[Role and place of ipidacrine in the therapy of diseases of the peripheral nervous system. The resolution of the expert council]. / Rol' i mesto ipidakrina v terapii zabolevanii perifericheskoi nervnoi sistemy. Rezolyutsiya Soveta ekspertov.

The resolution of the expert council is devoted to discussing aspects of the use of ipidacrine for the treatment of mononeuropathies, polyneuropathies and radiculopathies of various etiologies. Specialists prepared recommendations for ipidacrine's application in treating peripheral nervous system disorders.

[The role of food allergy as a provoking factor of migraine]. / Rol' pishchevoi allergii kak provotsiruyushchego faktora migreni.

OBJECTIVE: To assess the effect of food allergies on the course of migraine. MATERIAL AND METHODS: Seventy patients with migraine, aged 21-56 years old, were examined using headache diary, MIDAS and VAS, studies of specific antibodies of the IgG4 class (delayed type food allergy) by immuno-enzyme analysis (ELISA), microbiological examination of a smear from the mucous membrane of the posterior wall of the oropharynx with mass spectrometry of microbial markers (MSMM) with the identification of 57 microorganisms. RESULTS: We found an increase in specific IgG4 for a number of food allergens in most patients with migraine, of which 48.5% had a pronounced increase in IgG4 (>150 kEd/l) for at least one allergen (cow's milk - 13% patients, wheat flour - 5%, egg white - 47% or yolk - 26%, quail egg - 15%, sweet pepper - 6%), in 29% of people to several food allergens at once (all of them had chicken egg protein as one of the allergens). There was the association of IgG4 titers to wheat allergen with the severity of headache according to VAS (r-S=0.7; p=0.0046) in patients with the most severe, chronic migraine (17 people) and with an imbalance of the oropharyngeal microbiota, namely, concentration of pathological viruses Herpes spp. (rs=0.29; p=0.02), Epstein-Barr (rs=0.46; p=0.0002) and microscopic fungi (rs=0.39; p=0.0016), detected in these patients. CONCLUSION: We show for the first time the relationship between delayed-type food allergy and redistribution in the microbiome of the oropharynx of patients with migraine and once again confirm the role of delayed-type food allergy as a clinically significant factor influencing the course of migraine (its intensity and chronicity).

[The state of the oropharyngeal microbiome in patients with migraine]. / Sostoyanie mikrobioma rotoglotki u patsientov s migren'yu.

OBJECTIVE: To determine a role of changes in the oropharyngeal microbiome in the development and clinical manifestations of migraine. MATERIAL AND METHODS: Seventy patients with migraine, aged 21-56 years, and 15 healthy subjects matched for age and sex were examined using headache diary, MIDAS and VAS, the Gastrointestinal Symptom Rating Scale (GSRS), microbiological smear examination from the mucous membrane of the posterior wall of the oropharynx with evaluation by the method of mass spectrometry of microbial markers (MSMM) with determination of 57 microorganisms. RESULTS: The following changes in the oropharynx of individuals with migraine compared with the group of healthy individuals (control group) were found: a) a significant increase in the content of markers of resident (conditionally pathogenic) microorganisms characteristic of chronic diseases of the upper respiratory tract (strepto- and staphylococci); b) the appearance of markers of transient microorganisms normally absent, characteristic of the intestinal microflora (clostridia, gram-negative rods, enterobacteria, anaerobes); c) the appearance of viral markers of cytomegaloviruses, Herpes group, Epstein-Barr; d) a significant decrease in the content of bifidobacteria and lactobacilli). All people with migraine had a history or were found on examination to have chronic diseases of the upper respiratory tract (sinusitis in 48%, pharyngitis in 43%, tonsillitis in 25% of people), and gastrointestinal diseases. Dyspepsia was the most frequent and pronounced of the gastrointestinal syndromes on the GSRS in people with migraine (87%). This corresponds to the data on the extremely frequent occurrence of IBS (70% of patients) and other gastrointestinal pathology obtained from the patient history. CONCLUSION: In our work, the microbiota of the oropharynx in patients with migraine was studied for the first time using a new MSMM method. Disturbance of the oropharyngeal microbiome compared to the norm was detected in 100% of people with migraine. The changes characteristic of most patients included a significant decrease in the content of normal flora, an increase in the concentration of conditionally pathogenic microorganisms and the appearance of pathogenic microflora characteristic of chronic diseases of the upper respiratory tract and gastrointestinal tract, which may indicate their role in the pathogenesis of migraine.

