Treatment of neurological complications in patients with type 2 diabetes mellitus at the stage of rehabilitation after COVID-19

Although the predominant clinical manifestation of COVID-19 is a respiratory disease, various neurological symptoms are increasingly being diagnosed, in particular, diabetic polyneuropathy is diagnosed in most patients with diabetes, affecting large and small nerve fibers. Drugs that are traditionally used for neuropathic pain (tricyclic antidepressants, gabapentinoids, etc.), despite their positive effect in eliminating the symptoms of polyneuropathy, often cause side effects and do not impact nerve regeneration. Over the last decade, a group of nucleotides has been used quite actively. Additional information on the effects of this group of drugs was accumulated and there is a gradual transformation, including their compositions. Thus, recently the attention of researchers has been devoted to the study of the effectiveness of the combination of uridine, choline, vitamins B1, B6, B12, and folic acid, which is characterized by a fairly high safety profile and regenerative potential. The review highlights the mechanisms of action and results of clinical use of this combination. Uridine monophosphate, B vitamins, folic acid are involved in metabolic processes, enhancing nerve regeneration. This contributes to the development of indirect (secondary) analgesic effect. In addition, the data of new studies indicate the ability of uridine monophosphate derivatives to impact purinergic P2Y receptors, which causes a direct analgesic and direct regenerative effect. Studies have demonstrated the clinical efficacy of this combination in the main types of peripheral neuropathic pain. The combination did not cause side effects and was well tolerated. There was a reduction or complete withdrawal of concomitant analgesics against the background of improving the quality of life of patients. The combination of uridine, choline, vitamin B1, vitamin B6, vitamin B12, and folic acid is a very effective addition to the standard therapy of peripheral neuropathic pain of various genesis and rehabilitation after COVID-19.

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In Vitro and In Vivo Effects of Flavonoids on Peripheral Neuropathic Pain

Molecules ◽

10.3390/molecules25051171 ◽

2020 ◽

Vol 25 (5) ◽

pp. 1171 ◽

Cited By ~ 7

Author(s):

Paramita Basu ◽

Arpita Basu

Keyword(s):

Neuropathic Pain ◽

Side Effects ◽

Nerve Injury ◽

Somatosensory System ◽

Present Review ◽

Common Symptom ◽

Murine Models ◽

Peripheral Neuropathic Pain

Neuropathic pain is a common symptom and is associated with an impaired quality of life. It is caused by the lesion or disease of the somatosensory system. Neuropathic pain syndromes can be subdivided into two categories: central and peripheral neuropathic pain. The present review highlights the peripheral neuropathic models, including spared nerve injury, spinal nerve ligation, partial sciatic nerve injury, diabetes-induced neuropathy, chemotherapy-induced neuropathy, chronic constriction injury, and related conditions. The drugs which are currently used to attenuate peripheral neuropathy, such as antidepressants, anticonvulsants, baclofen, and clonidine, are associated with adverse side effects. These negative side effects necessitate the investigation of alternative therapeutics for treating neuropathic pain conditions. Flavonoids have been reported to alleviate neuropathic pain in murine models. The present review elucidates that several flavonoids attenuate different peripheral neuropathic pain conditions at behavioral, electrophysiological, biochemical and molecular biological levels in different murine models. Therefore, the flavonoids hold future promise and can be effectively used in treating or mitigating peripheral neuropathic conditions. Thus, future studies should focus on the structure-activity relationships among different categories of flavonoids and develop therapeutic products that enhance their antineuropathic effects.

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Neurological complications of diabetes mellitus

Medical Council ◽

10.21518/2079-701x-2019-9-40-44 ◽

2019 ◽

pp. 40-44

Author(s):

O. V. Kotova ◽

E. S. Akarachkova ◽

A. A. Belyaev

Keyword(s):

