Tag: pain

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)

Experiences of pain in paediatric chronic fatigue syndrome/myalgic encephalomyelitis: a single-centre qualitative study

Abstract:

Background: Moderate to severe pain affects up to two-thirds of children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and is associated with worse fatigue and physical functioning. This research aims to gain a greater insight into pain experienced by these children.

Methods: Thematic analysis of qualitative data from semistructured interviews with 13 children with CFS/ME (mean age=15.3 years, 67% female) was completed.

Results: Thematic analysis enabled construction of three themes: children’s wide-ranging experiences of pain, negative impact of pain and lack of effective treatment for pain and nine subthemes. The first theme demonstrated highly varied pain experiences, ranging from ‘like [being]… on fire’, like ‘being stabbed’ to ‘like…lead’. Children experienced pain in multiple sites and with wide-ranging frequency and severity. The second theme highlighted the profound negative impact of pain on multiple aspects of children’s lives. Physical activity was severely impaired; some children ‘couldn’t leave bed’ or ‘couldn’t…brush [their] own hair’. Abdominal pain meant some would ‘go…days without eating’. Pain substantially impacted on mental health, leaving children feeling ‘agitated’, experiencing ‘really bad panic attacks’ or making them ‘[want to] breakdown’. Children felt they ‘can’t do the things that everyone else can do’, had ‘missed out’ and are ‘behind everyone’. Some avoided socialising as they ‘don’t want to stop everyone else’. The final theme demonstrates the absence of adequate treatment for pain, with participants reporting ‘nothing has ever really got rid of it’ and only ‘slightly [takes] the edge off’ and other experiencing side effects.

Conclusions: Pain in paediatric CFS/ME is highly variable, common and often results in severe physical limitation and poor mental health. Effective treatments for pain represent an unmet need.

Source: Serafimova T, Ascough C, Parslow RM, Crawley E. Experiences of pain in paediatric chronic fatigue syndrome/myalgic encephalomyelitis: a single-centre qualitative study. BMJ Paediatr Open. 2022 Feb;6(1):e001201. doi: 10.1136/bmjpo-2021-001201. Epub 2022 Feb 15. PMID: 36053633. https://bmjpaedsopen.bmj.com/content/6/1/e001201 (Full text)

Musculoskeletal symptoms in patients with Long COVID: A cross-sectional study on Iranian patients

Abstract:

Background and objectives: Latest studies have revealed that an increasing number of Corona Virus Disease of 2019 (COVID-19) patients may continue to feel symptoms after the acute phase. This study aimed to evaluate the prevalence of musculoskeletal symptoms after the acute phase of COVID-19 and its associated factors.

Methods: We designed a cross-sectional study from January 2021 to April 2021. An online questionnaire was designed and sent to patients who had recovered from COVID-19. The questionnaire contained questions on participants’ demographic characteristics, COVID-19 course at its acute phase, and musculoskeletal symptoms after recovering from COVID-19. Musculoskeletal symptoms associations with patients’ characteristic and COVID-19 course was evaluated.

Result: 239 patients, including 72 (30.1%) males and 167 (69.9%) females with a mean age of 37.96 years (SD=11.19), were included in the study. 98.74% of our patients had experienced at least one musculoskeletal symptom after recovering from COVID-19, and the most common symptom was fatigue, as 91.2% of participants experienced this symptom, followed by myalgia, headache, and low back pain. High BMI, hospitalization, and ICU admission were associated with a higher risk of musculoskeletal symptoms.

Conclusion: This study indicated a high prevalence of persistent musculoskeletal symptoms among patients who recovered from COVID-19. Modifiable factors, such as BMI, can be targeted to reduce the prevalence of musculoskeletal symptoms in COVID-19 survivors and reduce its burden.

Source: Azadvari M, Haghparast A, Nakhostin-Ansari A, Emami Razavi SZ, Hosseini M. Musculoskeletal symptoms in patients with Long COVID: A cross-sectional study on Iranian patients. Heliyon. 2022 Aug 11:e10148. doi: 10.1016/j.heliyon.2022.e10148. Epub ahead of print. PMID: 35971463; PMCID: PMC9367176. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367176/ (Full text)

Autoimmune Autonomic Dysfunction Syndromes: Potential Involvement and Pathophysiology Related to Complex Regional Pain Syndrome, Fibromyalgia, Chronic Fatigue Syndrome, Silicone Breast Implant-Related Symptoms and Post-COVID Syndrome

Abstract:

The pathophysiological mechanisms involved in chronic disorders such as complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant-related symptoms, and post-COVID syndrome have not been clearly defined. The course of the pain in some of the syndromes, the absence of evident tissue damage, and the predominance of alterations in the autonomic nervous system are shared similarities between them.

The production of autoantibodies following a trigger in the syndromes was previously described, for instance, trauma in complex regional pain syndrome, infectious agents in fibromyalgia, chronic fatigue syndrome, and post-COVID syndrome, and the immune stimulation by silicone in women with breast implants. In fact, the autoantibodies produced were shown to be directed against the autonomic nervous system receptors, leading to the amplification of the perception of pain alongside various clinical symptoms seen during the clinical course of the syndromes. Therefore, we viewed autoantibodies targeting the autonomic nervous system resulting in autonomic dysfunction as likely the most comprehensive explanation of the pathophysiology of the disorders mentioned.

Based on this, we aimed to introduce a new concept uniting complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant-related symptoms, and post-COVID syndrome, namely “autoimmune autonomic dysfunction syndromes”. Due to its etiological, pathophysiological, and clinical implications, the suggested term would be more precise in classifying the syndromes under one title. The new title would doubtlessly facilitate both laboratory and clinical studies aimed to improve diagnosis and make treatment options more directed and precise.

Source: Mahroum N, Shoenfeld Y. Autoimmune Autonomic Dysfunction Syndromes: Potential Involvement and Pathophysiology Related to Complex Regional Pain Syndrome, Fibromyalgia, Chronic Fatigue Syndrome, Silicone Breast Implant-Related Symptoms and Post-COVID Syndrome. Pathophysiology. 2022 Jul 28;29(3):414-425. doi: 10.3390/pathophysiology29030033. PMID: 35997389. https://www.mdpi.com/1873-149X/29/3/33/htm (Full text)

Histamine production by the gut microbiota induces visceral hyperalgesia through histamine 4 receptor signaling in mice

Abstract:

The gut microbiota has been implicated in chronic pain disorders, including irritable bowel syndrome (IBS), yet specific pathophysiological mechanisms remain unclear. We showed that decreasing intake of fermentable carbohydrates improved abdominal pain in patients with IBS, and this was accompanied by changes in the gut microbiota and decreased urinary histamine concentrations.

Here, we used germ-free mice colonized with fecal microbiota from patients with IBS to investigate the role of gut bacteria and the neuroactive mediator histamine in visceral hypersensitivity. Germ-free mice colonized with the fecal microbiota of patients with IBS who had high but not low urinary histamine developed visceral hyperalgesia and mast cell activation. When these mice were fed a diet with reduced fermentable carbohydrates, the animals showed a decrease in visceral hypersensitivity and mast cell accumulation in the colon. We observed that the fecal microbiota from patients with IBS with high but not low urinary histamine produced large amounts of histamine in vitro.

We identified Klebsiella aerogenes, carrying a histidine decarboxylase gene variant, as a major producer of this histamine. This bacterial strain was highly abundant in the fecal microbiota of three independent cohorts of patients with IBS compared with healthy individuals. Pharmacological blockade of the histamine 4 receptor in vivo inhibited visceral hypersensitivity and decreased mast cell accumulation in the colon of germ-free mice colonized with the high histamine-producing IBS fecal microbiota. These results suggest that therapeutic strategies directed against bacterial histamine could help treat visceral hyperalgesia in a subset of patients with IBS with chronic abdominal pain.

Source: De Palma G, Shimbori C, Reed DE, Yu Y, Rabbia V, Lu J, Jimenez-Vargas N, Sessenwein J, Lopez-Lopez C, Pigrau M, Jaramillo-Polanco J, Zhang Y, Baerg L, Manzar A, Pujo J, Bai X, Pinto-Sanchez MI, Caminero A, Madsen K, Surette MG, Beyak M, Lomax AE, Verdu EF, Collins SM, Vanner SJ, Bercik P. Histamine production by the gut microbiota induces visceral hyperalgesia through histamine 4 receptor signaling in mice. Sci Transl Med. 2022 Jul 27;14(655):eabj1895. doi: 10.1126/scitranslmed.abj1895. Epub 2022 Jul 27. PMID: 35895832. https://pubmed.ncbi.nlm.nih.gov/35895832/

Histamine-producing gut bacteria can trigger chronic abdominal pain

Press Release: Hamilton, ON (July 27, 2022) – Researchers from McMaster University and Queen’s University have discovered a gut bacterial ‘super-producer’ of histamine that can cause pain flare-ups in some patients with irritable bowel syndrome (IBS).

The culprit is what has now been named Klebsiella aerogenes, the McMaster-Queen (MQ) strain, identified in up to 25 per cent of gut microbiota samples from patients with IBS. Researchers examined stool microbiota samples from both Canadian and American patient cohorts.