[Comparative analysis of the use of symptomatic slow acting drugs for osteoarthritis containing chondroitin sulfate or affecting its biosynthesis in patients with non-specific low back pain]. / Sravnitel'nyi analiz primeneniya simptomaticheskikh preparatov zamedlennogo deistviya, soderzhashchikh khondroitina sul'fat ili vliyayushchikh na ego biosintez, u patsientov s nespetsificheskoi bol'yu poyasnichno-kresttsovoi lokalizatsii.

OBJECTIVE: Retrospective comparative analysis of the use of SYSADOA preparations containing chondroitin sulfate (Chondroguard, 2 ml, 25 amp., glycosaminoglycan-peptide complex, 1 ml 25 amp., bioactive concentrate of small marine fish, 2 ml, 10 amp.) in patients with chronic non-specific low back pain (LBP) of lumbar and sacral localization caused by spondylosis and osteochondrosis of the lumbar spine, at the stage of outpatient care. MATERIAL AND METHODS: Data of medical records of patients (n=120; men - 32, women - 88, age - 54.1±7.6 years, duration of disease exacerbation 4.0±1.7 months) with nonspecific LBP were systematized according to the inclusion/exclusion criteria. All patients were divided into 4 groups: Group 1 (n=30) received Chondroguard im., 2 ml every other day, the course of treatment was 25 injections, 25 days; Group 2 (n=30) received glycosaminoglycan-peptide complex on the 1st day - 0.3 ml, on the 2nd day - 0.5 ml, and then 3 times a week for 1 ml, course of treatment - 25 injections, 25 days; Group 3 (n=30) received bioactive concentrate of small marine fish, 2 ml im., every other day, the course of treatment was 10 injections; repeated courses of treatment - after 6 months; Group 4 (n=30) received Amelotex (meloxicam) at a dose of 15 mg once a day for 15 days. All patients of the first 3 groups received Amelotex at a dose of 15 mg with the possibility of reducing the dose to 7.5 mg or completely discontinuing the drug if necessary. Retrospectively, dynamic monitoring was performed in the medical records of outpatients after 50 days and 6 months from the start of therapy according to the following parameters: intensity of pain according to VAS, short form of the McGill pain questionnaire, vital signs of patients (Oswestry Disability Index, version 2.1a [Oswestry Disability Index], and Roland-Morris questionnaire), propensity to chronic pain syndrome according to the STarT Back Screening Tool questionnaire, the presence and severity of comorbid fibromyalgia according to the Fibromyalgia Rapid Screening Tool questionnaire, the level of pain catastrophization according to the Pain Catastrophizing Scale, the severity of comorbid anxiety and depression according to the Hospital Anxiety and Depression Scale, the severity comorbid insomnia (Insomnia Severity Index), quality of life according to the SF-36 scale, the effectiveness of drugs according to the patient on a 5-point scale, the need to take NSAIDs and analgesics, tolerability on a 4-point system. The safety of therapy was monitored using the WHO and Naranjo scales. RESULTS: In patients with nonspecific LBP, a greater degree of reduction in the intensity of the pain syndrome, a smaller number of exacerbations of the pain syndrome over 6 months of observation, an improvement in the functional status and life activity, a tendency to a decrease in the severity of anxiety and depression, sleep disturbances and comorbid fibromyalgia, limiting the risk of chronicity and catastrophization of pain, the presence of a structure-modifying effect on IVD and degenerative changes in the facet joints, a significant improvement in the physical and mental components of health, high satisfaction and safety of therapy, which included taking Chondroguard with meloxicam, with a decrease in the need to take the latter by the 50th day observation period compared to other regimens. The effects of Chondroguard and meloxicam turned out to be long-term and were recorded by the 6th month in the absence of Chondroguard, which indicated the preservation of the influence of highly purified cholesterol on the pathogenetic mechanisms of the formation of LBP. CONCLUSION: The study allows us to recommend the use of a parenteral form of cholesterol (Chondroguard, CJSC «PharmFirma «Sotex¼, Russia) for the treatment of nonspecific LBP with moderate or severe pain, chronic relapsing or persistent course, in combination with NSAIDs and their subsequent cancellation or administration on demand.

