Las manifestaciones primordiales de la fibromialgia, dolor generalizado e insomnio, en la pintura de Remedios Varo / Fibromyalgia's main features, widespread pain, and insomnia in the paintings of Remedios Varo

La sensibilidad de las artistas plásticas ante el sufrimiento humano ha quedado plasmada de diversas maneras. Este artículo relata las circunstancias que llevaron a la pintora surrealista hispano-mexicana, Remedios Varo, a representar en forma original las 2 manifestaciones cardinales de la fibromialgia: dolor generalizado e insomnio. (AU)

The sensitivity of plastic artists to human suffering has been expressed in different ways. This article recounts the circumstances that led the Spanish-Mexican surrealist painter, Remedios Varo, to depict in an original way the 2 cardinal manifestations of fibromyalgia; widespread pain and insomnia. (AU)

Hypothetical framework for post-COVID 19 condition based on a fibromyalgia pathogenetic model.

There is a clear clinical overlap between fibromyalgia, myalgic encephalomyelitis, and post-COVID 19 condition. Chronic fatigue, cognitive impairment, and widespread pain characterize these 3 syndromes. A steady line of investigation posits fibromyalgia as stress-evoked sympathetically maintained neuropathic pain syndrome and places dorsal root ganglia dysregulation with the ensuing small fiber neuropathy at the epicenter of fibromyalgia pathogenesis. This article discusses emerging evidence suggesting that similar mechanism may operate in post-COVID 19 condition.

Fibromyalgia's main features, widespread pain, and insomnia in the paintings of Remedios Varo.

The sensitivity of plastic artists to human suffering has been expressed in different ways. This article recounts the circumstances that led the Spanish-Mexican surrealist painter, Remedios Varo, to depict in an original way the two cardinal manifestations of fibromyalgia; widespread pain and insomnia.

The value of inquiring patients about local discomfort during blood pressure measurement for fibromyalgia detection. A cross-sectional study.

BACKGROUND: Fibromyalgia overlaps and/or mimics other rheumatic diseases and may be a confounding factor in the clinimetric assessment of these illnesses. Allodynia is a distinctive fibromyalgia feature that can be elicited during routine blood pressure measurement. For epidemiological purposes fibromyalgia can be diagnosed using the 2016 Wolfe et al. criteria questionnaire. No physical examination is required. OBJECTIVE: To evaluate the role of a straightforward question formulated during routine blood pressure measurement for fibromyalgia detection in a rheumatology outpatient clinic. PATIENTS AND METHODS: All adult patients attending our Rheumatology outpatient clinic were invited to participate. While awaiting their medical consultation, they filled-out the 2016 Wolfe et al. FM diagnostic criteria questionnaire. During the ensuing routine physical examination, the physician advanced the following guideline: "I am going to take your blood pressure; tell me if the cuff's pressure causes pain". Then, blood pressure cuff was inflated to 170 mm/Hg. Sphygmomanometry induced allodynia was defined as any local discomfort caused by blood pressure measurement. If a patient voiced any uneasiness, a follow-up dichotomic question was formulated "did it hurt much or little". Sphygmomanometry-induced allodynia was correlated with the presence of fibromyalgia according to the 2016 Wolfe diagnostic criteria. RESULTS: Four hundred and ninety-one patients were included in the study; most of them (84%) were female. The female cohort displayed the following features: Twenty five percent had fibromyalgia. Twenty seven percent had sphygmomanometry-induced allodynia. In women, sphygmomanometry-evoked allodynia had 63% sensitivity and 84% specificity for fibromyalgia diagnosis. The area under curve was 0.751. Moreover, having "much" local pain elicitation during blood pressure testing had 23% sensitivity and 96% specificity for fibromyalgia diagnosis. Men behaved differently; 15% fulfilled the fibromyalgia diagnostic criteria, but only 2% had sphygmomanometry induced allodynia. CONCLUSIONS: Inquiring female patients about local discomfort during routine blood pressure measurement is a simple and efficient procedure for fibromyalgia detection. This undemanding approach could be implemented in all clinical settings. There is marked sexual dimorphism in the link between sphygmomanometry-induced allodynia and fibromyalgia diagnosis. The presence of fibromyalgia is almost certain in those individuals having substantial pain elicitation during blood pressure measurement.

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) in 2023.

In 2011, a syndrome entitled ASIA (Autoimmune/inflammatory Syndrome Induced by Adjuvants; Shoenfeld's syndrome) was first described. ASIA aimed to organize under a single umbrella, the existing evidence regarding certain environmental factors which possess immune stimulatory properties, in order to shed light on a common pathway of autoimmune pathogenesis. Such environmental immune stimulators, or adjuvants, include among others: aluminum salts as in vaccines, various medical implants, as well as various infectious agents. After the launch of the ASIA syndrome, the expansion and recognition of this syndrome by different researchers from different countries began. During the past decades, evidence had been accumulating that (auto)immune symptoms can be triggered by exposure to environmental immune stimulatory factors that act as an adjuvant in genetically susceptible individuals. A panoply of unexplained subjective and autonomic-related symptoms has been reported in patients with ASIA syndrome. The current review summarizes and updates accumulated knowledge from the past decades, describing new adjuvants- (e.g. polypropylene meshes) and vaccine- (e.g. HPV and COVID vaccines) induced ASIA. Furthermore, a direct association between inflammatory/autoimmune diseases with ASIA syndrome, will be discussed. Recent cases will strengthen some of the criteria depicted in ASIA syndrome such as clear improvement of symptoms by the removal of adjuvants (e.g. silicone breast implants) from the body of patients. Finally, we will introduce additional factors to be included in the criteria for ASIA syndrome such as: (1) dysregulated non-classical autoantibodies directed against G-protein coupled receptors (GPCRs) of the autonomic nervous system and (2)) small fiber neuropathy (SFN), both of which might explain, at least in part, the development of 'dysautonomia' reported in many ASIA patients.

Centralized nociplastic pain causing fibromyalgia: an emperor with no cloths?

The leading school of thought views fibromyalgia as a central sensitization syndrome. Nociplastic pain is the recently proposed term to mechanistically explain central sensitization. Accumulating research suggests an alternate explanation; fibromyalgia can be conceptualized as a neuropathic pain syndrome and dorsal root ganglia (not the brain) as the primary fibromyalgia pain source. There is no need to propose nociplastic pain as new chronic pain mechanism.

Clinical overlap between fibromyalgia and myalgic encephalomyelitis. A systematic review and meta-analysis.

Myalgic encephalomyelitis is an illness characterized by profound malaise after mental or physical effort occurring in patients already suffering from constant fatigue. On the other hand, widespread pain and widespread allodynia are the core fibromyalgia clinical features. There is controversy on these two syndromes alikeness. Through the years, different diagnostic and/or classification criteria have been put forward to appraise both fibromyalgia and myalgic encephalomyelitis. The epidemiology of these two illnesses, and their overlap, may vary accordingly to the used definition. The most recent Wolfe et al. 2016 fibromyalgia diagnostic criteria incorporates three myalgic encephalomyelitis features including fatigue, waking unrefreshed and dyscognition. The objective of this meta-analysis was to define the clinical overlap between fibromyalgia and myalgic encephalomyelitis based on a systematic literature review. METHODS: PubMed, Embase, Lilacs, and Cochrane data bases were searched on January 25, 2021 linking the medical subject heading "Fibromyalgia" to the following terms "chronic fatigue syndrome", "myalgic encephalomyelitis" and "systemic exertion intolerance disease". Our review included all original articles in which the clinical overlap between fibromyalgia and myalgic encephalomyelitis could be quantified based on recognized diagnostic or classification criteria. Articles scrutiny and selection followed the PRISMA guidelines. Each study quality was assessed according to GRADE recommendations. The global clinical overlap was calculated using a fixed effect model with inverse variance-weighted average method. RESULTS: Twenty one publications were included in the meta-analysis. Reviewed studies were highly dissimilar in their design, objectives, sample size, diagnostic criteria, and/or outcomes yielding a 98% heterogeneity index. Nevertheless, the clinical overlap between fibromyalgia and myalgic encephalomyelitis was a well defined outcome that could be reliably calculated despite the high heterogeneity value. All reviewed publications had moderate GRADE evidence level. Most evaluated articles used the old 1990 Wolfe et al. fibromyalgia diagnostic criteria. Myalgic encephalomyelitis and fibromyalgia diagnoses overlapped in 47.3% (95% CI: 45.97-48.63) of the reported cases. CONCLUSION: This meta-analysis found prominent clinical overlap between fibromyalgia and myalgic encephalomyelitis. It seems likely that this concordance would be even higher when using the most recent Wolfe et al. 2016 fibromyalgia diagnostic criteria.

