Nociplastic pain: towards an understanding of prevalent pain conditions

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ejp.1121

Efficacy, acceptability and safety of cognitive behavioural therapies in fibromyalgia syndrome - A systematic review and meta-analysis of randomized controlled trials.

Fibromyalgia (FM) is characterized by chronic widespread pain, unrefreshing sleep, physical exhaustion, and cognitive difficulties. It occurs in all populations throughout the world, with prevalence between 2% and 4% in general populations. Definition, pathogenesis, diagnosis, and treatment of FM remain points of contention, with some even contesting its existence. The various classification systems according to pain medicine, psychiatry, and neurology (pain disease; persistent somatoform pain disorder; masked depression; somatic symptom disorder; small fiber neuropathy; brain disease) mostly capture only some components of this complex and heterogeneous disorder. The diagnosis can be established in most cases by a general practitioner when the symptoms meet recognized criteria and a somatic disease sufficiently explaining the symptoms is excluded. Evidence-based interdisciplinary guidelines give a strong recommendation for aerobic exercise and cognitive behavioral therapies. Drug therapy is not mandatory. Only a minority of patients experience substantial symptom relief with duloxetine, milnacipran, and pregabalin.

/pdf/facts-and-myths-pertaining-to-fibromyalgia-2gcy5hjyu9.pdf

Facts and myths pertaining to fibromyalgia.

OBJECTIVE To assess patterns and impact of small nerve fiber dysfunction and pathology in patients with fibromyalgia syndrome (FMS). METHODS One hundred seventeen women with FMS underwent neurological examination, questionnaire assessment, neurophysiology assessment, and small fiber tests: skin punch biopsy, corneal confocal microscopy, microneurography, quantitative sensory testing including C-tactile afferents, and pain-related evoked potentials. Data were compared with those of women with major depressive disorder and chronic widespread pain (MD-P) and healthy women. RESULTS Intraepidermal nerve fiber density (IENFD) was reduced at different biopsy sites in 63% of FMS patients (MD-P: 10%, controls: 18%; p < 0.001 for each). We found 4 patterns of skin innervation in FMS: normal, distally reduced, proximally reduced, and both distally and proximally reduced (p < 0.01 for each compared to controls). Microneurography revealed initial activity-dependent acceleration of conduction velocity upon low frequencies of stimulation in 1A fibers, besides 1B fiber spontaneous activity and mechanical sensitization in FMS patients. FMS patients had elevated warm detection thresholds (p < 0.01), impaired C-tactile afferents (p < 0.05), and reduced amplitudes (p < 0.001) of pain-related evoked potentials compared to controls. Compared to FMS patients with normal skin innervation, those with generalized IENFD reduction had higher pain intensity and impairment due to pain, higher disease burden, more stabbing pain and paresthesias, and more anxiety (p < 0.05 for each). FMS patients with generalized IENFD reduction also had lower corneal nerve fiber density (p < 0.01) and length (p < 0.05). INTERPRETATION The extent of small fiber pathology is related to symptom severity in FMS. This knowledge may have implications for the diagnostic classification and treatment of patients with FMS. ANN NEUROL 2019;86:504-516.