[Chronic fatigue syndrom: modern aspects of diagnosis and treatment]. / Sindrom khronicheskoi ustalosti: sovremennye aspekty diagnostiki i lecheniya.

The article presents a modern ecological approach to the pathogenesis and treatment of chronic fatigue syndrome (CFS). CFS is views in terms of gene-environment concept. The basic data in patients with CFS, triggers of diseases that implement the mechanisms responsible for the manifestation of symptoms are presented. A systematic approach to the diagnosis and treatment of diseases is given.

[The evaluation of the efficacy of Alflutop in the complex treatment of patients with chronic lower back pain (the observational study ZEITNOT)]. / Otsenka terapevticheskoi effektivnosti Alflutopa v kompleksnom lechenii patsientov s khronicheskoi bol'yu v nizhnei chasti spiny (nablyudatel'noe issledovanie TsEITNOT).

OBJECTIVE: To analyze the effect of Alflutop on neuroinflammation in patients with chronic lower back pain (CBP). MATERIAL AND METHODS: Forty-one patients with a verified CBP diagnosis were enrolled in the study. Alflutop was used for treating CBP, 1 ml once/day, for 20 days. Treatment efficacy was monitored using the Visual Analogue Scale (VAS), DN4 test; the Roland-Morris questionnaire; the index of pain activity in the lumbar spine; and the level of tumor necrosis factor-α (TNF-α) in blood plasma. There were three visits in total: screening (visit 0), treatment start (visit 1, 0-3 days after screening) and visit 2 (3 months later (±7 days) from the start of treatment). RESULTS: Before the start of therapy, in some patients (group 1, n=14 (34.1%) the TNF-α concentration in the blood plasma was below the detectable level (less than 4.0 pg/ml), while in group 2 (n=27 (659%)), the expression of TNF-α in peripheral blood was observed at the level of 6.3 [4.9; 7.4] pg/ml. Patients in group 2 significantly (p<0.05) differed from patients in group 1 by the greater number of CBP exacerbations over the last year as well as by the results of testing on DN4 (higher values) and SBI (greater discomfort). In group 2, a significant relationship was found between the TNF-α level in blood plasma and the number of exacerbations as well as between the TNF-α level and the number of DN4 points. At visit 2, patients in group 2 had a significant (p<0.05) decrease in pain intensity according to VAS, an improvement in the quality of life according to the Roland-Morris questionnaire, a decrease in the severity of the neuropathic component of pain according to DN4 test as well as subjective condition improvement associated with the activity of pain in the lumbar spine. A significant relationship was found between the level of TNF-α and the number of DN4 points after treatment and the period of active observation. CONCLUSIONS: In the majority of CBP patients, the high relapse rate and neuropathic nature of pain may be associated with persistent neuroinflammation due to TNF-α synthesis. Alflutop inhibits the TNF-α expression substantially, which significantly correlates with a decrease in the neuropathic pain syndrome component according to the DN4 questionnaire. The use of Alflutop can be considered as an effective method of treating patients with CBP, which has an impact on the process of neuroinflammation as one of the leading causes of changes in the pain nature and its chronicity.

[Clinical and psychological features in patients with incident and recurrent cases of benign paroxysmal positional vertigo]. / Kliniko-psikhologicheskie osobennosti patsientov pri vpervye voznikshikh i retsidiviruyushchikh pristupakh dobrokachestvennogo paroksizmal'nogo pozitsionnogo golovokruzheniya.

