Tag: pain

Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series

Abstract:

Introduction: Neurological sequelae following SARS-CoV-2 infection still represent a serious concern both for neurologists and neuroscientists. In our paper, we investigated pain, myalgia, and fatigue as symptoms in long-COVID patients with an electrophysiological approach, comprising the evaluation of sympathetic skin responses (SSRs) and quantitative electromyography (qEMG).

Materials and methods: Twelve patients were enrolled (mean age, 47.7 ± 11.6 years), referred to our attention because of myalgia, pain, or muscle cramps, which persisted about 6 months after the diagnosis of SARS-CoV-2 infection. They underwent conventional electroneurography (ENG), needle electromyography (EMG), and SSRs; moreover, qEMG was performed by sampling at least 20 motor unit potentials (20-30 MUPs) during weak voluntary contraction in deltoid and tibialis anterior muscles. The mean duration, amplitude, and percentage of polyphasic potentials were assessed and compared with healthy and age-matched volunteers.

Results: ENG did not disclose significant changes compared to healthy subjects; needle EMG did not reveal denervation activity. In addition, qEMG showed MUPs similar to those recorded in healthy volunteers in terms of polyphasia (deltoid: p = 0.24; TA: p = 0.35), MUP area (deltoid: p = 0.45; TA: p = 0.44), mean duration (deltoid: p = 0.06; TA: p = 0.45), and amplitude (deltoid: p = 0.27; TA: p = 0.63). SSRs were not recordable from lower limbs in seven patients (58%) and from the upper ones in three of them (25%).

Conclusion: Our data suggest an involvement of the autonomic system, with a focus on cholinergic efferent sympathetic activity, without any evidence of myopathic changes.

Source: Bocci T, Bertini A, Campiglio L, Botta S, Libelli G, Guidetti M, Priori A. Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series. Neurol Sci. 2023 Apr;44(4):1147-1153. doi: 10.1007/s10072-023-06637-8. Epub 2023 Feb 3. PMID: 36735149; PMCID: PMC9896447. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9896447/ (Full study)

Is Central Sensitisation the Missing Link of Persisting Symptoms after COVID-19 Infection?

Abstract:

Patients recovered from a COVID-19 infection often report vague symptoms of fatigue or dyspnoea, comparable to the manifestations in patients with central sensitisation. The hypothesis was that central sensitisation could be the underlying common aetiology in both patient populations. This study explored the presence of symptoms of central sensitisation, and the association with functional status and health-related quality of life, in patients post COVID-19 infection.

Patients who were previously infected with COVID-19 filled out the Central Sensitisation Inventory (CSI), the Post-COVID-19 Functional Status (PCFS) Scale and the EuroQol with five dimensions, through an online survey. Eventually, 567 persons completed the survey. In total, 29.73% of the persons had a score of <40/100 on the CSI and 70.26% had a score of ≥40/100. Regarding functional status, 7.34% had no functional limitations, 9.13% had negligible functional limitations, 37.30% reported slight functional limitations, 42.86% indicated moderate functional limitations and 3.37% reported severe functional limitations.

Based on a one-way ANOVA test, there was a significant effect of PCFS Scale group level on the total CSI score (F(4,486) = 46.17, p < 0.001). This survey indicated the presence of symptoms of central sensitisation in more than 70% of patients post COVID-19 infection, suggesting towards the need for patient education and multimodal rehabilitation, to target nociplastic pain.

Source: Goudman L, De Smedt A, Noppen M, Moens M. Is Central Sensitisation the Missing Link of Persisting Symptoms after COVID-19 Infection? J Clin Med. 2021 Nov 28;10(23):5594. doi: 10.3390/jcm10235594. PMID: 34884296; PMCID: PMC8658135. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658135/ (Full text)

Could the fibromyalgia syndrome be triggered or enhanced by COVID-19?

Abstract:

Fibromyalgia (FM) is a complex disease with an uncertain aetiology and intricate pathophysiology. Although its genesis is not fully explained, potential environmental factors, such as viral infections might trigger FM or worsen patients’ clinical outcomes.

The SARS-CoV-2 virus may affect central and peripheral nervous systems, leading to musculoskeletal, neurological, and psychological disturbances. These symptoms might persist at least 12 months beyond the recovery, often referred to as post-COVID syndrome, which resembles FM syndrome. In this sense, we argued the potential consequences of COVID-19 exclusively on FM syndrome.

