Food Implications in Central Sensitization Syndromes

Abstract:

Fibromyalgia (FM), chronic fatigue syndrome (CFS) and multiple chemical sensitivity (MCS) are some of the central sensitization syndromes (CSSs). The complexity of their diagnosis, the high interindividual heterogeneity and the existence of multi-syndromic patients requires a multifaceted treatment. The scientific literature is contradictory regarding the role of food in CSS, and evidence on the role of nutrition in MCS is particularly scarce. This review consists in gathering information about the current status of dietary recommendations (i.e., special dietary interventions, the role of additives, presence of micronutrient deficiencies, nutritional supplements and elimination of other nutrients and substances) and discussing the scientific evidence in depth to shed light on appropriate nutritional treatment managements for CSS patients. Current indications show that dietary modifications may vastly improve the patients’ quality of life at a low cost. We suggest personalized treatment, taking into consideration the severity of the disease symptoms, quality of life, coexistence with other diseases, pharmacological treatment, changing clinical characteristics, nutritional status, energy requirements and food tolerances, among others, as the best ways to tailor specific dietary interventions. These approaches will partially overcome the lack of scientific and clinical research on MSC. Patients should also be advised on the serious consequences of following dietary guidelines without a dietitian’s and clinician’s supervision.

Source: Aguilar-Aguilar E, Marcos-Pasero H, Ikonomopoulou MP, Loria-Kohen V. Food Implications in Central Sensitization Syndromes. J Clin Med. 2020 Dec 19;9(12):E4106. doi: 10.3390/jcm9124106. PMID: 33352747. https://pubmed.ncbi.nlm.nih.gov/33352747/

High Prevalence of Perineural Cysts in Patients with Fibromyalgia and Chronic Fatigue Syndrome

Abstract:

Objective: Pain in fibromyalgia (FM) and chronic fatigue syndrome (CFS) is assumed to originate from central sensitization. Perineural cysts or Tarlov cysts (TCs) are nerve root dilations resulting from pathologically increased cerebrospinal fluid pressure. These cysts initially affect sensory neurons and axons in dorsal root ganglia and produce sensory symptoms (pain and paresthesia). Symptomatic TC (STC) patients often complain about widespread pain and fatigue. Consequently, STC patients may initially be diagnosed with FM, CFS, or both. The objective of this study was to document the prevalence of TCs in patients diagnosed with FM or CFS.

Design: A retrospective study.

Setting: An outpatient clinic for musculoskeletal disorders.

Subjects: Patients diagnosed with FM according to the 1990 American College of Rheumatology criteria or with CFS according to the 1994 Centers for Disease Control criteria were selected.

Methods: Review of lumbar and sacral magnetic resonance imaging scans including TCs ≥5 mm in size.

Results: In total, 197 patients with FM, CFS, or both underwent magnetic resonance imaging. Ninety-one percent were women. The mean age was 48.1 (±11.9) years. TCs were observed in 39% of patients, with a mean size of 11.8 (±5.2) mm. In males, the prevalence was 12%, vs. 42% in females.

Conclusions: In patients diagnosed with FM or CFS, the prevalence of TCs was three times higher than that in the general population. This observation supports the hypothesis that STCs, FM, and CFS may share the same pathophysiological mechanism, i.e., moderately increased cerebrospinal fluid pressure, causing irritation of neurons and axons in dorsal root ganglia.

Source: Hulens M, Bruyninckx F, Dankaerts W, Rasschaert R, De Mulder P, Stalmans I, Vansant G, Bervoets C. High Prevalence of Perineural Cysts in Patients with Fibromyalgia and Chronic Fatigue Syndrome. Pain Med. 2020 Dec 1:pnaa410. doi: 10.1093/pm/pnaa410. Epub ahead of print. PMID: 33260218. https://pubmed.ncbi.nlm.nih.gov/33260218/

The Interplay between Oxidative Stress, Exercise, and Pain in Health and Disease: Potential Role of Autonomic Regulation and Epigenetic Mechanisms

Abstract:

Oxidative stress can be induced by various stimuli and altered in certain conditions, including exercise and pain. Although many studies have investigated oxidative stress in relation to either exercise or pain, the literature presents conflicting results. Therefore, this review critically discusses existing literature about this topic, aiming to provide a clear overview of known interactions between oxidative stress, exercise, and pain in healthy people as well as in people with chronic pain, and to highlight possible confounding factors to keep in mind when reflecting on these interactions. In addition, autonomic regulation and epigenetic mechanisms are proposed as potential mechanisms of action underlying the interplay between oxidative stress, exercise, and pain.