OBJECTIVE: To assess the clinical and psychological features in patients with incident and recurrent posterior canal BPPV. PATIENTS AND METHODS: The study included 47 patients (mean age 49.1±10.9 years; 12.8% of men and 87.2% of women) with idiopathic BPPV, posterior canal. According to the anamnesis, the patients were divided into two groups: 27 (57.4%) patients with incident BPPV (iBPPV) and 20 (42.6%) patients with recurrent BPPV (rBPPV). All patients were treated with repositioning Epley and/or Semont maneuvers until resolution of canalolithiasis. After that, clinical and psychological testing was immediately carried out, including short version of Vertigo Symptom Scale (VSS), Dizziness Handicap Inventory (DHI), Visual analogue scale (VAS) for fear of vertigo spells, Depersonalization-Derealization Inventory (DDI), Social Readjustment Rating Scale (SRRS) of Holmes and Rahe, Anxiety Sensitivity Index (ASI), Generalized Anxiety Disorder Scale (GAD-7) and Patient Health Questionnaire (PHQ). RESULTS: Patients with rBPPV compared with iBPPV had more severe symptoms of dizziness according to DHI (p=0.02) due to a functional and emotional subscales, as well as a more pronounced feeling of fear according to VAS (p=0.01). The data obtained on the remaining scales and questionnaires did not show statistically significant differences between the groups. The revealed results may indicate a greater predisposition of patients with rBPPV to the development of a special kind of mental disorders - functional dizziness or persistent postural-perceptual dizziness, which requires additional study and development of preventive measures.

[Multidomain approach in chronic non-specific back pain patient's treatment]. / Mul'tidomennyi podkhod k terapii patsientov s khronicheskoi nespetsificheskoi bol'yu v spine.

The concept of chronic nonspecific back pain (CNBP) as a pathology of the spine (osteochondrosis, spondylosis, intervertebral disc herniation, facet syndrome) is extremely outdated and has not justified itself, first of all, from the therapeutic view point. Numerous studies, including meta-analyzes and systematic reviews, have convincingly shown the ineffectiveness of the methods of CNBP treatment, aimed only at solving the problems of the spine itself and / or surrounding tissues. A substantial amount of special imaging studies have proven the dissociation between morphological vertebral changes and the clinical picture of pain. CNBP is the overall result of the interaction of numerous factors in the spine tissues (changes in the discs, joints, ligaments, fascia, muscles) and factors beyond the spine. The latter include, first of all, psychological and social factors, cognitive functions, the quality of night sleep, the level of physical activity, concomitant diseases (comorbidity). In each patient, the interaction of these factors determines the development of specific pathophysiological mechanisms of pain and, as a result, an individual clinical picture of pain (phenotype). Understanding these processes will allow for the reconsideration of the approach of searching for an anatomical pain source as the main pathogenetic factor; recognizing the multifocal generation of chronic pain as the result of a complex interaction of biological, psychological and social factors; the development of new principles and therapy algorithms. The authors propose to introduce into practice a multidomain screening approach for evaluating patients with CNBP, which would take into account the phenotype of pain, factors affecting its perception, and allow personalized treatment for each patient based on the biopsychosocial approach.

[Psychogenic pain]. / Psikhogennaia bol'.

Psychogenic pain is one of the urgent problems of medicine. To date, pathogenetic mechanisms of development of pain syndrome are unclear, there is no uniform classification. Pain, developing in patients with a mental disorder without an organic damage to the nervous system, and pain, which is a complication of an already existing pain syndrome of neuropathic or nociceptive nature, should be considered separately. Treatment of psychogenic pain syndromes should be integrated with the mandatory use of methods aimed at modifying the patient's lifestyle and attitude towards the illness.

[Ways of optimizing the management of patients with migraine in Russia (resolution of the council of experts)]. / Puti optimizatsii vedeniia patsientov s migren'iu v Rossii (rezoliutsiia soveta ékspertov).

Migraine is the third most common disease in the world. The overall prevalence of migraine in the Russian Federation is estimated at 20% with an estimated global prevalence of 14.7%. Migraine affects mostly people of working age and has a significant negative impact on the quality of life, the level of adaptation, ability to work, social functioning. Migraine represents a significant social and economic burden for patients and society as a whole. A team of national experts on migraine offers a program to prioritize quality of management of patients with headache.