Diabetes Mellitus ◽

Diabetic Retinopathy ◽

Cognitive Function ◽

Diabetic Polyneuropathy ◽

Well Being ◽

Neurological Complications ◽

Nerve Fibers ◽

Antioxidant Effect ◽

Metabolic Disturbances ◽

Effective Drugs

Diabetes mellitus (DM) seriously and negatively affects the physical, mental and social well-being of patients. Among the complications of DM, neurological complications associated with both central and peripheral nervous system lesions are of great importance to the patient’s health. These include reduced cognitive function and neuropathy. A decrease in cognitive function associated with DM is observed in both patients with DM 1 and 2 types. There is a connection between the presence of diabetic retinopathy at baseline and changes in cognitive function over time in patients with DM2. Initial diabetic retinopathy and the severity of retinopathy are associated with a decrease in all cognitive functions and a decrease in the rate of information processing. The pathogenesis of diabetic polyneuropathy (DPN) is determined by metabolic disturbances in nerve and epithelial cells, which occur due to hyperglycemia and lead to impaired function of microcirculatory vessels and peripheral nerve fibers. Pathogenetic treatment of DPN is based on modern ideas about the mechanisms of its occurrence and progression. In particular, preparations with antioxidant effect are used, among which the efficacy of alpha-lipoic (thioctic) acid (ALA) in DPN is well proven, and one of such preparations is Berlithion («Berlin-Chemie», Germany). Among other effective drugs used in the treatment of neurological complications of DM, dipyridamole (Curantyl) is used, as the drug affects microangiopathy associated with DM.

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Neuropathic pain: mechanisms of development, principles of diagnostics and treatment

Pain medicine ◽

10.31636/pmjua.v4i2.1 ◽

2019 ◽

Vol 4 (2) ◽

pp. 4-32

Author(s):

Dmytro Dmytriiev ◽

Pylyp Prudius ◽

Olesia Zaletskaya ◽

Yevhen Lisak ◽

Yurii Rudnitsky ◽

...

Keyword(s):

Nervous System ◽

Neuropathic Pain ◽

Pain Syndrome ◽

Diabetic Polyneuropathy ◽

Pain Mechanisms ◽

Peripheral Neuropathic Pain ◽

Pain Pathways ◽

Mechanisms Of Development ◽

Somatosensory Nervous System ◽

Cause Of Pain

Neuropathic pain is a pain caused by a disease or focal damage to the somatosensory nervous system. The prevalence of chronic pain with neuropathic features in different countries is estimated at 7–10 %. Damages to the nervous system can occur at the level of peripheral nerves, plexus and dorsal roots (peripheral neuropathic pain) or spinal cord and brain (central neuropathic pain). Neuropathic pain is based on pathological activation of pain pathways. Neuropathic pain occurs with diabetic polyneuropathy more often than with all polyneuropathies of another etiology. Hyperglycemia is the major cause of chronic diabetes mellitus and its progression. Since the cause of pain can rarely be cured, treatment is usually symptomatic. Neuropathic pain is generally poorly controlled by analgesics. NB management is started with conservative pharmacotherapy before applying invasive analgesia. Although there are many drugs that can be used in patients with DPN, monotherapy can not always stop pain syndrome. In addition, the patient may not tolerate the full therapeutic dose of the drug. All this dictates the need for combination therapy.

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DN4 QUESTIONNAIRE IN FAMILY PRACTICE FOR EVALUATION OF CLINICAL MANIFESTATIONS OF NEUROPATHIC PAIN IN TYPE 2 DIABETES PATIENTS TREATED BY LIGHT THERAPY

International Journal of Medicine and Medical Research ◽

10.11603/ijmmr.2413-6077.2018.1.8717 ◽

2018 ◽

Author(s):

N. R. Makarchuk

Keyword(s):