This review highlights that the relation between oxidative stress, exercise, and pain is poorly understood and not straightforward, as it is dependent on the characteristics of exercise, but also on which population is investigated. To be able to compare studies on this topic, strict guidelines should be developed to limit the effect of several confounding factors. This way, the true interplay between oxidative stress, exercise, and pain, and the underlying mechanisms of action can be revealed and validated via independent studies.

Source: Hendrix J, Nijs J, Ickmans K, Godderis L, Ghosh M, Polli A. The Interplay between Oxidative Stress, Exercise, and Pain in Health and Disease: Potential Role of Autonomic Regulation and Epigenetic Mechanisms. Antioxidants (Basel). 2020 Nov 23;9(11):1166. doi: 10.3390/antiox9111166. PMID: 33238564; PMCID: PMC7700330. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700330/  (Full text)

Fibromyalgia and Chronic Fatigue Syndrome in the Age of COVID-19

Excerpt:

It has been demonstrated that clinical outcomes of COVID-19 are significantly worse in persons with advanced age and those with “traditional” medical comorbidities (cardiovascular disease, pulmonary disease, diabetes, malignancy, and immunosuppression). But what about the ever-increasing group of people in our society, many of whom do not have “traditional” medical comorbidities, who suffer chronically from pain, fatigue, and functional decline? We are referring to patients with fibromyalgia (FM) and chronic fatigue syndrome (CFS): 2 conditions that, although medically distinct, share a common pathophysiological etiology: central sensitization (CS)., , , 

Source: Mohabbat AB, Mohabbat NML, Wight EC. Fibromyalgia and Chronic Fatigue Syndrome in the Age of COVID-19. Mayo Clin Proc Innov Qual Outcomes. 2020 Nov 13. doi: 10.1016/j.mayocpiqo.2020.08.002. Epub ahead of print. PMID: 33204998; PMCID: PMC7661943. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661943/ (Full text)

The antinuclear antibody dense fine speckled pattern and possible clinical associations: An indication of a proinflammatory microenvironment

Abstract:

Background: Indirect immunofluorescence (IIF) is the most prevalent screening antinuclear antibody test for systemic autoimmune rheumatic disease (SARD). Certain IIF patterns have known antibody and disease associations, but the dense fine speckled (ANA-DFS) pattern has no confirmed clinical associations. Our objective was to determine the prevalence of SARD among a group of ANA-DFS positive individuals and to identify final diagnoses among non-SARD individuals in order to determine possible clinical associations with the ANA-DFS pattern.

Methods: A retrospective study of 425 patients from a university health care system with a positive ANA-DFS pattern consecutively between August 2017 and September 2018. Sera samples underwent ANA testing by IIF on HEp-2 cell substrates (Euroimmun, Germany). Clinical information was retrieved from electronic health records and stored in a de-identified database.

Results: The prevalence of SARD was 24%. Undetermined diagnosis (17%), skin disorders (12.1%), and fibromyalgia/chronic pain syndrome/chronic fatigue syndrome (11.8%) were the most common non-SARD diagnoses. Taking into account past medical history, the most common non-SARD were atopic disorders (21.2%), fibromyalgia/chronic pain syndrome/chronic fatigue syndrome (17.6%), and skin disorders (16.7%).

Conclusions: The ANA-DFS pattern may be indicative of an underlying antigen-antibody interaction that plays a role in either the initiation or propagation of immunologic reactions. DFS70/LEDGF is a transcription factor involved in cell survival and stress protection, and autoantibodies may inhibit its function. It is likely that there are other antibodies producing the ANA-DFS pattern besides anti-DFS70/LEDGF, and more research is necessary to identify additional antibody specificities. The ANA-DFS pattern may be an indicator of a proinflammatory microenvironment given the high frequency of symptomatic patients and disease processes with an immunologic basis (including SARD).