[Melatonin in the treatment of low back pain and predictors of its efficacy]. / Melatonin pri boli v spine i prediktory ego éffektivnosti.

AIM: To assess analgesic properties of melatonin in the treatment of chronic non-specific low back pain and to study predictors of its efficacy. MATERIAL AND METHODS: A study included 178 patients, aged from 40 to 65 years, with chronic non-specific low back pain during >3 month and the VAS score >3. Patients were stratified into 6 groups (3 pairs of comparison). In the first pair, patients of both groups received a combination of 500 mg of glucosamine hydrochloride and 500 mg of chondroitin sulfate; in the second pair - a combination of 500 mg of glucosamine hydrochloride and 500 mg of chondroitin sulfate and diclofenac, in the third pair - diclofenac. All patients received additionally melaxen. The duration of the study was 3 month in the first pair and one month in the second and third pairs. With regard to response to melatonin, patients of the main groups were divided into responders and non-responders. Baseline factors determining the efficacy of treatment with melatonin were studied. RESULTS AND CONCLUSION: A significant reduction in pain intensity at movement and resting state was noted in all main groups compared to comparison groups. This result indicates possible analgesic properties of melatonin. Moreover, factors predicting the efficacy of such therapy were determined. Addition of melatonin to the standard scheme of low back pain treatment increases its efficacy, in particular in case of comorbidity of pain and sleep disorders and depressive symptoms.

[Headache immunology]. / Immunologiia golovnoi boli.

The overview is dedicated to the neuroimmunological mechanisms of headache development and chronification. Based on the analyzed data, the authors determined the relationship between immunological parameters and duration, intensity and other characteristics of this disease. These findings confirm that immunocompetent cells can be used as headache biomarkers and predictors of treatment efficacy. Questions about the role of separate parts of the immune system in the development and maintenance of a headache require further research. Studies of humoral immunity appeared to be very promising.

[An antinociceptive effect of chondroprotectors: a myth or a reality?].

Authors reviewed the literature on the efficacy of chondroprotectors in the treatment of chronic pain syndromes in comparison with placebo and other analgesics to discover the own antinociceptive effect of these drugs and mechanisms by which it occurs. Authors evaluated the results of various clinical studies on the effect of symptomatic slow-acting drugs for osteoarthritis (SYSADOA) on chronic pain syndrome in osteoarthritis and low back pain. We compared their effects with those of NSAIDs, celecoxib, or placebo. Assessment of pain and functional status was performed using WOMAC, VASandLeken's index as well as the Roland--Morrisquality of life questionnaire. The review of a number of clinical studies revealed a definite antinociceptive and anti-inflammatory effect of SYSADOA comparable with NSAIDs not only in the treatment of osteoarthritis, but also in chronic back pain, which is characterized by early onset and gradual development with a long-term retention of the result even after discontinuation of therapy. It has been shown that SYSADOA are able to reduce the level of inflammatory cytokines in the blood (IL-6, C-reactive protein) and to activate the production of anti-inflammatory cytokine IL-10 in the synovial membrane. It is shown that blocking of the effects of interleukin 1-beta and thereby inhibition of inflammatory enzymes like nitric oxide synthase and cyclooxygenase-2 is one of the points of glucosamine chondrocytes application. The data obtained in numerous studies that confirm the ability of SYSADOA to inhibit proinflammatory cytokines open the new perspectives for their use in the treatment of not only joint pain but also other chronic pain syndromes.

[A role of melatonin in the treatment of low back pain].