Dorsal root ganglia: fibromyalgia pain factory?

This perspective article focuses on dorsal root ganglia (DRG) as potential fibromyalgia main pain source. Humans possess 31 pairs of DRG lying along the spine. These ganglia have unique anatomical and physiological features. During development, DRG are extruded from the central nervous system and from the blood-brain barrier but remain surrounded by meningeal layers and by cerebrospinal fluid. DRG house the pain-transmitting small nerve fiber nuclei; each individual nucleus is tightly enveloped by metabolically active glial cells. DRG possess multiple inflammatory/pro-nociceptive molecules including ion channels, neuropeptides, lymphocytes, and macrophages. DRG neurons have pseudo-unipolar structure making them able to generate pain signals; additionally, they can sequester antigen-specific antibodies thus inducing immune-mediated hyperalgesia. In rodents, diverse physical and/or environmental stressors induce DRG phenotypic changes and hyperalgesia. Unfolding clinical evidence links DRG pathology to fibromyalgia and similar syndromes. Severe fibromyalgia is associated to particular DRG ion channel genotype. Myalgic encephalomyelitis patients with comorbid fibromyalgia have exercise-induced DRG pro-nociceptive molecules gene overexpression. Skin biopsy demonstrates small nerve fiber pathology in approximately half of fibromyalgia patients. A confocal microscopy study of fibromyalgia patients disclosed strong correlation between corneal denervation and small fiber neuropathy symptom burden. DRG may be fibromyalgia neural hub where different stressors can be transformed in neuropathic pain. Novel neuroimaging technology and postmortem inquest may better define DRG involvement in fibromyalgia and similar maladies. DRG pro-nociceptive molecules are attractive fibromyalgia therapeutic targets.

Complex Regional Pain Syndrome Evolving to Full-Blown Fibromyalgia: A Proposal of Common Mechanisms.

BACKGROUND: Spread of complex regional pain syndrome (CRPS) outside the affected limb is a well-recognized phenomenon; nevertheless, the actual evolution from CRPS to fibromyalgia is poorly documented. Similar mechanisms have been recently put forward to explain the development of CRPS and fibromyalgia including dorsal root ganglia (DRG) hyperexcitability and small fiber neuropathy. OBJECTIVES: The aims of this study were to describe 3 cases with typical CRPS evolving to full-blown fibromyalgia and to discuss the potential pathogenetic mechanisms linking these debilitating illnesses. METHODS: This was a review of medical records and PubMed search on the relationship between CRPS-fibromyalgia with DRG and small nerve fiber neuropathy. RESULTS: Our 3 cases displayed over time orderly evolution from CRPS to fibromyalgia. Dorsal root ganglion hyperexcitability and small fiber neuropathy have been recently demonstrated in CRPS and in fibromyalgia. Dorsal root ganglia contain the small nerve fiber cell bodies surrounded by glial cells. After trauma, DRG perineuronal glial cells produce diverse proinflammatory mediators. Macrophages, lymphocytes, and satellite glial cells may drive the immune response to more rostrally and caudally located DRG and other spinal cord sites. Dorsal root ganglion metabolic changes may lead to small nerve fiber degeneration. This mechanism may explain the development of widespread pain and autonomic dysfunction. CONCLUSIONS: Clinicians should be aware that CRPS can evolve to full-blown fibromyalgia. Spreading of neuroinflammation through DRG glial cell activation could theoretically explain the transformation from regional to generalized complex pain syndrome.

