sensations more than those without endometriosis. Increased pain intensity predicted higher scores in one facet of interoceptive beliefs, such that higher levels of pain were associated with higher awareness of internal sensations in individuals with endometriosis. Conclusions These results indicate that those with endometriosis differ in their interoceptive beliefs and that these differences may be influenced by their pain experience. Given these findings largely align with changes observed in other conditions marked by pain, it is possible that interoceptive changes may represent a transdiagnostic characteristic across individuals experiencing pain. Significance This study addresses previously conflicted findings in the literature, providing a clearer picture of the changes in interoceptive beliefs present in people with endometriosis. Developing a stronger understanding of interoceptive functioning in this unique population may lead to opportunities to develop stronger interventions targeting bodily sensations in pain management in those with the condition.
Background Representation of pain areas offers a spatial dimension of pain perception, yet it has rarely been used in the context of visceral pain. This experimental study examined spatial patterns of acute visceral and somatic pain and their recall. Methods Healthy volunteers (N = 49, 30 females) underwent calibrated rectal distension (visceral pain) and cutaneous heat stimulation on the abdomen (somatic pain), and drew modality-specific pain areas on standardised body maps immediately after stimulation and one week later. Drawings were digitised and quantified, distinguishing local from referred pain, defined as pain area separated from local site. Pain intensity and unpleasantness were assessed with visual analogue scales, psychological traits and states via questionnaires. Results Rectal distension induced larger and more diffuse areas than heat pain (p < 0.001). Pain areas were highly reproducible after one week (p < 0.001). Referred visceral pain was reported by 67% of participants, predominantly in the anterior abdomen, whereas somatic pain remained localised. Total pain areas were unrelated to pain intensity or unpleasantness. However, participants with referred visceral pain had higher trait anxiety (p = 0.011), while greater referred visceral pain extent was associated with higher pain intensity (p = 0.012). Bayesian analyses identified extraversion and behavioural inhibition as predictors of visceral pain area. Conclusion Visceral and somatic pain showed distinct, reliably recalled spatial representations. Visceral pain was more extensive and diffuse. Its association with personality traits suggests that spatial pain representations reflect stable, trait-like characteristics, highlighting the value of body maps as complementary tool for characterising interoceptive pain in experimental and clinical research. Significance Statement Visceral pain evokes a broader and more diffuse spatial representation than somatic pain, which is reliably recalled and shaped by psychological traits. Body maps capture features such as referred pain that are not reflected by intensity ratings alone. Visceral pain was predicted by personality trait factors, while referred pain extent was linked to pain intensity. These findings support modality-specific body maps as a mechanism-informed tool for stratifying visceral interoceptive pain in research and clinical contexts.
Background Fatigue frequently co-occurs with chronic pain, yet how its individual dimensions relate to pain characteristics in chronic spinal pain remains unclear. We investigated the relationships between pain severity, pain duration and multidimensional fatigue and compared fatigue and quality of life across activity pattern subgroups. Methods This cross-sectional study included 109 individuals (mean age 38.23 +/- 13.19 years) with chronic spinal pain. Pain severity was assessed with the Numerical Rating Scale (NRS), fatigue with the Multidimensional Fatigue Inventory (MFI-20), activity patterns with the Patterns of Activity Measure-Pain (POAM-P) and quality of life with the World Health Organization Quality of Life Scale Short Form (WHOQOL-BREF). Results All significant correlations were in the very weak to weak range (rho <= 0.41). General and physical fatigue, reduced motivation and MFI-20 total scores correlated weakly with pain parameters (p < 0.05). Mental fatigue correlated with resting (rho = 0.271) and night pain (rho = 0.220) but not with activity pain or pain duration; reduced activity showed a comparable pattern. The general health domain correlated negatively with pain severity and duration (p < 0.05). Participants were categorized as avoidance (n = 40), overdoing (n = 51), or pacing (n = 18). The avoidance group showed higher reduced activity scores; this difference remained significant in Bonferroni-corrected pairwise comparisons (p = 0.001) but, as the only significant finding among fifteen subgroup comparisons, warrants cautious interpretation. Conclusions Multiple dimensions of fatigue show weak associations with chronic spinal pain. Mental fatigue and reduced activity correlated with rest and night pain but not activity pain, a pattern not specific to the cognitive dimension. Incorporating pattern-specific approaches into clinical management may prove beneficial. Significance Statement This study examined multiple dimensions of fatigue in chronic spinal pain within the framework of the avoidance-endurance model. Mental fatigue and reduced activity showed comparable weak associations with resting and night pain, but not with activity pain, indicating that this pattern is not specific to the cognitive dimension. Differences between activity pattern subgroups were limited. The findings support assessing fatigue multidimensionally and highlight the need for larger studies examining fatigue across activity-related subgroups.
