Severity Of Neuropathic Pain Research Articles

Evaluation of (R)-[11C]PK11195 PET/MRI for Spinal Cord-Related Neuropathic Pain in Patients with Cervical Spinal Disorders

Activated microglia are involved in secondary injury after acute spinal cord injury (SCI) and in development of spinal cord-related neuropathic pain (NeP). The aim of the study was to assess expression of translocator protein 18 kDa (TSPO) as an indicator of microglial activation and to investigate visualization of the dynamics of activated microglia in the injured spinal cord using PET imaging with (R)-[11C]PK11195, a specific ligand for TSPO. In SCI chimeric animal models, TSPO was expressed mainly in activated microglia. Accumulation of (R)-[3H]PK11195 was confirmed in autoradiography and its dynamics in the injured spinal cord were visualized by (R)-[11C]PK11195 PET imaging in the acute phase after SCI. In clinical application of (R)-[11C]PK11195 PET/MRI of the cervical spinal cord in patients with NeP related to cervical disorders, uptake was found in cases up to 10 months after injury or surgery. No uptake could be visualized in the injured spinal cord in patients with chronic NeP at more than 1 year after injury or surgery, regardless of the degree of NeP. However, a positive correlation was found between standardized uptake value ratio and the severity of NeP, suggesting the potential of clinical application for objective evaluation of chronic NeP.

Persistent expression of NLRP3 in spinal microglia promotes development of lumbar disc degeneration.

Activated microglia play a critical role in the development of lumbar disc degeneration (LDD), which is a severe disease that causes neuropathic pain in affected people. Interleukin 1β (IL-1β) is a proinflammatory cytokine produced and secreted by activated microglia to induce the inflammation and the subsequent degradation of the disease discs. Recent findings suggest that activation of IL-1β in cells usually requires the involvement of NACHT, LRR and PYD domains-containing protein 3 (NLRP3)-induced formation of inflammasome. However, the importance of NLRP3 in spinal microglia in LDD is not known and thus addressed in the current study. NLRP3 expression was examined in the spinal discs. Correlation of NLRP3 levels in microglia with the pain score of the LDD patients or Thompson classification of the degeneration level of the patients was determined. The effects of persistent expression or depletion of NLRP3 on phagocytosis potential and production of proinflammatory cytokines in microglia were tested in vitro, while their effects on the severity of LDD and LDD-associated neuropathic pain were assessed in a mouse model for LDD. NLRP3 was exclusively expressed in microglia in the spinal discs. NLRP3 levels in microglia strongly correlated with the pain score of the LDD patients, and modestly correlated with the Thompson classification of the degeneration level of the patients. Persistent NLRP3 expression in microglia increased both their phagocytosis potential and production of proinflammatory cytokines, while NLRP3-depleted microglia decreased both their phagocytosis potential and production of proinflammatory cytokines. In a mouse model for LDD, persistent NLRP3 activation in microglia significantly increased the severity of LDD and LDD-associated neuropathic pain, while specific depletion of NLRP3 in microglia significantly attenuated the severity of LDD and reduced the LDD-associated neuropathic pain. Persistent activation of NLRP3 in spinal microglia promotes development of LDD, while suppression of NLRP3 in microglia could be a promising strategy for LDD therapy.

Multidimensional pain phenotypes after Traumatic Brain Injury.

More than 50% of individuals develop chronic pain following traumatic brain injury (TBI). Research suggests that a significant portion of post-TBI chronic pain conditions is neuropathic in nature, yet the relationship between neuropathic pain, psychological distress, and somatosensory function following TBI is not fully understood. This study evaluated neuropathic pain symptoms, psychological and somatosensory function, and psychosocial factors in individuals with TBI (TBI, N = 38). A two-step cluster analysis was used to identify phenotypes based on the Neuropathic Pain Symptom Inventory and Beck's Anxiety Inventory scores. Phenotypes were then compared on pain characteristics, psychological and somatosensory function, and psychosocial factors. Our analyses resulted in two different neuropathic pain phenotypes: (1) Moderate neuropathic pain severity and anxiety scores (MNP-AS, N = 11); and (2) mild or no neuropathic pain symptoms and anxiety scores (LNP-AS, N = 27). Furthermore, the MNP-AS group exhibited greater depression, PTSD, pain severity, and affective distress scores than the LNP-AS group. In addition, thermal somatosensory function (difference between thermal pain and perception thresholds) was significantly lower in the MNP-AS compared to the LNP-AS group. Our findings suggest that neuropathic pain symptoms are relatively common after TBI and are not only associated with greater psychosocial distress but also with abnormal function of central pain processing pathways.