Source: Lundgren MC, Sapkota S, Peterson DJ, Crosson JT. The antinuclear antibody dense fine speckled pattern and possible clinical associations: An indication of a proinflammatory microenvironment. J Immunol Methods. 2020 Oct 26:112904. doi: 10.1016/j.jim.2020.112904. Epub ahead of print. PMID: 33121975. https://pubmed.ncbi.nlm.nih.gov/33121975/

Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Abstract:

Introduction: In a large study with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients, we showed that 86% had symptoms of orthostatic intolerance in daily life and that 90% had an abnormal reduction in cerebral blood flow (CBF) during a standard tilt test. A standard head-up tilt test might not be tolerated by the most severely affected bed-ridden ME/CFS patients. Sitting upright is a milder orthostatic stress. The present study examined whether a sitting test, measuring cerebral blood flow by extracranial Doppler, would be sufficient to provoke abnormal reductions in cerebral blood flow in severe ME/CFS patients.

Methods and results: 100 severe ME/CFS patients were studied, (88 females) and were compared with 15 healthy controls (HC) (13 females). CBF was measured first while seated for at least one hour, followed by a CBF measurement in the supine position. Fibromyalgia was present in 37 patients. Demographic data as well as supine heart rate and blood pressures were not different between ME/CFS patients and HC. Heart rate and blood pressure did not change significantly between supine and sitting both in patients and HC. Supine CBF was not different between patients and HC. In contrast, absolute CBF during sitting was lower in patients compared to HC: 474 (96) mL/min in patients and 627 (89) mL/min in HC; p < 0.0001. As a result, percent CBF reduction while seated was −24.5 (9.4)% in severe ME/CFS patients and −0.4 (1.2)% in HC (p < 0.0001). In the ten patients who had no orthostatic intolerance complaints in daily life, the CBF reduction was −2.7 (2.1)%, which was not significantly different from HC (p = 0.58). The remaining 90 patients with orthostatic intolerance complaints had a −26.9 (6.2)% CBF reduction. No difference in CBF parameters was found in patients with and without fibromyalgia. Patients with a previous diagnosis of postural orthostatic tachycardia syndrome (POTS) had a significantly larger CBF reduction compared with those without POTS: 28.8 (7.2)% vs. 22.3 (9.7)% (p = 0.0008).

Conclusions: A sitting test in severe ME/CFS patients was sufficient to provoke a clinically and statistically significant mean CBF decline of 24.5%. Patients with a previous diagnosis of POTS had a larger CBF reduction while seated, compared to patients without POTS. The magnitude of these CBF reductions is similar to the results in less severely affected ME/CFS patients during head-up tilt, suggesting that a sitting test is adequate for the diagnosis of orthostatic intolerance in severely affected patients.

Source: C (Linda) MC van Campen, Peter C. Rowe, and Frans C Visser. Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Healthcare 2020, 8(4), 394; https://doi.org/10.3390/healthcare8040394 https://www.mdpi.com/2227-9032/8/4/394/htm (Full text)

Predictors of New Onsets of Irritable Bowel Syndrome, Chronic Fatigue Syndrome and Fibromyalgia: The Lifelines Study

Abstract:

Background: It has been claimed that functional somatic syndromes share a common etiology. This prospective population-based study assessed whether the same variables predict new onsets of irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS) and fibromyalgia (FM).

Methods: The study included 152 180 adults in the Dutch Lifelines study who reported the presence/absence of relevant syndromes at baseline and follow-up. They were screened at baseline for physical and psychological disorders, socio-demographic, psycho-social and behavioral variables. At follow-up (mean 2.4 years) new onsets of each syndrome were identified by self-report. We performed separate analyses for the three syndromes including participants free of the relevant syndrome or its key symptom at baseline. LASSO logistic regressions were applied to identify which of the 102 baseline variables predicted new onsets of each syndrome.

