Gwendoline Arendse

Acute pain in hospitalised patients is common, yet African data are scarce. We conducted a prospective point-prevalence study of hospitalised adult patients across Africa to determine acute pain prevalence and severity and investigate associations of pain with critical illness and 7-day mortality. On a single day, investigators assessed patients' worst pain in the preceding 24 hours using a 0 to 10 visual-numerical scale and recorded vital signs. Critical illness was defined as ≥1 vital sign out of range, in line with an international consensus definition. In-hospital mortality was assessed at day 7. Data are presented as median [interquartile range], n (%), and odds ratios with 95% confidence intervals. Between September and December 2023, 19,438 patients from 180 hospitals in 22 African nations were included (age 40 [29; 59] years; 10,874 [56%] female). Pain prevalence [95% CI] was 67.9% [67.9-68.5], with 2795 (14.4%) patients reporting severe pain (≥7/10). Pain was more common among patients admitted for emergency or trauma care and in surgical and high-care wards. Pain severity did not differ meaningfully between sexes. There was no evidence of an association between pain severity and critical illness; however, increasing pain severity was associated with a higher likelihood of 7-day mortality. These findings are comparable to data from high-income countries despite substantial differences in healthcare resources, suggesting that acute pain remains a persistent and underaddressed problem globally. This study provides the first large-scale evidence of acute pain burden in African hospitals and lays a foundation for future research aimed at comprehensively characterising in-hospital pain.

Objective: There is a bidirectional relationship between emotional distress and pain. However, this relationship is understudied in people with HIV in low-resource settings. This study sought to describe the temporal relationship between emotional distress and pain in people with HIV. Design: Longitudinal observational study. Methods: Participants with virally suppressed HIV, reporting either no pain or persistent pain at baseline, provided weekly remote ratings of distress, worst pain, and average pain using 0-10 visual analogue scales. Within-individual fluctuations in distress and pain were visualised over time. Group-level correlations were determined using Spearman’s correlation tests. Cumulative link mixed models assessed whether distress and pain each predicted the other in the following week. Results: 72 participants provided responses over 49 weeks. The participants had a median (IQR) age of 43 (37-51) years, 63% (n=45) were unemployed and most were females (n=51;71%). Distress and pain fluctuated concurrently within individuals: distress was positively correlated with worst pain (ρ=0.66, 95% CI= 0.60-0.72, p<0.001) and average pain (ρ=0.70, 95% CI=0.64-0.75, p<0.001) intensity within the same week. Worst pain (OR=1.42, 95% CI=1.17-1.71, p<0.001) and average pain (OR=1.43, 95% CI=1.20-1.71, p<0.001) intensity both predicted distress in the next week. Distress predicted worst pain intensity (OR=1.25, 95% CI=1.07-1.46, p=0.023) but not average pain intensity (OR=1.19, 95% CI=1.01-1.40, p=0.152) in the next week. Conclusions: The temporal relationship between distress and worst pain intensity was bidirectional, whereas distress did not temporally predict average pain intensity. Both pain and emotional distress should receive attention from HIV research and clinical care in low-resource settings.

Psychological distress predicts the onset and worsening of persistent pain, but the mechanisms that underpin this influence are poorly understood. Proinflammatory signalling is a plausible link, given its known connections to distress, pain, and neural upregulation. Sustained distress may prime the inflammatory system to respond more strongly to a phasic noxious challenge, supporting neuroimmune upregulation of central nociceptive signalling and persistent pain. This cross-sectional study tested the hypotheses that in vitro endotoxin-provoked expression of typically proinflammatory cytokines (IL1β, IL6) is a partial mediator between distress and persistent pain, and that it is associated with experimentally induced secondary hyperalgesia, in people with suppressed HIV. Study participants were 99 adults (mean [range] age: 43 [28-64 y/o; 72 females]) with either no pain (n = 54) or persistent pain (n = 45), mostly of black South African ethnicity, low socio-economic status, and with high social support. The results replicated previous reports that distress is associated with persistent pain status and pain severity, and distress was associated with the anatomical extent of pain. However, distress was not associated with provoked cytokine expression, nor was provoked cytokine expression associated with secondary hyperalgesia. The conflict between our findings and prior evidence could reflect the influence of differentially trained immune systems or a more complex relationship arising from diverse psychoneuroimmunological interactions in this sample. This sample's combination of HIV status, African genetic ancestry, financial impoverishment, and rich social interconnectedness is poorly represented in current research and provides an opportunity to deepen insight into psychoneuroimmunological interactions in persistent pain.

Pain and symptoms of depression and anxiety (here, ‘psychological distress’) are frequently reported by people with HIV. Although pain is widely acknowledged to contribute to distress, distress may also contribute to pain and its persistence. Facilitation of nociceptive signalling is one pathway by which distress could exacerbate pain. The current study investigated the relationships between symptoms of depression and anxiety, secondary hyperalgesia (SH), and persistent pain in people with HIV, reporting pain (n=19) or no pain (n=26). We hypothesised that self-reported distress would be positively associated with the surface area (primary measure) and magnitude (secondary measure) of induced SH, and that participants reporting persistent pain would display greater induced SH than those reporting no pain. We found that distress was positively associated with the surface area (p=0.02) and the magnitude (p=0.01) of induced SH. However, participants with persistent pain showed no difference in the surface area of SH compared to pain-free participants (p=0.87), and those with pain displayed a marginally lower magnitude of SH (p=0.05). These findings position SH as a potentially useful mechanistic outcome for interventions that aim to address pain by reducing symptoms of depression and anxiety. Perspective: Symptoms of depression and anxiety were positively associated with induced secondary hyperalgesia in people with suppressed HIV.

Psychological distress predicts the onset and worsening of persistent pain, but the mechanisms that underpin this influence are poorly understood. Pro-inflammatory signalling is a plausible mechanistic link, given its known connections to distress, pain, and neural upregulation. Sustained distress may prime the inflammatory system to respond more strongly to a phasic noxious challenge, supporting neuroimmune upregulation of central nociceptive signalling and persistent pain. This cross-sectional study tested the hypotheses that in vitro endotoxin-provoked expression of typically pro-inflammatory cytokines (IL1β, IL6) is a partial mediator between distress and persistent pain, and that it is associated with the secondary hyperalgesia response to an experimental noxious challenge, in people with suppressed HIV. Study participants were 99 adults (mean (range) age: 43(28-64y/o; 72 females) with either no pain (n=54) or persistent pain (n=45), mostly of black South African ethnicity, low socio-economic status, and with high social support. The results replicated previous reports that distress is associated with persistent pain status and pain severity, and also showed an association between distress and the anatomical extent of pain. However, distress was not associated with provoked cytokine expression, nor was provoked cytokine expression associated with secondary hyperalgesia. The conflict between our findings and the evidence on which our hypotheses were based could reflect masking of an effect by differentially trained immune systems or a more complex relationship arising from diverse psychoneuroimmunological interactions in this sample. Our sample’s combination of HIV status, African genetic ancestry, financial impoverishment, and rich social interconnectedness is poorly represented in current research and represents an opportunity to deepen insight into psychoneuroimmunological interactions related to distress and persistent pain.