QS63. Severity of Neuropathic Pain, Sensorimotor Impairments, and Sensory Neuron Abnormalities in Rat Model of Radiation Induced Neuropathy is Dose Dependent

Purpose: Radiation therapy (XRT) is one of the mainstays of cancer treatment, with approximately 50% of cancer patients requiring XRT as part of their treatment regimen. Of these patients, almost 31% subsequently suffer from debilitating neuropathic pain and sensory nerve abnormalities. XRT induced peripheral neuropathy results in progressive, intractable, and often irreversible nerve pain which can have a devastating effect on patients’ quality of life and potentially reduce the overall benefit of the therapy itself. We have previously established a novel rodent model of radiation induced peripheral neuropathy. The purpose of the present study was to assess neuropathic pain, sensorimotor impairments, and sensory neuron abnormalities in both clinically relevant and clinically high dose radiated animals. Methods: Eighteen male Lewis rats were randomly assigned to one of three experimental groups: (1) radiation of 35 Gray (Gy) divided into 5 daily doses of 7 Gy/day; (2) radiation of 70 Gray divided into 5 daily doses of 14 Gy/day, and (3) sham-radiated controls. All animals were tested at baseline in both pain and sensorimotor behavioral tests. Pain related measures included mechanical allodynia (von Frey test), cold allodynia (Acetone test), and thermal allodynia (Hargreaves test). Sensorimotor testing consisted of evaluation of overground locomotion using walkings tracks with calculation of the Sciatic Functional Index (SFI). Animals were tested serially over an 8 week period. At study endpoint, we performed nerve conduction analysis, electromyography (EMG), muscle force measurements, and all sciatic nerves were taken for histological/histomorphometrical analysis. In a separate cohort of animals, retrograde labeling was conducted in order to assess the level of sensory neuron death following radiation. Results: All animals that underwent radiation displayed significantly greater hypersensitivity to mechanical stimulation as compared to sham-radiated animals, indicative of chronic neuropathic pain. SFI values indicated sensorimotor impairments in radiated animals, and significantly lower twitch and tetanic muscle forces. Sensory neuron abnormalities and cell death were greater in radiated animals, with the high dose group displaying the most severe decrease. Conclusion: Results from this study demonstrate that neuropathic pain, sensorimotor behavioral impairment, and sensory neuron abnormalities vary as a function of radiation dose administered. Ongoing research is currently assessing novel therapeutic compounds to attenuate debilitating radiation induced sequelae, with the goal of improving the quality of life for cancer patients undergoing XRT.

RGMa Signal in Macrophages Induces Neutrophil-Related Astrocytopathy in NMO.

Repulsive guidance molecule-a (RGMa) is a glycosylphosphatidylinositol-linked glycoprotein which has multiple functions including axon growth inhibition and immune regulation. However, its role in the pathophysiology of neuromyelitis optica (NMO) is poorly understood. Perivascular astrocytopathy, which is induced by the leakage of aquaporin-4 (AQP4)-specific IgG into the central nervous system parenchyma, is a key feature of NMO pathology. We investigated the RGMa involvement in the pathology of NMO astrocytopathy, and tested a therapeutic potential of humanized anti-RGMa monoclonal antibody (RGMa-mAb). Using a clinically relevant NMO rat model, we evaluated the therapeutic effect of a RGMa-mAb by behavioral testing, immunohistochemistry, and gene expression assay. We further performed in vitro experiments to address the RGMa-signaling in macrophages. In both NMO rats and an NMO-autopsied sample, RGMa was expressed by the spared neurons and astrocytes, whereas its receptor neogenin was expressed by infiltrating macrophages. AQP4-IgG-induced astrocytopathy and clinical exacerbation in NMO rats were ameliorated by RGMa-mAb treatment. RGMa-mAb treatment significantly suppressed neutrophil infiltration, and decreased the expression of neutrophil chemoattractants. Interestingly, neogenin-expressing macrophages accumulated in the lesion expressed CXCL2, a strong neutrophil chemoattractant, and further analysis revealed that RGMa directly regulated CXCL2 expression in macrophages. Finally, we found that our NMO rats developed neuropathic pain, and RGMa-mAb treatment effectively ameliorated the severity of neuropathic pain. RGMa signaling in infiltrated macrophages is a critical driver of neutrophil-related astrocytopathy in NMO lesions, and RGMa-mAb may provide an efficient therapeutic strategy for NMO-associated neuropathic pain and motor deficits in patients with NMO. ANN NEUROL 2022;91:532-547.