/pdf/reduction-of-skin-innervation-is-associated-with-a-severe-4vf2x6miuw.pdf

Reduction of skin innervation is associated with a severe fibromyalgia phenotype

Background Fibromyalgia is a clinically defined chronic condition of unknown etiology characterized by chronic widespread pain that often co-exists with sleep disturbances, cognitive dysfunction and fatigue. People with fibromyalgia often report high disability levels and poor quality of life. Drug therapy, for example, with serotonin and noradrenaline reuptake inhibitors (SNRIs), focuses on reducing key symptoms and improving quality of life. This review updates and extends the 2013 version of this systematic review. Objectives To assess the efficacy, tolerability and safety of serotonin and noradrenaline reuptake inhibitors (SNRIs) compared with placebo or other active drug(s) in the treatment of fibromyalgia in adults. Search methods For this update we searched CENTRAL, MEDLINE, Embase, the US National Institutes of Health and the World Health Organization (WHO) International Clinical Trials Registry Platform for published and ongoing trials and examined the reference lists of reviewed articles, to 8 August 2017. Selection criteria We selected randomized, controlled trials of any formulation of SNRIs against placebo or any other active treatment of fibromyalgia in adults. Data collection and analysis Three review authors independently extracted data, examined study quality, and assessed risk of bias. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 50% or greater and of 30% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardized mean differences (SMD) for fatigue, sleep problems, health-related quality of life, mean pain intensity, depression, anxiety, disability, sexual function, cognitive disturbances and tenderness. For tolerability we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawals due to adverse events and for nausea, insomnia and somnolence as specific adverse events. For safety we calculated NNTH for serious adverse events. We undertook meta-analysis using a random-effects model. We assessed the evidence using GRADE and created a 'Summary of findings' table. Main results We added eight new studies with 1979 participants for a total of 18 included studies with 7903 participants. Seven studies investigated duloxetine and nine studies investigated milnacipran against placebo. One study compared desvenlafaxine with placebo and pregabalin. One study compared duloxetine with L-carnitine. The majority of studies were at unclear or high risk of bias in three to five domains.The quality of evidence of all comparisons of desvenlafaxine, duloxetine and milnacipran versus placebo in studies with a parallel design was low due to concerns about publication bias and indirectness, and very low for serious adverse events due to concerns about publication bias, imprecision and indirectness. The quality of evidence of all comparisons of duloxetine and desvenlafaxine with other active drugs was very low due to concerns about publication bias, imprecision and indirectness.Duloxetine and milnacipran had no clinically relevant benefit over placebo for pain relief of 50% or greater: 1274 of 4104 (31%) on duloxetine and milnacipran reported pain relief of 50% or greater compared to 591 of 2814 (21%) participants on placebo (risk difference (RD) 0.09, 95% confidence interval (CI) 0.07 to 0.11; NNTB 11, 95% CI 9 to 14). Duloxetine and milnacipran had a clinically relevant benefit over placebo in patient's global impression to be much or very much improved: 888 of 1710 (52%) on duloxetine and milnacipran (RD 0.19, 95% CI 0.12 to 0.26; NNTB 5, 95% CI 4 to 8) reported to be much or very much improved compared to 354 of 1208 (29%) of participants on placebo. Duloxetine and milnacipran had a clinically relevant benefit compared to placebo for pain relief of 30% or greater. RD was 0.10; 95% CI 0.08 to 0.12; NNTB 10, 95% CI 8 to 12. Duloxetine and milnacipran had no clinically relevant benefit for fatigue (SMD -0.13, 95% CI -0.18 to -0.08; NNTB 18, 95% CI 12 to 29), compared to placebo. There were no differences between either duloxetine or milnacipran and placebo in reducing sleep problems (SMD -0.07; 95 % CI -0.15 to 0.01). Duloxetine and milnacipran had no clinically relevant benefit compared to placebo in improving health-related quality of life (SMD -0.20, 95% CI -0.25 to -0.15; NNTB 11, 95% CI 8 to 14).There were 794 of 4166 (19%) participants on SNRIs who dropped out due to adverse events compared to 292 of 2863 (10%) of participants on placebo (RD 0.07, 95% CI 0.04 to 0.10; NNTH 14, 95% CI 10 to 25). There was no difference in serious adverse events between either duloxetine, milnacipran or desvenlafaxine and placebo (RD -0.00, 95% CI -0.01 to 0.00).There was no difference between desvenlafaxine and placebo in efficacy, tolerability and safety in one small trial.There was no difference between duloxetine and desvenlafaxine in efficacy, tolerability and safety in two trials with active comparators (L-carnitine, pregabalin). Authors' conclusions The update did not change the major findings of the previous review. Based on low- to very low-quality evidence, the SNRIs duloxetine and milnacipran provided no clinically relevant benefit over placebo in the frequency of pain relief of 50% or greater, but for patient's global impression to be much or very much improved and in the frequency of pain relief of 30% or greater there was a clinically relevant benefit. The SNRIs duloxetine and milnacipran provided no clinically relevant benefit over placebo in improving health-related quality of life and in reducing fatigue. Duloxetine and milnacipran did not significantly differ from placebo in reducing sleep problems. The dropout rates due to adverse events were higher for duloxetine and milnacipran than for placebo. On average, the potential benefits of duloxetine and milnacipran in fibromyalgia were outweighed by their potential harms. However, a minority of people with fibromyalgia might experience substantial symptom relief without clinically relevant adverse events with duloxetine or milnacipran.We did not find placebo-controlled studies with other SNRIs than desvenlafaxine, duloxetine and milnacipran.

/pdf/serotonin-and-noradrenaline-reuptake-inhibitors-snris-for-krtk0vjyua.pdf

Serotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia.

Background The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was planned for April 2017. Methods The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A systematic search of the literature from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Prospective population-based studies and systematic reviews with meta-analyses of case control studies were taken into consideration for the statements. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The statements were generated by multiple step formalized procedures. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. Results Current data do not enable identification of distinct factors in the etiology and pathophysiology of fibromyalgia syndrome. Fibromyalgia syndrome can be associated with inflammatory rheumatic diseases, gene polymorphisms, life style factors (e.g. smoking, obesity and lack of physical activity), depressive disorders as well as physical and sexual abuse in childhood and adulthood. Conclusion Fibromyalgia syndrome is most probably the end result of various pathogenetic factors and pathophysiological mechanisms.

[Etiology and pathophysiology of fibromyalgia syndrome : Updated guidelines 2017, overview of systematic review articles and overview of studies on small fiber neuropathy in FMS subgroups].

Hintergrund
Die planmasige Aktualisierung der S3-Leitlinie „Fibromyalgiesyndrom“, AWMF-Registernummer 145/004, war fur April 2017 geplant.

[Psychotherapy and psychological procedures for fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles].

The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A systematic search of the literature for systematic reviews of randomized, controlled studies on psychological and psychotherapeutic procedures from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was achieved by multiple step formalized procedures to reach a consensus. Efficacy, risks, patient preferences and applicability of available therapies were weighed up against each other. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. Cognitive behavioral therapies received a strong recommendation but biofeedback, guided imagery and hypnosis received a weak recommendation.

Psychotherapie und psychologische Verfahren beim Fibromyalgiesyndrom. Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten

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[Etiology and pathophysiology of fibromyalgia syndrome : Updated guidelines 2017, overview of systematic review articles and overview of studies on small fiber neuropathy in FMS subgroups].

[Psychotherapy and psychological procedures for fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles].

Psychotherapie und psychologische Verfahren beim Fibromyalgiesyndrom. Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten