Is Antiviral Treatment with Remdesivir at the Acute Phase of SARS-CoV-2 Infection Effective for Decreasing the Risk of Long-Lasting Post-COVID Symptoms?

The aim of this study was to investigate the effects of administrating Remdesivir at the acute COVID-19 phase on developing post-COVID symptoms in previously hospitalized COVID-19 survivors by controlling factors such as age, sex, body mass index, and vaccination status. A case-control study was performed. Hospitalized COVID-19 survivors who had received intravenous Remdesivir during the acute phase (n = 216) were matched by age, sex, body mass index, and vaccination status with survivors who did not receive antiviral treatment (n = 216). Participants were asked to self-report the presence of any post-COVID symptom (defined as a symptom that started no later than three months after infection) and whether the symptom persisted at the time of study (mean: 18.4, SD: 0.8 months). Anxiety levels (HADS-A), depressive symptoms (HADS-D), sleep quality (PSQI), and severity/disability (FIC) were also compared. The multivariate analysis revealed that administration of Remdesivir at the acute COVID-19 phase was a protective factor for long-term COVID development (OR0.401, 95%CI 0.256-0.628) and specifically for the following post-COVID symptoms: fatigue (OR0.399, 95%CI 0.270-0.590), pain (OR0.368, 95% CI 0.248-0.548), dyspnea at rest (OR0.580, 95%CI 0.361-0.933), concentration loss (OR0.368, 95%CI 0.151-0.901), memory loss (OR0.399, 95%CI 0.270-0.590), hair loss (OR0.103, 95%CI 0.052-0.207), and skin rashes (OR0.037, 95%CI 0.005-0.278). This study supports the potential protective role of intravenous administration of Remdesivir during the COVID-19 acute phase for long-lasting post-COVID symptoms in previously hospitalized COVID-19 survivors.

Analysis of opioid analgesics consumption in Africa: a longitudinal study from a 20-year continental perspective.

BACKGROUND: Opioid analgesics are essential for managing acute and chronic pain in diseases such as cancer. Inadequate opioid access remains a major public health concern in low-income regions including Africa. This study aimed to provide updated and comprehensive data on changes in opioid consumption, specifically in Africa. METHODS: This longitudinal study has updated and expanded upon the International Narcotics Control Board data obtained from 1999 to 2021, assessing opioid consumption trends across all African countries. The defined daily doses for statistical purposes (SDDD) was used to determine the changes in opioid consumption in Africa. In addition, we used sub-analyses of the data to delve into individual substances, income levels, cancer incidence, cancer mortality, and sub-regional cluster analysis (based on the language spoken) to identify possible disparities and inform further research and tailored solutions. FINDINGS: Our results indicate a persistently low and stagnant trend in opioid consumption between 2001-03 and 2019-21, from 73 SDDD (95% CI 69-77) to 55 SDDD (32-79). In-depth analysis revealed a morphine consumption increase from 735 SDDD in 1999 to 1115 SDDD in 2021. Moreover, opioid consumption was closely related to country-level income levels, with most of the low-income and lower-middle-income African countries reporting low opioid consumption. Notably, the escalating incidence and mortality rates associated with cancer in Africa indicated a misalignment with the trajectory of opioid use. Additionally, French-speaking African countries exhibited lower opioid usage than the rest of the continent, suggesting avenues for research into cultural, political, and social aspects. INTERPRETATION: In the context of global doubling in opioid consumption, Africa has shown insufficient and stagnant opioid consumption during the last 20 years. These findings underscore the need for policy reform to facilitate safe and responsible opioid access in Africa, particularly for legitimate indications such as cancer pain and palliative care. FUNDING: None. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Prognostic value of preoperative mechanical hyperalgesia and neuropathic pain qualities for postoperative pain after total knee replacement.

