Dennis Boye Larsen

Atrial fibrillation (AF) causes debilitating symptoms in some patients, whereas others remain asymptomatic; the biological basis remains unclear. In this prospective case–control study, we investigated whether circulating biomarkers were associated with symptom burden, differed between patients with symptomatic AF and controls, and differed between samples collected before catheter ablation and on the first post-procedural day. We enrolled 100 patients undergoing first-time AF ablation and 100 age- and sex-matched controls; one patient with AF was excluded because of compromised blood samples. Symptoms were assessed using the AF6 questionnaire and EHRA score. Ninety-two proteins were measured using the Olink Target 96 Inflammation panel, and six additional biomarkers were analysed locally. The median AF6 was 23 (IQR 14–32), and 46% had modified EHRA score III. No statistically significant biomarker–symptom associations were detected after Bonferroni correction. In age- and sex-adjusted comparisons, 12 biomarkers differed between patients with AF and controls, including higher NT-proBNP, CCL20, and CXCL10, and lower FGF-19. On the first post-procedural day, 51 biomarkers differed significantly from pre-procedural levels, with the largest increases observed for hs-TnI, IL-6, and hs-CRP. These findings demonstrate biomarker differences between AF patients and controls and an acute post-procedural response consistent with myocardial injury and inflammation. Clinical trial registration: ClinicalTrials.gov NCT05201989 09/01/2022.

Background: Peak alpha frequency (PAF), the dominant frequency in the alpha band (8–12 Hz), has been proposed as a biomarker of pain sensitivity, but mixed findings may reflect broad sensory and cognitive influences on PAF. Operant conditioning can modulate pain perception and related brain activity, but its effect on PAF has not been explored. This study investigated if PAF was lower in the context of punishment compared to PAF in the context of reward and whether these contexts differentially modulate PAF when pain intensity is held constant. Methods: Twenty‐nine healthy participants performed an auditory task while receiving painful pressure stimuli within a reward and punishment context, achieved via feedback on response correctness followed by a consequential change in pressure (maintained pressure with relief and maintained pressure with increase). Electroencephalography was recorded continuously, and PAF was extracted from frontal, central, parietal, and global regions of interest. Results: PAF was significantly lower after an incorrect response in the reward context, compared to a correct response in the punishment context, despite matched pain intensity. A more consistent finding was that PAF was lower following an incorrect response in the punishment context (increased pain) compared to a correct response in the same context (maintained pain). Conclusions: These findings suggest that PAF is modulated by ongoing pain intensity within a fixed motivational context, while evidence for context‐specific effects (reward vs. punishment) remains preliminary and warrants replication. Significance Statement: This study introduces a paradigm in which task performance determined whether pressure pain increased or decreased, to test whether context shapes peak alpha frequency (PAF) independently of pain intensity. Lower PAF was observed when pain increased, suggesting that PAF tracks pain intensity when context is held constant. A preliminary, cross‐context difference in PAF at matched pain intensities warrants replication in an adequately powered sample.

Chronic postoperative pain following total joint replacement (TJA) is a substantial clinical problem, and poor sleep may affect predictive factors for postoperative pain, such as pain catastrophizing. However, the magnitude of these associations is currently unknown. This exploratory study investigated (1) the relationship between preoperative sleep quality, clinical pain intensity, pain catastrophizing, anxiety, and depression and (2) their associations with chronic postoperative pain following TJA. This secondary analysis from a larger randomized controlled trial included rest pain intensity (preoperative and 12 months postoperative; visual analogue scale, VAS), preoperative Pittsburgh Sleep Quality Index (PSQI), Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS) data from 74 knee and 89 hip osteoarthritis (OA) patients scheduled for TJA. Poor sleepers were identified based on preoperative PSQI scores higher than 5. Poor sleepers demonstrated higher preoperative VAS, pain catastrophizing, anxiety, and depression compared with good sleepers (all p < 0.003). Preoperative PSQI (β = 0.23, p = 0.006), PCS (β = 0.44, p < 0.005), and anxiety (β = 0.18, p = 0.036) were independent factors for preoperative VAS. Preoperative VAS (β = 0.32, p < 0.005), but not preoperative sleep quality (β = −0.06, p = 0.5), was an independent factor for postoperative VAS. The OA patients reporting poor preoperative sleep quality show higher preoperative pain, pain catastrophizing, anxiety, and depression. High preoperative pain intensity, but not poor sleep quality, was associated with higher chronic postoperative pain intensity. Future studies are encouraged to explore associations between sleep and chronic postoperative pain.

Kelun Wang, Dennis Boye Larsen, Silvia Ambite-Quesada, Yuan Zhang, Huilin Liu, César Fernández-de-las-Peñas, Lars Arendt-Nielsen. J Acupunct Meridian Stud 2021;14:157-66. https://doi.org/10.51507/j.jams.2021.14.4.157

Homeostatic plasticity complements synaptic plasticity by stabilising neural activity within a physiological range. In humans, homeostatic plasticity is investigated using two blocks of non‐invasive brain stimulation (NIBS) with an interval without stimulation between blocks. The aim of this systematic review and meta‐analysis was to investigate the effect of homeostatic plasticity induction protocols on motor evoked potentials (MEP) in healthy participants. Four databases were searched (Medline, Scopus, Embase and Cochrane library). Studies describing the application of two blocks of NIBS of the primary motor cortex with an interval of no stimulation between blocks reporting changes in corticospinal excitability by MEP amplitude were included. Thirty‐seven reports with 55 experiments (700 participants) were included. Study quality was considered poor overall, with heterogeneity in study size, sample and designs. Two blocks of excitatory stimulation at the primary motor cortex produced a homeostatic response (decreased MEP) between 0 and 30 min post‐protocols, when compared with a single stimulation block. Two blocks of inhibitory stimulation at the primary motor cortex using interval duration of 10 min or less produced a homeostatic response (increased MEP) between 0 and 30 min post‐protocols, when compared with a single stimulation block. There were no differences in MEPs when compared with baseline MEPs. In conclusion, homeostatic plasticity induction using two blocks of NIBS with an interval of 10 min or less without stimulation between blocks produces a homeostatic response up to 30 min post‐protocol. Improvements in participant selection, sample sizes and protocols of NIBS techniques are needed.

Background: The underlying mechanisms for shoulder pain (SP) are still widely unknown. Previous reviews have reported signs of altered pain processing in SP measured with quantitative sensory testing (QST). Evidence suggests that QST might hold predictive value for SP after an intervention, yet it is not known whether QST profiles can be modulated in response to different treatments. Therefore, this systematic review and meta-analysis aimed to assess whether QST parameters can be modified by interventions for patients with SP. Methods: Three databases were searched to identify eligible studies. Eligible studies had a prospective design, with at least one QST variable as an outcome in conjunction with an intervention measured before and after the intervention. Studies that involved SP caused by spinal or brain injury and studies looking at combined chronic neck pain and SP were excluded. Results: Nineteen studies investigating SP were eligible for inclusion in this review. Pressure pain threshold (PPT) was the most frequently used QST parameter to investigate local and widespread hyperalgesia. A meta-analysis was performed on data from 10 studies with a total of 16 interventions. Results demonstrated an overall acute effect (<24 hours after intervention) of interventions in favor of local decreased pain sensitivity and remote decreased pain sensitivity when PPTs before and after interventions were compared. Conclusions: This study demonstrates that interventions such as exercise and manual therapy can modulate PPTs acutely, both locally and remotely, in patients with SP. Further research investigating the acute and long-term modulatory ability of these interventions on other QST parameters is needed in patients with SP.

Objectives: Approximately 20% of knee osteoarthritis patients undergoing total knee arthroplasty (TKA) report chronic postoperative pain. Studies suggest that preoperative variables such as impaired descending pain control, catastrophizing, function, and neuropathic pain–like symptoms may predict postoperative pain 12 months after TKA, but the combined prediction value of these factors has not been tested. The current prospective cohort study aimed to combine preoperative risk factors to investigate the predictive value for postoperative pain 12 months after TKA.Design: Prospective cohort with follow-up 12 months after surgery.Patients: A consecutive sample of 131 knee osteoarthritis patients undergoing TKA.Methods: Pain intensity, Pain Catastrophizing Scale (PCS) scores, PainDETECT Questionnaire scores, conditioned pain modulation (CPM), and Oxford Knee Score (OKS) were obtained before and 12 months after TKA.Results: TKA improved pain (P < 0.001), PCS scores (P < 0.001), PainDETECT Questionnaire scores (P < 0.001), and OKSs (P < 0.001). Preoperative pain correlated with preoperative PCS scores (r = 0.38, P < 0.001), PainDETECT scores (r = 0.53, P < 0.001), and OKSs (r = –0.25, P = 0.001). Preoperative PainDETECT scores were associated with preoperative PCS scores (r = 0.53, P < 0.001) and OKSs (r = –0.25, P = 0.002). Higher postoperative pain was correlated with high preoperative pain (r = 0.424, P < 0.001), PCS scores (r = 0.33, P < 0.001), PainDETECT scores (r = 0.298, P = 0.001), and lower CPM (r = –0.18, P = 0.04). The combination of preoperative pain, PCS score, and CPM explained 20.5% of variance in follow-up pain. PCS scores had a significant effect on pain trajectory when accounting for patient variance (t = 14.41, P < 0.0005).Conclusion: The combination of high preoperative clinical pain intensity, high levels of pain catastrophizing thoughts, and impaired CPM may predict long-term postoperative pain 12 months after surgery.

Studies have suggested that quantitative sensory testing (QST) might hold a predictive value for the development of chronic postoperative pain and the response to pharmacological interventions. This review systematically summarizes the current evidence on the predictive value of QST for chronic postoperative pain and the effect of pharmacological interventions. The main outcome measures were posttreatment pain intensity, pain relief, presence of moderate-to-severe postoperative pain, responders of 30% and 50% pain relief, or validated questionnaires on pain and disability. A systematic search of MEDLINE and EMBASE yielded 25 studies on surgical interventions and 11 on pharmacological interventions. Seventeen surgical and 11 pharmacological studies reported an association between preoperative or pretreatment QST and chronic postoperative pain or analgesic effect. The most commonly assessed QST modalities were pressure stimuli (17 studies), temporal summation of pain (TSP, 14 studies), and conditioned pain modulation (CPM, 16 studies). Of those, the dynamic QST parameters TSP (50%) and CPM (44%) were most frequently associated with chronic postoperative pain and analgesic effects. A large heterogeneity in methods for assessing TSP (n = 4) and CPM (n = 7) was found. Overall, most studies demonstrated low-to-moderate levels of risk of bias in study design, attrition, prognostic factors, outcome, and statistical analyses. This systematic review demonstrates that TSP and CPM show the most consistent predictive values for chronic postoperative pain and analgesic effect, but the heterogeneous methodologies reduce the generalizability and hence call for methodological guidelines.