Results: There were 1595 (1.2%), 296 (0.2%) and 692 (0.5%) new onsets of IBS, CFS, and FM, respectively. LASSO logistic regression selected 26, 7 and 19 predictors for IBS, CFS and FM, respectively. Four predictors were shared by all three syndromes, four predicted IBS and FM and two predicted IBS and CFS but 28 predictors were specific to a single syndrome. CFS was more distinct from IBS and FM, which predicted each other.

Conclusions: Syndrome-specific predictors were more common than shared ones and these predictors might form a better starting point to unravel the heterogeneous etiologies of these syndromes than the current approach based on symptom patterns. The close relationship between IBS and FM is striking and requires further research.

Source: Monden R, Rosmalen JGM, Wardenaar KJ, Creed F. Predictors of new onsets of irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia: the lifelines study [published online ahead of print, 2020 Jun 17]. Psychol Med. 2020;1-9. doi:10.1017/S0033291720001774 https://pubmed.ncbi.nlm.nih.gov/32546287/

DNA Methylation and BDNF Expression Account for Symptoms and Widespread Hyperalgesia in Patients With Chronic Fatigue Syndrome and Fibromyalgia

Abstract:

Background: Epigenetics of neurotrophic factors holds the potential to unravel the mechanisms underlying the pathophysiology of complex conditions such as chronic fatigue syndrome (CFS). This study explored the role of brain-derived neurotrophic factor (BDNF) genetics, epigenetics, and protein expression in patients with both CFS and comorbid fibromyalgia (CFS/FM).

Methods: A repeated-measures study in 54 participants (28 patients with CFS/FM and 26 matched healthy controls) was conducted. Participants underwent a comprehensive assessment, including questionnaires, sensory testing, and blood withdrawal. BDNF protein level was measured in serum (sBDNF) using ELISA, while polymorphism and DNA methylation were measured in blood, using pyrosequencing technology. To assess temporal stability of the measures, participants underwent the same assessment twice within four days.

Results: Repeated-measures mixed linear models were performed for between-group analysis. sBNDF was higher in patients with CFS/FM (F=15.703; mean difference: 3.31 ng/ml, 95% C.I. 1.65 to 4.96; p=.001), whereas BDNF DNA methylation was lower in Exon IX (F=9.312; mean difference -2.38%, C.I. -3.93 to -0.83; p=.003). BDNF DNA methylation was mediated by the Val66Met (rs6265) polymorphism. Lower methylation in the same region predicted higher sBDNF (F=4.910, t= -2.216, p=.029, 95% C.I. = -.712 to -.039) which in turn predicted participants’ symptoms (F=14.410, t= 3.796, 95% C.I.= 1.79 to 5.71, p=.001) and widespread hyperalgesia (F=4.147, t= 2.036, 95% C.I.= .01 to .08, p=.044).

Discussion: sBDNF is higher in patients with CFS/FM and BDNF methylation in exon IX accounts for regulating protein expression. Altered BDNF might represent a key mechanism explaining CFS/FM pathophysiology.

Source: Polli A, Ghosh M, Bakusic J, et al. DNA methylation and BDNF expression account for symptoms and widespread hyperalgesia in patients with Chronic Fatigue Syndrome and Fibromyalgia [published online ahead of print, 2020 Jun 20]. Arthritis Rheumatol. 2020;10.1002/art.41405. doi:10.1002/art.41405 https://pubmed.ncbi.nlm.nih.gov/32562379/

Chronic Pain Syndromes and Their Laryngeal Manifestations

Abstract:

IMPORTANCE: Fibromyalgia syndrome (FMS), irritable bowel syndrome (IBS), and chronic fatigue syndrome (CFS) are traditionally considered as distinct entities grouped under chronic pain syndrome (CPS) of an unknown origin. However, these 3 disorders may exist on a spectrum with a shared pathophysiology.

OBJECTIVE: To investigate whether the clinical presentation of FMS, IBS, and CFS is similar in a population presenting with voice and laryngeal disorders.