BACKGROUND: Total knee replacement (TKR) is the gold standard treatment for end-stage chronic osteoarthritis pain, yet many patients report chronic postoperative pain after TKR. The search for preoperative predictors for chronic postoperative pain following TKR has been studied with inconsistent findings. METHODS: This study investigates the predictive value of quantitative sensory testing (QST) and PainDETECT for postoperative pain 3, 6 and 12 months post-TKR. We assessed preoperative and postoperative (3 and 6 months) QST measures in 77 patients with knee OA (KOA) and 41 healthy controls, along with neuropathic pain scores in patients (PainDETECT). QST parameters included pressure pain pressure threshold (PPT), pain tolerance threshold (PTT), conditioned pain modulation (CPM) and temporal summation (TS) using cuff algometry, alongside mechanical hyperalgesia and temporal summation to repeated pinprick stimulation. RESULTS: Compared to healthy controls, KOA patients at baseline demonstrated hyperalgesia to pinprick stimulation at the medial knee undergoing TKR, and cuff pressure at the calf. Lower cuff algometry PTT and mechanical pinprick hyperalgesia were associated with preoperative KOA pain intensity. Moreover, preoperative pinprick pain hyperalgesia explained 25% of variance in pain intensity 12 months post-TKR and preoperative neuropathic pain scores also captured 30% and 20% of the variance in postoperative pain at 6 and 12 months respectively. A decrease in mechanical pinprick hyperalgesia from before surgery to 3 months after TKR was associated with lower postoperative pain at the 12 months post-TKR follow-up. CONCLUSION: Our findings suggest that preoperative pinprick hyperalgesia and neuropathic-like pain symptoms show predictive value for the development of chronic post-TKR pain. SIGNIFICANCE STATEMENT: This study's findings hold significant implications for chronic pain management in knee osteoarthritis patients, particularly those undergoing total knee replacement surgery (TKR). Mechanical hyperalgesia and neuropathic pain-like characteristics predict postoperative pain 1 year after TKR, emphasizing the importance of understanding pain phenotypes in OA for selecting appropriate pain management strategies. The normalization of hyperalgesia after surgery correlates with better long-term outcomes, further highlighting the therapeutic potential of addressing abnormal pain processing mechanisms pre- and post-TKR.

The polymorphism Val158Met in the COMT gene: disrupted dopamine system in fibromyalgia patients?

ABSTRACT: The single-nucleotide polymorphism (SNP) rs4680 in the catechol-O-methyltransferase gene ( COMT ) is a missense variant (Val158Met) associated with altered activity of the COMT enzyme and suggested as a predictive feature for developing some chronic pain conditions. However, there are controversial results on its role in fibromyalgia (FM). Here, the SNP Val158Met was analyzed in 294 FM patients (without comorbidities) and 209 healthy controls (without chronic pain). The concurrent impact of Val158Met genotypes and FM comorbid disorders (depression and sleep impairment) on FM risk were tested. In addition, the genotypic distribution of FM patients in relation to pain intensity was evaluated. The G allele (Val) resulted in being more represented in the FM group (57.8%) compared with the control group (48.8%; P = 0.037). Logistic regression highlighted that having the G/G (Val/Val) homozygous genotype was associated with 2 times higher risk of having FM compared with the A/A (Met/Met) carriers ( P = 0.038), whereas depression and sleep impairment increased FM risk by 12 and 8 times, respectively ( P < 0.001). However, considering only the FM patient group, the A/A homozygous genotype was significantly associated with severe pain intensity ( P = 0.007). This study highlighted associations between the SNP Val158Met and both FM and pain intensity, suggesting a link between dopaminergic dysfunction and vulnerability to chronic pain. Further studies should explore this SNP in FM patients in conjunction with COMT enzymatic activity and other symptoms connected with the dopaminergic system such as depression or sleep impairment.

Prevalence and Risk Factors of Multitype Post-COVID Pain in a Cohort of Previously Hospitalized COVID-19 Survivors: A Danish Cross-Sectional Survey.

This population-based study investigated the prevalence of de novo, multitype, post-coronavirus disease (COVID) pain and its associated risk factors in previously hospitalized coronavirus disease 2019 (COVID-19) survivors. The nationwide, cross-sectional study included a cohort of Danish residents previously hospitalized due to severe acute respiratory syndrome coronavirus-2 infection between March 2020 and December 2021. Demographic data, preexisting medical comorbidities, previous pain-related symptoms, medication use for pain management, pain intensity (4-point scale), and development of de novo, multitype, post-COVID pain were collected by a self-reported survey distributed via e-Boks (a secured national digital mail system used in Denmark to provide public information to residents). The sample comprised 4,712 previously hospitalized COVID-19 survivors (48.6% women, mean age: 60.1 ± 15.6 years). At the time of the study (21 ± 6 months after hospitalization), 18.0% (847) reported the presence of de novo, multitype, post-COVID pain, and 38.6% of any pain. A multivariate analysis revealed that female sex (Odds Ratio (OR) 1.711, 95% Confidence Interval (CI) 1.444-2.023), higher body mass index (OR 1.032, 95% CI 1.019-1.045), intensive care unit admission (OR 1.597, 95% CI 1.324-1.926), previous history of whiplash (OR 2.471, 95% CI 1.004-6.081), anxiety (OR 3.626, 95% CI 1.335-9.708), and younger age (OR .982, 95% CI .976-.987) were factors associated with development of de novo, multitype, post-COVID pain. High income (OR .635, 95% CI .494-.817) and high educational level (OR .774, 95% CI .609-.984) were protective factors. In conclusion, multitype pain as a de novo post-COVID symptom was present in 18.0% of previously hospitalized COVID-19 survivors more than 1 year after hospital discharge and as such can be considered as adding to the global burden of chronic pain. PERSPECTIVE: The study investigates the prevalence of de novo, multitype, post-COVID pain in previously hospitalized COVID-19 survivors. This article presents potential risk factors associated with developing new pain symptoms. The results will contribute to understanding the possibility of predicting postinfectious pain from COVID-19 for future analysis.