Type 2 Diabetes ◽

Neuropathic Pain ◽

Pain Treatment ◽

Clinical Manifestations ◽

Diabetic Polyneuropathy ◽

Light Therapy ◽

Neurological Complications ◽

Pharmacological Agents ◽

Complex Therapy

Background. Peripheral diabetic polyneuropathy (DPN) is one of the most frequent neurological complications of diabetes mellitus (DM). Despite the large number of pharmacological agents, its treatment is not sufficiently effective, which necessitates the search for new therapies.Objective. The aim of the study was to increase the effectiveness of treatment of neuropathic pain in the patients with diabetic polyneuropathy by incorporating procedures using polarizing polychromatic non-coherent light (Bioptron light therapy) into the complex therapy of this disease.Methods. We examined 67 patients with type 2 diabetes complicated with diabetic polyneuropathy. Patients were divided into two groups: group 1 consisted of 32 patients, who received standard treatment; group 2 comprised 35 patients, who additionally underwent 12 light therapy treatments by means of the Bioptron Physiotherapy Unit. The evaluation of neuropathic pain intensity was performed using a modified questionnaire DN4. Results. A positive clinical effect of treatment was evidenced in both groups in 12 days of treatment. In 3 months, the intensity of complaints was significantly lower (p<0.05) only in the group with additional use of polarizing light. In 6 months, the positive effect of the therapy was leveled in the patients of both groups.Conclusions. The use of the DN4 questionnaire with a modified scale for assessing the parameters of neuropathic pain can optimize its diagnosis. The light therapy procedures together with the standard complex therapy of diabetic polyneuropathy increase the clinical efficacy of neuropathic pain treatment and help to preserve the therapeutic effect within 3 months.

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Cutaneous Neuroimmune Interactions in Peripheral Neuropathic Pain States

Frontiers in Immunology ◽

10.3389/fimmu.2021.660203 ◽

2021 ◽

Vol 12 ◽

Author(s):

Daniel B. Lowy ◽

Preet G. S. Makker ◽

Gila Moalem-Taylor

Keyword(s):

Neuropathic Pain ◽

Immune Cells ◽

Sensory Nerve ◽

Diabetic Polyneuropathy ◽

Sensory Innervation ◽

Skin Infections ◽

Peripheral Neuropathic Pain ◽

Emerging Therapies ◽

Allergic Contact ◽

Peripheral Sensory

Bidirectional interplay between the peripheral immune and nervous systems plays a crucial role in maintaining homeostasis and responding to noxious stimuli. This crosstalk is facilitated by a variety of cytokines, inflammatory mediators and neuropeptides. Dysregulation of this delicate physiological balance is implicated in the pathological mechanisms of various skin disorders and peripheral neuropathies. The skin is a highly complex biological structure within which peripheral sensory nerve terminals and immune cells colocalise. Herein, we provide an overview of the sensory innervation of the skin and immune cells resident to the skin. We discuss modulation of cutaneous immune response by sensory neurons and their mediators (e.g., nociceptor-derived neuropeptides), and sensory neuron regulation by cutaneous immune cells (e.g., nociceptor sensitization by immune-derived mediators). In particular, we discuss recent findings concerning neuroimmune communication in skin infections, psoriasis, allergic contact dermatitis and atopic dermatitis. We then summarize evidence of neuroimmune mechanisms in the skin in the context of peripheral neuropathic pain states, including chemotherapy-induced peripheral neuropathy, diabetic polyneuropathy, post-herpetic neuralgia, HIV-induced neuropathy, as well as entrapment and traumatic neuropathies. Finally, we highlight the future promise of emerging therapies associated with skin neuroimmune crosstalk in neuropathic pain.

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Comparative analgesic efficacy of ultrasound-guided nerve blocks induced by three anesthetics with different duration of action in the treatment of resistant neuropathic pain in the lower extremities

Vojnosanitetski pregled ◽

10.2298/vsp160617100j ◽

2019 ◽

Vol 76 (3) ◽

pp. 313-320

Author(s):

Olivera Jovanikic ◽

Gordana Andjelic ◽

Milan Lepic ◽

Dusica Mirkovic ◽

Bojan Jovanovic ◽

...

Keyword(s):