Correlation Between Corneal Nerve Density and Symptoms of Small Fiber Neuropathy in Patients With Fibromyalgia: The Confounding Role of Severe Anxiety or Depression.

OBJECTIVE: A consistent line of investigation proposes fibromyalgia as a dysautonomia-associated neuropathic pain syndrome. Comorbid anxiety or depression amplifies fibromyalgia symptoms. The recent recognition of small fiber neuropathy in fibromyalgia patients supports the neuropathic nature of the illness. Corneal confocal microscopy accurately identifies small nerve fiber pathology. The newly developed Small-Fiber Symptom Survey captures the spectrum of small fiber neuropathy symptoms. We aimed to correlate corneal nerve density with different fibromyalgia disease severity questionnaires including the Small-Fiber Symptom Survey. We defined the possible confounding role of comorbid anxiety or depression severity in the clinical-pathological association. METHODS: This is a case series of 28 women with fibromyalgia. A single ophthalmologist quantified corneal subbasal plexus nerve density. Corneal innervation was correlated (Spearman ρ) with the following clinical questionnaires scores: Small-Fiber Symptom Survey, Revised Fibromyalgia Impact Questionnaire, and COMPASS-31 (Composite Autonomic Symptom Survey 31-Item Score). Validated inquiry forms assessed the comorbid anxiety and/or depression severity. RESULTS: There were no clinical-pathological correlations in the group as a whole. In the subgroup of fibromyalgia women without severe anxiety or depression (n = 13), there was a strong negative correlation between corneal nerve density with the Small-Fiber Symptom Survey score (ρ = -0.771, p = 0.002) and COMPASS-31 score (ρ = -0.648, p = 0.017). Patients with profound anxiety or depression (n = 15) had more intense symptoms but had not clinical-pathological correlations. CONCLUSIONS: Small fiber neuropathy and dysautonomia symptoms correlate with corneal denervation in women with fibromyalgia without severe anxiety or depression. This clinical-pathological association reinforces fibromyalgia as a dysautonomia-related neuropathic pain syndrome. Severe anxiety or depression distorts fibromyalgia symptoms. PRACTICAL POINT: Corneal confocal microscopy may become a useful procedure to study fibromyalgia patients.

Fibromyalgia in women: somatisation or stress-evoked, sex-dimorphic neuropathic pain?

Somatic symptom disorder is excessive anxiety towards persistent symptoms that do not have an identifiable physical origin. Fibromyalgia is a stress-related illness. The overwhelming majority of fibromyalgia patients seeking medical care are women. Most fibromyalgia sufferers fulfil the somatic symptom disorder diagnostic criteria. The objectives of this article are the following: 1) to examine fibromyalgia and somatic symptom disorder analogy. 2) to discuss stress-evoked neuropathic pain sexual dimorphism, and 3) to propose a neuropathic pathogenesis that may explain how stressed women could develop fibromyalgia. Recent research demonstrates a clear link between fibromyalgia and small fibre neuropathy. Dorsal root ganglia contain the small nerve fibre nuclei. In rodents, physical, chemical, or environmental stressors lead to dorsal root ganglia phenotypic changes and to hyperalgesia. This phenomenon is much more frequent in females. Prolactin, oestrogens, and progesterone alter dorsal root ganglia physiology, establishing abnormal connections between the stress response system and pain pathways. Rather than a mental somatic symptom disorder, fibromyalgia patients may have a stress-induced neuropathic pain syndrome. Sexually dimorphic dorsal root ganglia physiology may explain why it is women who more often develop fibromyalgia. Understanding fibromyalgia as a real stress-evoked neuropathic pain syndrome may lead to more compassionate patient care and may open new avenues for gender-related neuropathic pain investigation.