“We followed up these patients for several months and found high levels of stool histamine at the time when the patients reported severe pain, and low stool histamine when they were pain-free,” said senior author Premysl Bercik, professor of medicine of McMaster’s Michael G. DeGroote School of Medicine and a gastroenterologist.

The McMaster-Queen’s research team pinpointed the bacterium Klebsiella aerogenes as the key histamine producer by studying germ-free mice colonized with gut microbiota from patients with IBS. They also colonized some mice with gut microbiota from healthy volunteers as a control group.

The study found that the bacterium Klebsiella aerogenes converts dietary histidine, an essential amino acid present in animal and plant protein, into histamine, a known mediator of pain.

The bacterial histamine then activates the gut immune system through histamine-4 receptor, which draws immune mast cells into the intestines. These activated mast cells produce even more histamine and other pain-signalling mediators, triggering inflammation and pain.

“Now that we know how the histamine is produced in the gut, we can identify and develop therapies that target the histamine producing bacteria,” said first author Giada de Palma, assistant professor of medicine at McMaster.

The study found that when the mice colonized with histamine producing bacteria were fed a diet low in fermentable carbohydrates, bacterial histamine production dramatically decreased. This was due to change in bacterial fermentation and acidity within the gut, which inhibited the bacterial enzyme responsible for histamine production.

Bercik said that these results explain the beneficial effects of a low fermentable diet observed in patients with IBS.

It is known that patients with IBS have more mast cells in their intestines, and that some of them improve with treatments targeting mast cells or histamine, such as mast cell stabilizers or antihistamines.

“Although mast cell treatment in IBS has been explored, a novel approach based on our research would be targeting the bacterial histamine production or H4R pathways,” Bercik said.

The McMaster-Queen’s study explains why increased mast cells are found in IBS and suggests that H4 receptor pathway plays a major role in this process.

“If we block the H4 receptors, then we can prevent recruitment of mast cells to the colon and subsequently the development of abdominal pain,” said senior co-author Stephen Vanner, professor of medicine at Queen’s University.

“Many but not all IBS patients will benefit from therapies targeting this histamine driven pathway,” said co-first author David Reed, assistant professor of medicine at Queen’s. Reed said that one or more biomarkers of this pathway could be used to find the patients most likely to benefit.

The McMaster-Queens study was funded by the Canadian Institutes of Health Research.

The study was published in the journal Science Translational Medicine on July 27.

Click HERE to read the study.

 

Assessing sleep and pain among adults with myalgic encephalomyelitis/chronic fatigue syndrome: psychometric evaluation of the PROMIS® sleep and pain short forms

Abstract:

Purpose: To evaluate the psychometric properties of the patient-reported outcome measurement information system® (PROMIS) short forms for assessing sleep disturbance, sleep-related impairment, pain interference, and pain behavior, among adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Methods: Data came from the Multi-Site ME/CFS study conducted between 2012 and 2020 at seven ME/CFS specialty clinics across the USA. Baseline and follow-up data from ME/CFS and healthy control (HC) groups were used to examine ceiling/floor effects, internal consistency reliability, differential item functioning (DIF), known-groups validity, and responsiveness.

Results: A total of 945 participants completed the baseline assessment (602 ME/CFS and 338 HC) and 441 ME/CFS also completed the follow-up. The baseline mean T-scores of PROMIS sleep and pain measures ranged from 57.68 to 62.40, about one standard deviation above the national norm (T-score = 50). All four measures showed high internal consistency (ω = 0.92 to 0.97) and no substantial floor/ceiling effects. No DIF was detected by age or sex. Known-groups comparisons among ME/CFS groups with low, medium, and high functional impairment showed significant small-sized differences in scores (η2 = 0.01 to 0.05) for the two sleep measures and small-to-medium-sized differences (η2 = 0.01 to 0.15) for the two pain measures. ME/CFS participants had significantly worse scores than HC (η2 = 0.35 to 0.45) for all four measures. Given the non-interventional nature of the study, responsiveness was evaluated as sensitivity to change over time and the pain interference measure showed an acceptable sensitivity.

Conclusion: The PROMIS sleep and pain measures demonstrated satisfactory psychometric properties supporting their use in ME/CFS research and clinical practice.

Source: Yang M, Keller S, Lin JS. Assessing sleep and pain among adults with myalgic encephalomyelitis/chronic fatigue syndrome: psychometric evaluation of the PROMIS® sleep and pain short forms. Qual Life Res. 2022 Jul 27. doi: 10.1007/s11136-022-03199-8. Epub ahead of print. PMID: 35896905.  https://pubmed.ncbi.nlm.nih.gov/35896905/