Small fibre neuropathy frequently underlies the painful long-COVID syndrome.

ABSTRACT: Approximately 10% to 20% of individuals with previous SARS-CoV-2 infection may develop long-COVID syndrome, characterized by various physical and mental health issues, including pain. Previous studies suggested an association between small fibre neuropathy and pain in long-COVID cases. In this case-control study, our aim was to identify small fibre neuropathy in patients experiencing painful long-COVID syndrome. Clinical data, quantitative sensory testing, and skin biopsies were collected from 26 selected patients with painful long-COVID syndrome. We also examined 100 individuals with past COVID-19 infection, selecting 33 patients with painless long-COVID syndrome, characterized mainly by symptoms such as brain fog and fatigue, and 30 asymptomatic post-COVID-19 controls. Demographic and clinical variables were compared among these groups. Among the 26 patients with painful long-COVID syndrome, 12 had skin biopsy and/or quantitative sensory testing abnormalities compatible with small fibre neuropathy. Demographic and clinical data did not differ across patients with small fibre neuropathy, patients with painless long-COVID syndrome, and asymptomatic post-COVID-19 controls. This case-control study showed that approximately 50% of patients experiencing painful long-COVID syndrome had small fibre neuropathy. However, in our patient cohort, this specific post-COVID-19 complication was unrelated to demographic and COVID-19 clinical variables. Approximately half of our sample of patients with painful long-COVID symptoms met diagnostic criteria for small fibre neuropathy.

Association of OPRM1 rs1799971, HTR1B rs6296 and COMT rs4680 polymorphisms with clinical phenotype among women with fibromyalgia.

To investigate the association between three selected pain polymorphisms and clinical, functional, sensory-related, psychophysical, psychological or cognitive variables in a sample of women with fibromyalgia (FMS). One hundred twenty-three (n = 123) women with FMS completed demographic (age, height, weight), clinical (years with pain, intensity of pain at rest and during daily living activities), functional (quality of life, physical function), sensory-related (sensitization-associated and neuropathic-associated symptoms), psychophysical (pressure pain thresholds), psychological (sleep quality, depressive and anxiety level) and cognitive (pain catastrophizing, kinesiophobia) variables. Those three genotypes of the OPRM1 rs1799971, HTR1B rs6296 and COMT rs4680 single nucleotide polymorphisms were obtained by polymerase chain reactions from no-stimulated whole saliva collection. No significant differences in demographic, clinical, functional, sensory-related, psychophysical, psychological and cognitive variables according to OPRM1 rs1799971, HTR1B rs6296 or COMT rs4680 genotype were identified in our sample of women with FMS. A multilevel analysis did not either reveal any significant gene-to-gene interaction between OPRM1 rs1799971 x HTR1B rs6296, OPRM1 rs1799971 x COMT rs4680 and HTR1B rs6296 x COMT rs4680 for any of the investigated outcomes. This study revealed that three single nucleotide polymorphisms, OPRM1 rs1799971, HTR1B rs6296 or COMT rs4680, mostly associated with chronic pain were not involved in phenotyping features of FMS. Potential gene-to-gene interaction and their association with clinical phenotype in women with FMS should be further investigated in future studies including large sample sizes.

Presence of SARS-CoV-2 RNA in COVID-19 survivors with post-COVID symptoms 2 years after hospitalization: The VIPER study.