First, we have described post-COVID syndrome and its painful symptoms. Afterwards, we argued whether FM syndrome could be triggered or enhanced by COVID-19 infection or by numerous and persistent stressors imposed daily by the pandemic setting (isolation, uncertainty, depression, mental stress, generalized anxiety, and fear of the virus). In addition, we have demonstrated similarities between pathophysiological mechanisms and cardinal symptoms of FM and COVID-19, speculating that SARS-CoV-2 might represent a critical mediator of FM or an exacerbator of its symptoms once both syndromes share similar mechanisms and complaints.

Therefore, pharmacologic and non-pharmacological approaches commonly used to treat FM could serve as strategic therapies to attenuate painful and neurological manifestations of post-COVID syndrome. Although it is still theoretical, clinicians and researchers should be alert of patients who develop symptoms similar to FM or those who had their FM symptoms increased post-COVID to manage them better.

Source: Fialho MFP, Brum ES, Oliveira SM. Could the fibromyalgia syndrome be triggered or enhanced by COVID-19? Inflammopharmacology. 2023 Feb 27:1–19. doi: 10.1007/s10787-023-01160-w. Epub ahead of print. PMID: 36849853; PMCID: PMC9970139. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9970139/ (Full text)

Pain and Clinical Presentation: A Cross-Sectional Study of Patients with New-Onset Chronic Pain in Long-COVID-19 Syndrome

Abstract:

The aim of this study was to evaluate the characteristics of pain (i.e., pain intensity, pain interference, clinical presentation) in Long-COVID-19 patients and compare the location of pain between successfully recovered COVID-19 patients and healthy matched controls.
A cross-sectional case-control study was carried out. Long-COVID-19 patients, age- and sex-matched patients with a history of COVID-19 who had successfully recovered, and healthy controls were included. Outcomes included were pain characteristics (Brief Pain Inventory and Short-Form McGill Pain Questionnaire) and clinical presentation (Widespread Pain Index and Euroqol-5 Dimensions 5 Levels Visual Analogue Scale). Sixty-nine patients with Long-COVID-19 syndrome, sixty-six successfully recovered COVID-19 patients, and sixty-seven healthy controls were evaluated.
Patients with Long-COVID-19 syndrome showed greater pain intensity and interference. In addition, they showed worse quality of life and greater widespread pain, with the most frequent locations of pain being the neck, legs, and head.
In conclusion, patients with Long-COVID-19 syndrome show a high prevalence of pain, characterized by widespread pain of moderate intensity and interference, with the most frequent locations being the neck, legs, and head, significantly affecting the quality of life of these patients.
Source: Calvache-Mateo A, López-López L, Martín-Núñez J, Heredia-Ciuró A, Granados-Santiago M, Ortiz-Rubio A, Valenza MC. Pain and Clinical Presentation: A Cross-Sectional Study of Patients with New-Onset Chronic Pain in Long-COVID-19 Syndrome. International Journal of Environmental Research and Public Health. 2023; 20(5):4049. https://doi.org/10.3390/ijerph20054049 https://www.mdpi.com/1660-4601/20/5/4049 (Full text)

Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review

Abstract:

The ongoing pandemic of COVID-19 has caused more than 6.7 million tragic deaths, plus, a large percentage of people who survived it present a myriad of chronic symptoms that last for at least 6 months; this has been named as long COVID. Some of the most prevalent are painful symptoms like headache, joint pain, migraine, neuropathic-like pain, fatigue and myalgia. MicroRNAs are small non-coding RNAs that regulate genes, and their involvement in several pathologies has been extensively shown. A deregulation of miRNAs has been observed in patients with COVID-19.
The objective of the present systematic review was to show the prevalence of chronic pain-like symptoms of patients with long COVID and based on the expression of miRNAs in patients with COVID-19, and to present a proposal on how they may be involved in the pathogenic mechanisms of chronic pain-like symptoms.
A systematic review was carried out in online databases for original articles published between March 2020 to April 2022; the systematic review followed the PRISMA guidelines, and it was registered in PROSPERO with registration number CRD42022318992. A total of 22 articles were included for the evaluation of miRNAs and 20 regarding long COVID; the overall prevalence of pain-like symptoms was around 10 to 87%, plus, the miRNAs that were commonly up and downregulated were miR-21-5p, miR-29a,b,c-3p miR-92a,b-3p, miR-92b-5p, miR-126-3p, miR-150-5p, miR-155-5p, miR-200a, c-3p, miR-320a,b,c,d,e-3p, and miR-451a.
The molecular pathways that we hypothesized to be modulated by these miRNAs are the IL-6/STAT3 proinflammatory axis and the compromise of the blood–nerve barrier; these two mechanisms could be associated with the prevalence of fatigue and chronic pain in the long COVID population, plus they could be novel pharmacological targets in order to reduce and prevent these symptoms.
Source: Reyes-Long S, Cortés-Altamirano JL, Bandala C, Avendaño-Ortiz K, Bonilla-Jaime H, Bueno-Nava A, Ávila-Luna A, Sánchez-Aparicio P, Clavijo-Cornejo D, Dotor-LLerena AL, Cabrera-Ruiz E, Alfaro-Rodríguez A. Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review. International Journal of Molecular Sciences. 2023; 24(4):3574. https://doi.org/10.3390/ijms24043574 https://www.mdpi.com/1422-0067/24/4/3574 (Full text)

Characteristics associated with physical functioning and fatigue in patients with chronic fatigue syndrome (CFS): secondary analyses of a randomized controlled trial

Abstract

Objective: This study aimed to explore associations at the group level between patient characteristics at baseline and the outcomes of physical functioning and fatigue in patients with chronic fatigue syndrome (CFS) participating in a randomized controlled trial on cognitive behavioural therapy (CBT).

Methods/design: Consecutively, 236 adult participants fulfilling the Centres for Disease Control and Prevention (CDC) 1994 criteria for CFS were randomly allocated to either 16 weeks of standard CBT, 8 weeks of Interpersonal CBT or a treatment as usual control group. In secondary analyses we investigated how gender, age, pain, anxiety, depression, memory and VO2max at baseline were associated with physical function and fatigue before and after treatment, controlling for the CBT-interventions and the baseline levels of the outcome measures.

For the two groups receiving CBT, a 1-year follow-up analysis was also done. Bivariate and multivariable linear regression was used to explore the targeted associations.

Results: At baseline, less pain (p < .001) and higher VO2max (p = 0.014) were associated with better physical function, while better memory (p = 0.001) and fewer depressive symptoms (p = 0.017) were associated with less fatigue. Better memory and physical function at baseline (p = 0.015 and p < .001, respectively) and male gender (p = 0.003) were associated with higher physical function post-intervention.

Male gender (p = 0.010) was associated with higher physical function at 1-year follow-up. Fatigue severity at baseline was the only variable associated with follow up scores for fatigue (p < .001).

Conclusion: Our findings show that fatigue and physical function were associated with different types of characteristics at baseline, indicating a heterogeneity among CFS patients.

Source: Merethe Eide Gotaas, Tormod Landmark, Anne S. Helvik & Egil A. Fors (2023) Characteristics associated with physical functioning and fatigue in patients with chronic fatigue syndrome (CFS): secondary analyses of a randomized controlled trial, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2023.2175521 https://www.tandfonline.com/doi/full/10.1080/21641846.2023.2175521 (Full text)

Muscle sodium content in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Muscle fatigue and pain are key symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Although the pathophysiology is not yet fully understood, there is ample evidence for hypoperfusion which may result in electrolyte imbalance and sodium overload in muscles. Therefore, the aim of this study was to assess levels of sodium content in muscles of patients with ME/CFS and to compare these to healthy controls.

Methods: Six female patients with ME/CFS and six age, BMI and sex matched controls underwent 23Na-MRI of the left lower leg using a clinical 3T MR scanner before and after 3 min of plantar flexion exercise. Sodium reference phantoms with solutions of 10, 20, 30 and 40 mmol/L NaCl were used for quantification. Muscle sodium content over 40 min was measured using a dedicated plugin in the open-source DICOM viewer Horos. Handgrip strength was measured and correlated with sodium content.

Results: Baseline tissue sodium content was higher in all 5 lower leg muscle compartments in ME/CFS compared to controls. Within the anterior extensor muscle compartment, the highest difference in baseline muscle sodium content between ME/CFS and controls was found (mean ± SD; 12.20 ± 1.66 mM in ME/CFS versus 9.38 ± 0.71 mM in controls, p = 0.0034). Directly after exercise, tissue sodium content increased in gastrocnemius and triceps surae muscles with + 30% in ME/CFS (p = 0.0005) and + 24% in controls (p = 0.0007) in the medial gastrocnemius muscle but not in the extensor muscles which were not exercised. Compared to baseline, the increase of sodium content in medial gastrocnemius muscle was stronger in ME/CFS than in controls with + 30% versus + 17% to baseline at 12 min (p = 0.0326) and + 29% versus + 16% to baseline at 15 min (p = 0.0265). Patients had reduced average handgrip strength which was associated with increased average muscle tissue sodium content (p = 0.0319, R2 = 0.3832).

Conclusion: Muscle sodium content before and after exercise was higher in ME/CFS than in healthy controls. Furthermore, our findings indicate an inverse correlation between muscle sodium content and handgrip strength. These findings provide evidence that sodium overload may play a role in the pathophysiology of ME/CFS and may allow for potential therapeutic targeting.

Source: Petter E, Scheibenbogen C, Linz P, Stehning C, Wirth K, Kuehne T, Kelm M. Muscle sodium content in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. J Transl Med. 2022 Dec 9;20(1):580. doi: 10.1186/s12967-022-03616-z. PMID: 36494667. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03616-z (Full text)

Serological biomarkers of COVID-19 severity at hospital admission are not related to long-term post-COVID pain symptoms in hospitalized COVID-19 survivors

Abstract:

This study investigated the association between serological biomarkers at hospital admission with the development of long-term post-COVID pain symptoms in previously hospitalized coronavirus disease, 2019 (COVID-19) survivors. A cohort study including patients hospitalised because of COVID-19 in 1 urban hospital of Madrid (Spain) during the first wave of the outbreak was conducted. Hospitalisation data, clinical data, and 11 serological biomarkers were collected at hospital admission. Participants were scheduled for an individual telephone interview after hospital discharge for collecting data about post-COVID pain symptoms.

A total of 412 patients (mean age: 62, SD: 15 years; 46.1% women) were assessed twice, at a mean of 6.8 and 13.2 months after discharge. The prevalence of post-COVID pain symptoms was 42.7% (n = 176) and 36.2% (n = 149) at 6.8 and 13.2 months after hospital discharge. Patients reporting post-COVID pain exhibited a greater number of COVID-19-associated symptoms at hospital admission, more medical comorbidities, higher lymphocyte count, and lower glucose and creatine kinase levels (all, P < 0.01) than those not reporting post-COVID pain. The multivariate analysis revealed that lower creatine kinase and glucose levels were significantly associated, but just explaining 6.9% of the variance of experiencing post-COVID pain.

In conclusion, the association between serological biomarkers associated with COVID-19 severity at hospital admission and the development of post-COVID pain is small. Other factors, eg, higher number of COVID-19 onset symptoms (higher symptom load) could be more relevant for the development of post-COVID pain. Because inflammatory biomarkers were not directly analyzed, they may have stronger predictive strengths for the development of post-COVID pain symptoms.

Source: Fernández-de-Las-Peñas C, Ryan-Murua P, de-la-Llave-Rincón AI, Gómez-Mayordomo V, Arendt-Nielsen L, Torres-Macho J. Serological biomarkers of COVID-19 severity at hospital admission are not related to long-term post-COVID pain symptoms in hospitalized COVID-19 survivors. Pain. 2022 Nov 1;163(11):2112-2117. doi: 10.1097/j.pain.0000000000002608. Epub 2022 Feb 3. PMID: 35121694; PMCID: PMC9560903.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9560903/ (Full text)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-COVID Syndrome: A Common Neuroimmune Ground?

Abstract:

A Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown aetiology under growing interest now in view of the increasingly recognized post-COVID syndrome as a new entity with similar clinical presentation.

We performed the first cross-sectional study of ME/CFS in community population in Russia and then described and compared some clinical and pathophysiological characteristics of ME/CFS and post-COVID syndrome as neuroimmune disorders.

Of the cohort of 76 individuals who suggested themselves suffering from ME/CFS 56 subsequently were confirmed as having CFS/ME according to ≥1 of the 4 most commonly used case definition.

Of the cohort of 14 individuals with post-COVID-19 syndrome 14 met diagnostic criteria for ME/CFS. The prevalence of clinically expressed and subclinical anxiety and depression in ME / CFS and post-COVID ME/CFS did not differ significantly from that in healthy individuals.

Severity of anxiety / depressive symptoms did not correlate with the severity of fatigue neigther in ME / CFS nor in post-COVID ME/CFS, but the positive correlation was found between the severity of fatigue and 20 other symptoms of ME / CFS related to the domains of “post-exertional exhaustion”, “immune dysfunction”, “sleep disturbances”, “dysfunction of the autonomic nervous system”, “neurological sensory / motor disorders” and “pain syndromes”.

Immunological abnormalities were identified in 12/12 patients with ME / CFS according to the results of laboratory testing.

The prevalence of postural orthostatic tachycardia assessed by the active standing test was 37.5% in ME / CFS and 75.0% in post-COVID ME/CFS (the latter was higher than in healthy controls, p = 0.02).  There was a more pronounced increase in heart rate starting from the 6th minute of the test in post-COVID ME/CFS compared with the control group.

Assessment of the functional characteristics of microcirculation by laser doppler flowmetry revealed obvious and very similar changes in ME/CFS and post-COVID ME/CFS compared to the healthy controls.  The identified pattern corresponded to the hyperemic form of microcirculation disorders, usually observed in acute inflammatory processes or in deficiency of systemic vasoconstriction influences.

Source: Ryabkova, V.A.; Gavrilova, N.Y.; Fedotkina, T.V.; Churilov, L.P.; Shoenfeld, Y. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-COVID Syndrome: A Common Neuroimmune Ground?. Preprints 2022, 2022090289 (doi: 10.20944/preprints202209.0289.v1) https://www.preprints.org/manuscript/202209.0289/v1 (Full study available as PDF file)

The Significance of Pain Drawing as a Screening Tool for Cervicogenic Headache and Associated Symptoms in Chronic Fatigue

Abstract:

Purpose: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with a broad spectrum of symptoms, including headache. A simple, yet powerful tool – the pain drawing identifies essential aspects such as pain distribution. The aim with this study was to 1) evaluate the significance of pain drawing as a screening tool for cervicogenic headache using a predefined C2 pain pattern, 2) assess whether there was an association between dizziness/imbalance and a C2 pain pattern, and 3) compare subgroups according to the pain drawing with respect to pain characteristics and quality of life.

Patients and methods: Pain drawings and clinical data from 275 patients investigated for ME/CFS were stratified into: 1) cervicogenic headache as determined by a C2 pain pattern, 2) headache with no C2 pain pattern, and 3) no headache. For inference logistic regression presented with odds ratios (OR) and 95% confidence intervals (95% CI) and Kruskal-Wallis test were applied.

Results: One hundred sixteen participants (42%) were stratified to the group for which the pain drawing corresponded to the C2 pain pattern, thus indicating putative cervicogenic origin of the headache. Dizziness/imbalance was strongly associated with a C2 pain pattern; OR 6.50 ([95% CI 2.42-17.40] p ˂ 0.00), whereas this association was non-significant for patients with headache and no C2 pain pattern. Those demonstrating a C2 pain pattern reported significantly higher pain intensity (p = 0.00) and greater pain extent (p = 0.00) than the other groups, and lower health-related quality of life (p = 0.00) than the group with no headache.

Conclusion: For patients with chronic fatigue who present with a C2 pain pattern (interpreted as cervicogenic headache) the pain drawing seems applicable as a screening tool for signs associated with neuropathic and more severe pain, dizziness and reduced quality of life as detection of these symptoms is essential for targeted treatment.

Source: Bernhoff G, Huhmar HM, Rasmussen-Barr E, Bunketorp Käll L. The Significance of Pain Drawing as a Screening Tool for Cervicogenic Headache and Associated Symptoms in Chronic Fatigue. J Pain Res. 2022 Aug 27;15:2547-2556. doi: 10.2147/JPR.S369470. PMID: 36061488; PMCID: PMC9432569. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9432569/ (Full text)