Neuropathic Pain ◽

Side Effects ◽

Local Anesthetics ◽

Chloride Solution ◽

Onset Time ◽

Daily Basis ◽

Nerve Blocks ◽

Peripheral Neuropathic Pain ◽

Minimal Dose ◽

Long Acting

Background/Aim. The neuropathic pain (NP) treatment is a big medical and socioeconomical problem. The new sorts of the NP treatment was developed and are applied in case of a medical treatment failure. The aim of this work was to investigate the efficacy of the ultrasound-assisted treatment of the resistant and chronic peripheral neuropathic pain with the local anesthetic nerve blocks. Due to the inefficacy of conventional treatment, three local anesthetics (shortacting, medium-term and long-acting) were administered in a series of the same minimal dose on a daily basis. Complications, side effects, the execution time of procedure and the onset time of local anesthetic were also investigated. Methods. In this prospective, randomized and doubleblinded study, 108 patients (of which 53 were diagnosed with diabetes and 55 with radiculopathy) with the resistant and chronic peripheral neuropathic pain in the lower extremities were treated with a series of ultra-sound assisted peripheral nerve blocks. The conventional treatment was exhausted. The presence of this neuropathic pain was confirmed by, at least, one of the three scales ? the Leeds Assesment of Neuropathic Simptoms and Signs (LANSS) scale, the Dolour Neuropathic 4 questions (DN4) scale and the pain DETECT(PD-Q) scale. Other therapies were not applied. The nerve blocks were administered on a daily basis until the relief of pain (visual analogue scale ? VAS < 30), and after that, two additional nerve blocks were given. The three local anesthetics of the different duration of therapeutic effect were given at the same minimal dose: the schortacting (1% procaine-chloride solution), medium-term (1% lidocaine-chloride solution) and long-acting (0.25% levobupivacaine-chloride solution) local anesthetics were used. The therapeutic efficacy was measured with the percentage reduction in the pain intensity on the VAS scale before and after the therapy and one month after the treatment: > 50% ? excellent results; 31?49% ? good results; < 30% the therapy did not work. The side effects, complications, the execution duration of procedure, the onset time of numbness, the number of corrections of the needle direction were recorded as well. Results. For all three groups: nerve blocks took 5.4 ? 1.48 minutes to do (withouth difference among the groups), the onset of numbness occured, on average, within 3.75 ? 2.62 minutes (withouth differences among the groups), and the need for corrections of needle direction was minimal (1.03 ? 0.17 corrections). All the patients experienced a loss of pain sensation (VAS < 30); when a long-acting anesthetic was used, the number of required nerve blocks was significant (p < 0.001) smallest (4.33 ? 0.63 blocks), than in other two groups, and the percentage pain reduction was highest (73.13%) (p < 0.001). The pain relief lasted one month after the therapy without the application of any other therapy. Neither complications nor side effects were observed. Conclusion. The procedure dercibed is a safe, efficient and easy-to-perform and does not lead to any complications and side effects. The pain relief is achieved most effectively and rapidly with the longacting local anesthetics, and maintained even for one month without the introduction of any additional therapy.

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Placebo responses in patients with peripheral neuropathic pain

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2014.05.019 ◽

2014 ◽

Vol 5 (3) ◽

pp. 210-210 ◽

Cited By ~ 2

Author(s):

Karen Lund ◽

Dyveke T. Demant ◽

Lene Vase ◽

Søren H. Sindrup ◽

Troels S. Jensen ◽

...

Keyword(s):

Neuropathic Pain ◽

Side Effects ◽

Pain Relief ◽

Pain Intensity ◽

Positive Emotions ◽

Rating Scale ◽

Placebo Treatment ◽

Peripheral Neuropathic Pain ◽

Explanatory Variables ◽

Anxiety Depression

Abstract Background and aim Treatment responses during placebo periods in randomized clinical trials (RCTs) are quite often substantial and may impede a positive outcome of the trial. It would therefore be beneficial to gain more knowledge on factors contributing to large placebo responses in RCTs. The aim of the current study was to identify predictors of placebo responses in patients with peripheral neuropathic pain. Hypotheses We hypothesized that a high baseline pain intensity and variability will be predictive of large responses during placebo treatment. Furthermore, we hypothesized that expectation for pain relief, few prior treatments and side effects, low scores of pain catastrophizing, anxiety, depression and the personality trait neuroticism and high levels of positive emotions will be predictors of placebo responses. Methods This study is part of a randomized, double-blind, placebo-controlled, crossover study with the anticonvulsant oxcarbazepine. Pain intensity was registered at baseline and during treatment periods on a numerical rating scale (NRS, 0–10) along with expectation for pain relief (NRS), psychological measures (scores for anxiety, depression, catastrophizing, neuroticism, and positive emotions), prior treatments, and side effects. Results Multiple regression analysis with pain reduction during placebo treatment as the dependent variable and baseline pain, age, gender, and pain duration as explanatory variables was highly significant (R-squared = 0.53, p < 0.001), while other explanatory variables did not reach statistical significance. Further analyses will be carried out. Conclusions Age and gender were not significant predictors of placebo responses in this study. Further results will be presented at the congress. Acknowledgements This study is part of the Innovative Medicines Initiative project EUROPAIN, www.imi.europa.eu.

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