DESIGN, SETTING, AND PARTICIPANTS: This case series was a retrospective review of the medical records and clinical notes of patients treated between January 1, 2016, and December 31, 2017, at the Johns Hopkins Voice Center in Baltimore, Maryland. Patients with at least 1 CPS of interest (FMS, IBS, or CFS) were included (n = 215), along with patients without such diagnoses (n = 4034). Diagnoses, demographic, and comorbidity data were reviewed. Diagnoses related to voice and laryngeal disorders were subdivided into 5 main categories (laryngeal pathology, functional voice disorders, airway problems, swallowing problems, and other diagnoses).

MAIN OUTCOMES AND MEASURES: Prevalence and odds ratios of 45 voice and laryngeal disorders were reviewed. Odds ratios (ORs) were calculated by comparing patients with CPS with control patients.

RESULTS: In total, 4249 individuals were identified; 215 (5.1%) had at least 1 CPS and 4034 (94.9%) were control participants. Patients with CPS were 3 times more likely to be women compared with the control group (173 of 215 [80.5%] vs 2318 of 4034 [57.5%]; OR, 3.156; 95% CI, 2.392-4.296), and the CPS group had a mean (SD) age of 57.80 (15.30) years compared with the mean (SD) age of 55.77 (16.97) years for the control group. Patients with CPS were more likely to present with functional voice disorders (OR, 1.812; 95% CI, 1.396-2.353) and less likely to present with laryngeal pathology (OR, 0.774; 95% CI, 0.610-0.982) or airway problems (OR, 0.474; 95% CI, 0.285-0.789).

CONCLUSIONS AND RELEVANCE: The voice and airway presentation of patients with FMS, IBS, and/or CFS appears to be indistinguishable from each other. This finding suggests that these 3 diseases share upper airway symptoms.

Source: Piersiala K, Akst LM, Hillel AT, Best SR. Chronic Pain Syndromes and Their Laryngeal Manifestations. JAMA Otolaryngol Head Neck Surg. 2020 Apr 30. doi: 10.1001/jamaoto.2020.0530. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32352483

Systemic Hyperalgesia in Females with Gulf War Illness, Chronic Fatigue Syndrome and Fibromyalgia

Abstract:

Pain is a diagnostic criterion for Gulf War Illness (GWI), Chronic Fatigue Syndrome (CFS), and fibromyalgia (FM). The physical sign of systemic hyperalgesia (tenderness) was assessed in 920 women who were stratified by 2000 Kansas GWI, 1994 CFS, and 1990 FM criteria.

Pressure was applied by dolorimetry at 18 traditional tender points and the average pressure causing pain determined. GWI women were the most tender (2.9 ± 1.6 kg, mean ± SD, n = 70), followed by CFS/FM (3.1 ± 1.4 kg, n = 196), FM (3.9 ± 1.4 kg, n = 56), and CFS (5.8 ± 2.1 kg, n = 170) compared to controls (7.2 ± 2.4 kg, significantly highest by Mann-Whitney tests p < 0.0001, n = 428). Receiver operating characteristics set pressure thresholds of 4.0 kg to define GWI and CFS/FM (specificity 0.85, sensitivities 0.80 and 0.83, respectively), 4.5 kg for FM, and 6.0 kg for CFS.

Pain, fatigue, quality of life, and CFS symptoms were equivalent for GWI, CFS/FM and CFS. Dolorimetry correlated with symptoms in GWI but not CFS or FM. Therefore, women with GWI, CFS and FM have systemic hyperalgesia compared to sedentary controls.

The physical sign of tenderness may complement the symptoms of the Kansas criteria as a diagnostic criterion for GWI females, and aid in the diagnosis of CFS. Molecular mechanisms of systemic hyperalgesia may provide new insights into the neuropathology and treatments of these nociceptive, interoceptive and fatiguing illnesses.

Source: Surian AA, Baraniuk JN. Systemic Hyperalgesia in Females with Gulf War Illness, Chronic Fatigue Syndrome and Fibromyalgia. Sci Rep. 2020 Apr 1;10(1):5751. doi: 10.1038/s41598-020-62771-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113257/ (Full text)