Gulf war illness, post-HPV vaccination syndrome, and Macrophagic Myofasciitis. Similar disabling conditions possibly linked to vaccine-induced autoimmune dysautonomia.

More than one-fourth of all Persian gulf war coalition soldiers remain seriously ill. Several epidemiological studies suggest a link between multiple vaccinations at the time of the military operation and the illness development. Macrophagic Myofasciitis and post-HPV vaccination syndrome are two newer controversial vaccine-related disabling ailments. OBJECTIVES: 1) To systematically review all original articles investigating the association of vaccines with gulf war illness, 2) To discuss gulf war illness, Macrophagic Myofasciitis, and post-HPV vaccination syndrome clinical similarities, 3) To discuss emergent pathogenetic mechanisms proposed for post-HPV vaccination syndrome that may be also relevant to gulf war illness and Macrophagic Myofasciitis. RESULTS: All original epidemiological studies (n = 11) found a positive association between vaccination and gulf war illness development. Chronic fatigue, widespread pain and cognitive impairment characterize the three syndromes under discussion. Anti-adrenergic receptor antibodies, dysautonomia and small fiber neuropathy have been recently described in patients with post-HPV vaccination syndrome. CONCLUSION: post-HPV vaccination syndrome, Macrophagic Myofasciitis, and gulf war illness analogy suggests that some vaccines or multiple vaccinations in a very short period of time may induce, in susceptible individuals, chronic pain, fatigue and dyscognition. Vaccine-induced autoimmune dysautonomia is hypothesized as the common pathogenetic mechanism for this symptom cluster. Further research on the presence of small fiber neuropathy, adrenergic receptor antibodies, and abnormal autonomic function tests in the three syndromes under discussion may help to elucidate this hypothesis.

Holistic Treatment of Fibromyalgia Based on Physiopathology: An Expert Opinion.

Patients suffering from fibromyalgia have many vexing symptoms; in contrast, physicians do not have a logical physiopathological framework to explain the multiple complaints. The objective of this writing is to discuss a patient-centered holistic fibromyalgia therapy based on a coherent physiopathological model.The rationale proposing fibromyalgia as stress-related sympathetically maintained neuropathic pain syndrome has solid research foundations. Autoimmunity is evident in a subset of fibromyalgia cases. Dorsal root ganglia are likely the crucial sympathetic-nociceptive short circuit sites. Skin biopsy and corneal confocal microscopy have demonstrated small nerve fiber pathology in fibromyalgia cases.Patient empowerment through information and symptom validation is the first step for a successful fibromyalgia therapy. POINTS TO HIGHLIGHT: Fibromyalgia is a genuine painful neuropathic pain syndrome. In fibromyalgia stress becomes pain. Autonomic (sympathetic) dysfunction explains the multiplicity of fibromyalgia symptoms.The well-informed patient (and her/his family) must take on the leading role in her/his own rehabilitation. Fibromyalgia treatment often requires important lifestyle changes. Physicians and allied health care personnel facilitate this adjustment. Specific fibromyalgia drivers are discussed. Common modern bad habits alter autonomic nervous system balance and worsen fibromyalgia symptoms. Currently used drugs for fibromyalgia are rudimentary and with low retention rates. Autoimmune fibromyalgia requires focused therapeutic approach. CONCLUSION: A patient-centered holistic therapy aimed to regain autonomic nervous system resilience remains the most effective fibromyalgia therapy. FUTURE DIRECTIONS: Corneal confocal microscopy will likely become an objective fibromyalgia diagnostic and follow-up procedure. More specific analgesic antineuropathic medications for fibromyalgia are on the horizon.