OBJECTIVE: To study an analgesic role of melatonin in the treatment of low back pain. MATERIAL AND METHODS: A study included 178 patients, aged from 40 to 65 years, with low back pain during at least 12 weeks and the VAS score > 3. Patients were stratified into 6 groups (3 pairs of comparison). In the first pair, patients of the main group (n = 31) received APTPA (a combination of 500 mg of glucosamine hydrochloride and 500 mg of chondroitin sulfate) in dosage 1 tablet twice a day during 1 month and then 1 tablet during 2 months plus melaxen (3 mg of melatonin 30-40 min before sleep), patients of the control group (n = 29) received only APTPA. In the second pair, patients of the comparison group (n = 30) received APTPA in dosage 1 tablet twice a day and diclofenac in dosage 25 mg 2-3 times a day, patients of the main group (n = 30) received additionally melaxen (3 mg of melatonin 30-40 min before sleep). In the third pair, patients of the main group (n = 29) received APTPA in dosage 1 tablet twice a day, diclofenac in dosage 25 mg 2-3 times a day and melaxen (3 mg of melatonin 30-40 min before sleep), patients of the comparison group (n = 29) did not receive melaxen. Treatment results were assessed after 3 months for the first pair and after 1 month for the second and third pairs. RESULTS: A significant reduction in pain intensity at movement and resting state was noted in the main groups compared to controls. CONCLUSION: Possible mechanisms of analgesic properties of melatonin and world experience in chronic low back pain treatment are discussed.

[Melatonin in chronic pain syndromes]. / Melatonin pri khronicheskikh bolevykh sindromakh.

Melatonin, a neurohormone synthesized by the epiphysis and extrapineal structures, has several functions including chronobiotic, antioxidant, oncostatic, immunomodulating, normothymic and anxiolytic ones. It impacts on the cardiovascular system and the gastrointestinal tract and is involved in reproductive functions, metabolism and body mass regulation. Moreover, recent studies have demonstrated the efficacy of melatonin in pain syndromes. The authors present a literature review on the studies of melatonin in treatment of fibromyalgia, headache, irritated bowel syndrome, chronic back pain and rheumatoid arthritis. Possible mechanisms of analgesic properties of melatonin are discussed. On one hand, there is the improvement of sleep and activation of own adaptive potential of melatonin by normalizing circadian rhythms inevitably disturbed in chronic pain syndromes. On the other hand, there are the data on the analgesic effect of melatonin realized through melatonin receptors and several neurotransmitter systems.

[Melatonin and pain].

OBJECTIVE: To study analgesic possibilities of melatonin. MATERIAL AND METHODS: A study included 120 patients, aged from 40 to 65 years, with low back pain. Duration of illness was not less than 12 weeks, the VAS score was >3. Patients were stratified into 4 groups (2 pairs of comparison). In the first pair, patients of the main group (n=31) received a chondroprotector АРТРА with the addition of melaxen (melatonin in dose 3 mg) and patients of the control group (n=29) received only АРТРА. In the second pair, patients of the control group (n=30) were treated with АРТРА and diclofenac and patients of the main group (n=30) received additionally melaxen. Treatment efficacy was assessed after 3 months for the first pair and after 1 month for the second pair. RESULTS: A significant reduction in pain intensity at both resting state and movement was noted in main groups compared to controls. CONCLUSION: Due to its therapeutic efficacy and good tolerability, melatonin may be regarded as a drug of choice in the complex treatment of chronic pain syndromes. Possible analgesic properties of melatonin and their mechanisms are discussed.

[Effect of maladaptive sets on the clinical picture and prediction of chronic headache of tension].

Forty women with chronic headache of tension (CHAT) and 20 women of comparison group with episodic headache of tension (EHAT) were studied. The clinical study included neurological examination with assessment of headache characteristics; psychometric examination - measurement of maladaptive psychological sets with the Pain Sets and Perceptions Inventory (PBPI) and assessment of pain catastrophization using a special scale. Higher scores of maladaptive sets on "mystery" and "stability" PBPI subscales (p<0,05) and on the Pain Catastrophization Scale (p<0,05) were seen in the CHAT group compared to the EHAT. After 2-month treatment with katadolon (300 mg/day), clinical characteristics of pain were significantly better (p<0,05) while maladaptive sets and pain catastrophization remained unchanged. Maladaptive sets are rigid cognitive formations and their high level in patients with CHAT may lead to relapse of primary symptoms some time after the effective treatment.