The SARS-CoV-2 VIrus PERsistence (VIPER) study investigated the presence of long-lasting SARS-CoV-2 RNA in plasma, stool, urine, and nasopharyngeal samples in COVID-19 survivors. The presence of SARS-CoV-2 RNA reverse transcription polymerase chain reactions (RT-PCR) were analyzed within plasma, stool, urine, and nasopharyngeal swab samples in COVID-19 survivors with post-COVID symptoms and a comparison group of COVID-19 survivors without post-COVID symptoms matched by age, sex, body mass index and vaccination status. Participants self-reported the presence of any post-COVID symptom (defined as a symptom that started no later than 3 months after the initial infection). Fifty-seven (57.9% women, age: 51.1, standard deviation [SD]: 10.4 years) previously hospitalized COVID-19 survivors with post-COVID symptoms and 55 (56.4% women, age: 50.0, SD: 12.8 years) matched individuals who had a past SARS-CoV-2 infection without post-COVID symptoms were evaluated 27 (SD 7.5) and 26 (SD 8.7) months after hospital discharge, respectively. The presence of SARS-CoV-2 RNA was identified in three nasopharyngeal samples of patients with post-COVID symptoms (5.2%) but not in plasma, stool, or urine samples. Thus, SARS-CoV-2 RNA was not identified in any sample of survivors without post-COVID symptoms. The most prevalent post-COVID symptoms consisted of fatigue (93%), dyspnea, and pain (both, 87.7%). This study did not find SARS-CoV-2 RNA in plasma, stool, or urine samples, 2 years after the infection. A prevalence of 5.2% of SARS-CoV-2 RNA in nasopharyngeal samples, suggesting a potential active or recent reinfection, was found in patients with post-COVID symptoms. These results do not support the association between SARS-CoV-2 RNA in plasma, stool, urine, or nasopharyngeal swab samples and post-COVID symptomatology in the recruited population.

Exercise and Pain Neuroscience Education for Patients With Chronic Pain After Total Knee Arthroplasty: A Randomized Clinical Trial.

Importance: Up to 20% of patients develop chronic pain after total knee arthroplasty (TKA), yet there is a scarcity of effective interventions for this population. Objective: To evaluate whether neuromuscular exercise and pain neuroscience education were superior to pain neuroscience education alone for patients with chronic pain after TKA. Design, Setting, and Participants: A superiority randomized clinical trial was conducted at 3 outpatient clinics at Aalborg University Hospital in Denmark. Participants with moderate-to-severe average daily pain intensity and no signs of prosthesis failure at least 1 year after primary TKA were included. Participant recruitment was initiated on April 12, 2019, and completed on October 31, 2022. The 12-month follow-up was completed on March 21, 2023. Interventions: The study included 24 sessions of supervised neuromuscular exercise (2 sessions per week for 12 weeks) and 2 total sessions of pain neuroscience education (6 weeks between each session) or the same pain neuroscience education sessions alone. The interventions were delivered in groups of 2 to 4 participants. Main Outcomes and Measures: The primary outcome was change from baseline to 12 months using the mean score of the Knee Injury and Osteoarthritis Outcome Score, covering the 4 subscales pain, symptoms, activity of daily living, and knee-related quality of life (KOOS4; scores range from 0 to 100, with higher scores indicating better outcomes). The outcome assessors and statistician were blinded. All randomized participants were included in the intention-to-treat analysis. Results: Among the 69 participants (median age, 67.2 years [IQR, 61.2-71.9 years]; 40 female [58%]) included in the study, 36 were randomly assigned to the neuromuscular exercise and pain neuroscience education group, and 33 to the pain neuroscience education-alone group. The intention-to-treat analysis showed no between-group difference in change from baseline to 12 months for the KOOS4 (7.46 [95% CI, 3.04-11.89] vs 8.65 [95% CI, 4.67-12.63] points; mean difference, -1.33 [95% CI, -7.59 to 4.92]; P = .68). Among the 46 participants who participated in the 12-month assessment in the 2 groups, 16 (34.8%) experienced a clinically important improvement (a difference of ≥10 points on the KOOS4) with no between-group difference. No serious adverse events were observed. Conclusions and Relevance: In this randomized clinical trial, the results demonstrated that neuromuscular exercises and pain neuroscience education were not superior to pain neuroscience education alone in participants with chronic pain after TKA. Approximately one-third of the participants, regardless of intervention, experienced clinically important improvements. Future studies should investigate which patient characteristics indicate a favorable response to exercises and/or pain neuroscience education. Trial Registration: ClinicalTrials.gov Identifier: NCT03886259.

Investigating the fluctuating nature of post-COVID pain symptoms in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP multicenter study.

Objective: This cohort study used Sankey plots and exponential bar plots for visualizing the fluctuating nature and trajectory of post-COVID pain in previously hospitalized COVID-19 survivors. Methods: A cohort of 1266 subjects hospitalised because of COVID-19 during the first wave of the pandemic were scheduled for a telephone interview at 8.4 (T1), 13.2 (T2), and 18.3 (T3) months in average after hospitalization for collecting data about post-COVID pain. Patients were asked for about pain symptomatology that was attributed to the infection. Hospitalization and clinical data were collected from medical records. Results: The prevalence of myalgia as COVID-19-associated symptom was 29.82% (n = 389) at hospitalization (T0). The prevalence of post-COVID pain was 41.07% (n = 520) at T1, 34.29% (n = 434) at T2, and 28.47% (n = 360) at T3. The recovery exponential curve revealed a decrease trend visualizing that post-COVID pain improved over the time span investigated. Pain in the lower extremity and widespread pain were the most prevalent locations. Female sex (OR 1.507, 95% CI 1.047-2.169), pre-existing pain symptoms (OR 1.724, 95% CI 1.237-2.403), headache as onset-symptom (OR 2.374, 95% CI 1.550-3.639), days at hospital (OR 1.012, 95% CI 1.000-1.025), and presence of post-COVID pain at T1 (OR 13.243, 95% CI 9.428-18.601) were associated with post-COVID pain at T2. Only the presence of post-COVID pain at T1 (OR 5.383, 95% CI 3.896-7.439) was associated with post-COVID pain at T3. Conclusion: Current results show a fluctuating evolution with a decreasing tendency of post-COVID pain during the first years after hospitalization. The development of post-COVID pain soon after SARS-CoV-2 infection predispose for long-lasting chronic pain.

Evaluating Sensitization-associated, Neuropathic-like Symptoms and Psychological Factors in Patients With Interstitial Lung Disease.

The aims of this study were to phenotype pain in patients with interstitial lung disease (ILD) by investigating the association between sensitization-associated symptoms with quality of life, anxiety/depression, pain catastrophizing, and kinesiophobia levels and identifying those risk factors explaining the variance of quality of life in individuals with ILD and pain. One hundred and thirty-two (38.6% women, mean age: 70, standard deviation: 10.5 years) patients with ILD completed clinical (age, sex, height, weight), psychological (Hospital Anxiety and Depression Scale [HADS] and the Pittsburgh Sleep Quality Index), and health-related quality of life (EQ-5D-5L) variables, as well as the Central Sensitization Inventory (CSI), the Self-Report Leeds Assessment of Neuropathic Symptoms (S-LANSS), Pain Catastrophizing Scale, and Tampa Scale for Kinesiophobia (TSK-11) questionnaires. The prevalence of sensitization-associated symptomatology (CSI), neuropathic-like features (S-LANSS), anxiety symptoms, depressive symptoms, or poor sleep was 20.5%, 23.5%, 23.6%, 22.9%, or 51.6%. Significant associations between CSI, S-LANSS, HADS-A, HADS-D, Pain Catastrophizing Scale, TSK-11, and EQ-5D-5L (.220 < r < .716) were found. The regression analysis revealed that CSI, TSK-11, and HADS-D explained 44.8% of the variance of EQ-5D-5L (r2 adjusted: .448). This study found the presence of sensitization-associated and neuropathic-like symptoms as well as other central nervous system-derived symptoms, such as anxiety, depression, poor sleep, pain catastrophizing, and kinesiophobia in 25% of ILD patients with pain. Sensitization-associated symptoms, depression, and kinesiophobia were associated with a worse quality of life. These findings would support that individuals with ILD can exhibit different pain phenotypes, including nociplastic-like pain phenotype based on self-reported measurements. PERSPECTIVE: Pain in patients with ILD can fulfill features of different phenotypes, including nociplastic pain, when sensory, emotional, and cognitive mechanisms are involved at the same time.

Lumbar intervertebral disc degeneration in low back pain.

Intervertebral disc degeneration is characterized by deterioration in structural support that is potentially followed by stimulated neuronal ingrowth, and dysfunction of cellular physiology in the disc. Discogenic low back pain originates from nociceptors within the intervertebral disc or the cartilage endplate. This narrative review examines the mechanisms of disc degeneration, the association between degeneration and pain, and the current diagnosis and treatment of discogenic low back pain. Mechanisms of disc degeneration include dysregulated homeostasis of the extracellular matrix of the disc, altered spine mechanics, DNA damage, oxidative stress, perturbed cell signaling pathways, and cellular senescence. Although disc degeneration is more common in individuals with low back pain than in asymptomatic ones, degeneration occurs in a large proportion of asymptomatic individuals. Therefore, degeneration itself is not sufficient to trigger low back pain. Imaging and discography are common diagnostic tools of discogenic low back pain but have limited validity to diagnose discogenic pain. Most of current treatments options are not specific to discogenic pain but are unspecific treatments of low back pain of any origin. There is an urgent need to clarify and distinguish the molecular mechanisms of discogenic pain from mechanisms of disc degeneration that are not involved in nociception. Future research should make use of current methods to study molecular mechanisms of human pain in comprehensively and quantitatively phenotyped patients with low back pain, with the objective to identify molecular triggers of discogenic pain and determine the relationship between molecular mechanisms, pain, and patient-relevant outcomes.

Sex moderates the association between quantitative sensory testing and acute and chronic pain after total knee/hip arthroplasty.

OBJECTIVES: Acute postsurgical pain (APSP) may persist over time and become chronic. Research on predictors for APSP and chronic postsurgical pain (CPSP) has produced inconsistent results. This observational study aimed to analyze psychological and psychophysical variables associated with APSP and CPSP after total knee or hip arthroplasty, and to explore the role of sex. METHODS: Assessments were conducted before surgery, 48 h, and 3 months postsurgery, including questionnaires (sociodemographic, pain related, and psychological) and quantitative sensory testing (QST). Hierarchical linear regression models analyzed potential predictors of APSP and CPSP, and moderation analyses evaluated the role of sex. RESULTS: The study included 63 participants undergoing total knee (34, 54%) or hip (29, 46%) arthroplasty. Thirty-one (49.2%) were female and 32 (50.8%) were male. APSP (48 h) was associated with impaired conditioned pain modulation (CPM) (ß = 0.301, p = 0.019). CPSP (3 months) was associated with being female (ß = 0.282, p = 0.029), longer presurgical pain duration (ß = 0.353, p = 0.006), knee arthroplasty (ß = -0.312, p = 0.015), higher APSP intensity (ß = 373, p = 0.004), and impaired CPM (ß = 0.126, p = 0.004). In multivariate analysis, these clinical variables were significant predictors of CPSP, unlike sex, and CPM (adj. R 2 = 0.349). Moderation analyses showed that wind-up ratio (WUR) was a significant predictor of APSP in men (WUR × sex: b = -1.373, p = 0.046) and CPM was a significant predictor of CPSP in women (CPM × sex: b = 1.625, p = 0.016). CONCLUSIONS: Specific QST parameters could identify patients at risk for high-intensity APSP and CPSP, with sex as a moderator. This has important clinical implications for patient care, paving the way for developing tailored preventive pain management strategies.

Pain catastrophizing in the elderly: An experimental pain study.

OBJECTIVES: Pain catastrophizing in the aging population has not been studied in great detail. Existing investigations have reported conflicting results on the effects of age on pain catastrophizing in relation to pain responses. This study investigated the relationship between pain catastrophizing, and its individual components (rumination, magnification, and helplessness), and the responses to standardized experimental pain stimuli in old and young, healthy adults. METHODS: Sixty-six volunteers (32 old: 65-87, 18 females; 34 young: 20-35, 17 females) participated in the study. Pain catastrophizing including the components of rumination, magnification, and helplessness was assessed with the pain catastrophizing scale (PCS). Experimental pain was induced by applying predefined pressure stimulations to the trapezius muscle. Pain intensity and unpleasantness were assessed using numerical rating scales. Pain catastrophizing levels and pain responses were statistically compared between the two age groups. RESULTS: Elderly individuals reported significantly (p = 0.028) lower scores of pain catastrophizing (Med = 5; interquartile range [IQR] = 14) than younger individuals; this difference was driven by the significantly lower components of rumination (Med = 2; IQR = 4; p = 0.017) and helplessness (Med = 2; IQR = 7; p = 0.049). A larger proportion of young (57.8%) rated pain catastrophizing at high levels, with scores above the 75th percentile (Med = 20). Additionally, elderly reported the lowest pain intensity (Med = 5; p = 0.034) and pain unpleasantness (Med = 4.5; p = 0.011) responses to the experimental pressure stimuli. In the elderly group, pain unpleasantness was positively and significantly associated with pain catastrophizing (r s = 0.416, p = 0.021), rumination (r s = 0.42, p = 0.019), and helplessness (r s = 0.434, p = 0.015), respectively. No associations were found in the young group. CONCLUSIONS: Elderly reported lower PCSs than young adults. Rumination and helplessness were reduced in the elderly group. The elderly population showed positive correlations between catastrophizing levels and pain unpleasantness to standardized pressure pain stimuli. Results supported the view that elderly possess resilience over specific domains of pain catastrophizing that could counteract pain perception due to physiological decline.

World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: V. Physical examination standards in endometriosis research.

OBJECTIVE: The World Endometriosis Research Foundation established the Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) to create standardized documentation tools (with common data elements) to facilitate the comparison and combination of data across different research sites and studies. In 2014, 4 data research standards were published: clinician-reported surgical data, patient-reported clinical data, and fluid and tissue biospecimen collection. Our current objective is to create an EPHect standard for the clinician-reported physical examination (EPHect-PE) for research studies. DESIGN: An international consortium involving 26 clinical and academic experts and patient partners from 11 countries representing 25 institutions and organizations. Two virtual workshops, followed by the development of the physical examination standards underwent multiple rounds of iterations and revisions. SUBJECTS: N/A MAIN OUTCOME MEASURE(S): N/A RESULT(S): The EPHect-PE tool provides standardized assessment of physical examination characteristics and pain phenotyping. Data elements involve examination of back and pelvic girdle; abdomen including allodynia and trigger points; vulva including provoked vestibulodynia; pelvic floor muscle tone and tenderness; tenderness on unidigital pelvic examination; presence of pelvic nodularity; uterine size and mobility; presence of adnexal masses; presence of incisional masses; speculum examination; tenderness and allodynia at an extra-pelvic site (e.g., forearm); and recording of anthropometrics. CONCLUSION(S): The EPHect-PE standards will facilitate the standardized documentation of the physical examination, including the assessment and documentation of examination phenotyping of endometriosis-associated pelvic pain.

Intra-articular injection of gold micro-particles with hyaluronic acid for painful knee osteoarthritis.

BACKGROUND: Recently, in an open pilot study, we found up to two years, a potential pain-relieving effect of intra-articular gold micro-particles using the patient's synovial fluid for patients with knee osteoarthritis (KOA). During the study the excluded group of patients, due to multisite pain, co-morbidities, and other exclusion criteria., received intra-articular gold micro-particles using hyaluronic acid,. We aimed to identify if pre-treatment characteristics influence the global outcome two years after intra-articular treatment for painful KOA with gold microparticles using hyaluronic acid. METHODS: Using hyaluronic acid as the carrier, 136 patients with KOA received intraarticular injections with 20 mg gold microparticles (72.000 particles, 20-40 µm in diameter). In the analysis, we included the Global Rating of Change Scale, Pain Detect Questionnaire (PDQ), Body Mass Index (BMI), and Kellgren & Lawrence score at the inclusion, Western Ontario, and McMaster Universities Osteoarthritis Index (WOMAC) sub-scores for pain, stiffness, and function at inclusion and two years. RESULTS: On the Global Rating Change Scale, 69.1% of patients reported a positive effect, 28.7% no effect, and 2.2% worse. PDQ and the three WOMAC subscores all improved at two years of follow-up. PDQ ≥ 13 (P = 0.028), BMI (P = 0.022) and Kellgren & Lawrence grade 4 (P = 0.028) at inclusion reduced the effect with a minor odds ratio compared to the baseline effect of treatment (P = 0.025). WOMAC subscores at inclusion did not influence the outcome (P > 0.5). CONCLUSIONS: Severe osteoarthritis, obesity, and neuropathic pain, reduced the effect of intra-articular gold microparticles for knee OA. TRIAL REGISTRATION: The study followed the principles of the Declaration of Helsinki and was approved by the local ethics committee of the North Denmark Region by 27/07/2016 (N-20,160,045). The regional data protection agency approved the project by 06/07/2016 (2008-58-0028, ID 2016 - 116) and registered in ClinicalTrial.Gov by 04/01/2018 (NCT03389906).

Quantitative sensory testing, psychological factors, and quality of life as predictors of current and future pain in patients with knee osteoarthritis.

ABSTRACT: Substantial interindividual variability characterizes osteoarthritis (OA) pain. Previous findings identify quantitative sensory testing (QST), psychological factors, and health-related quality of life as contributors to OA pain and predictors of treatment outcomes. This exploratory study aimed to explain baseline OA pain intensity and predict OA pain after administration of a nonsteroidal anti-inflammatory drug in combination with paracetamol for 3 weeks. The Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score was used to estimate OA pain presentation. One hundred one patients were assessed at baseline and follow-up using QST (pressure pain thresholds and temporal summation of pain [TSP]), symptoms of depression and anxiety, pain catastrophizing scales (PCSs), and health-related quality of life. Linear regression with backward selection identified that PCS significantly explained 34.2% of the variability in baseline KOOS pain, with nonsignificant contributions from TSP. Pain catastrophizing score and TSP predicted 29.3% of follow-up KOOS pain, with nonsignificant contributions from symptoms of anxiety. When assessed separately, PCS was the strongest predictor (32.2% of baseline and 24.1% of follow-up pain), but QST, symptoms of anxiety and depression, PCS, and quality of life also explained some variability in baseline and follow-up knee OA pain. Further analyses revealed that only TSP and PCS were not mediated by any other included variables, highlighting their role as unique contributors to OA pain presentation. This study emphasizes the importance of embracing a multimodal approach to OA pain and highlights PCS and TSP as major contributors to the baseline OA pain experience and the OA pain experience after OA treatment.

A potential link between inflammatory profiles, clinical pain, pain catastrophizing and long-term outcomes after total knee arthroplasty surgery.

BACKGROUND: Chronic postoperative pain after total knee replacement (TKR) is a major clinical problem. It is still unclear if specific inflammatory mediators are associated with long-term postoperative pain complications. The current exploratory study aimed to (1) evaluate a multiplex of inflammatory mediators 5 years after TKR surgery in patients with different degrees of postoperative pain intensities and (2) study any association of the markers with clinical pain intensity, cognitive and functional outcomes. METHODS: Plasma samples were collected 5 years after TKR surgery from 76 knee patients (43 females; 33 males) and analysed for 44 inflammatory markers. Pain (using visual analogue scale, VAS), the pain catastrophizing scale (PCS) and the Oxford knee score (OKS) were evaluated. Patients were categorized as high or low groups based on VAS, PCS and OKS scores. Associations between inflammatory markers, VAS, PCS and OKS were analysed and the marker expressions were compared between groups. RESULTS: Pearson's correlations found 12 biomarkers associated with VAS (p < 0.05), 4 biomarkers with PCS and 3 biomarkers with OKS (p < 0.05). Four markers were altered in patients suffering from high compared to low chronic postoperative pain, three markers were altered in high compared to low catastrophizers and three markers were altered in patients with poor functional scores (p < 0.05). CONCLUSIONS: The present exploratory study suggests that low-grade inflammation might be present in a subset of patients with high pain, high catastrophizing and low function 5 years after TKR. These exploratory results provide insights into some of the long-term postoperative complications after TKR surgery. SIGNIFICANCE STATEMENT: This exploratory study evaluated a subset of inflammatory markers and the association to clinical pain intensity, knee function and pain catastrophizing in patients 5 years after total knee replacement surgery. Our results provide insights into the understanding of the underlying mechanisms that may drive the long experience of pain after TKR surgery.

Inflammatory Polymorphisms (IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252) Are Not Associated with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors.

The aim of this study was to identify the association between four selected inflammatory polymorphisms with the development of long-term post-COVID symptoms in subjects who had been hospitalized due to SARS-CoV-2 infection during the first wave of the pandemic. These polymorphisms were selected as they are associated with severe COVID-19 disease and cytokine storm, so they could be important to prognoses post-COVID. A total of 408 (48.5% female, age: 58.5 ± 14.0 years) previously hospitalized COVID-19 survivors participated. The three potential genotypes of the following four single-nucleotide polymorphisms, IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252, were obtained from non-stimulated saliva samples of the participants. The participants were asked to self-report the presence of any post-COVID symptoms (defined as symptoms that had started no later than one month after SARS-CoV-2 acute infection) and whether the symptoms persisted at the time of the study. At the time of the study (mean: 15.6, SD: 5.6 months after discharge), 89.4% of patients reported at least one post-COVID symptom (mean number of symptoms: 3.0; SD: 1.7). Fatigue (69.3%), pain (40.9%), and memory loss (27.2%) were the most prevalent post-COVID symptoms in the total sample. Overall, no differences in the post-COVID symptoms depending on the IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252 genotypes were seen. The four SNPs assessed, albeit having been previously associated with inflammation and COVID-19 severity, did not cause a predisposition to the development of post-COVID symptoms in the previously hospitalized COVID-19 survivors.