Restless legs syndrome is associated with long-COVID in women.

Sleep disturbance is common in long-COVID (LC). Restless legs syndrome (RLS) is characterized by sleep disturbance and has been reported after viral infections. Therefore, we evaluated RLS symptoms cross-sectionally in individuals with LC at both current and pre-coronavirus disease 2019 (pre-COVID-19) time points. Adults on LC-focused Facebook pages were recruited for an online assessment of symptoms before COVID-19 infection and during their present LC state in a cross-sectional manner. The LC group documented baseline symptoms retrospectively. Questions were included about the presence/severity of RLS symptoms and assessments of fatigue, quality of life, and sleep apnea. A control group was recruited and included individuals ≥ 18 years of age who never had overt symptoms of COVID-19. Pregnancy was an exclusion criterion for both groups. There were 136 participants with LC (89.7% females, age 46.9 ± 12.9 years) and 136 controls (65.4% females, age 49.2 ± 15.5). RLS prevalence in females with LC was 5.7% pre-COVID-19 and 14.8% post-COVID-19 (P < .01) vs 6.7% in control females. Severity of RLS was moderate in both groups. Logistic regression predicting post-COVID-19 RLS among females with LC failed to find significant effects of hospitalization, sleep apnea, neuropathic pain severity, or use of antihistamines and antidepressants. The baseline prevalence of RLS in females with LC was similar to the general population group as well as to patients in epidemiological studies. The prevalence significantly increased in the LC state. Postinfectious immunological mechanisms may be at play in the production for RLS symptoms. Weinstock LB, Brook JB, Walters AS, Goris A, Afrin LB, Molderings GJ. Restless legs syndrome is associated with long-COVID in women. J Clin Sleep Med. 2022;18(5):1413-1418.

Postoperative pain after cardiac surgery: neurobiological basis and treatment

Despite the evolution of surgical techniques, pain continues to be one of the most frequent disorders in the postoperative period of cardiac surgery (CS), leading to the appearance of complications in the acute period and impairment of quality of life due to the appearance of chronic pain. In this narrative review, we aim to analyze the prognostic factors for the appearance of postoperative pain after CS, to locate and quantify the severity of neuropathic pain, and determine the most appropriate assessment methods in these patients. Postoperative pain in CS is a complex pain, which associates neuropathic, somatic and visceral components. Its origin is multifactorial; factors depending on the patient, the preoperative symptoms and the type of intervention, as well as sequelae derived from the surgery itself, determine the variability in its manifestation. Multiple studies have tried to identify the risk factors for its development, but the quantification of pain is limited by the subjective perception of the patients. Neurologists can play a relevant role in the differentiation of the different types of pain after CS, thanks to the understanding of its neurobiological bases, properly handling neuromodulators that control the neuropathic component of pain and collaborating in the indication of invasive techniques, necessary occasionally in the management of these patients.

Evaluation of Knowledge and Attitudes About The Traditional and Complementary Medicine Practices of the Patients with Neuropatic Pain Who Applied to the Physıcal Medicine and Rehabilitation Clinic

Objective: To evaluate the frequency of traditional and complementary medicine (TCM) use, the variety of applications, the sociodemographic and clinical characteristics of patients with neuropathic pain, and their knowledge and attitudes about TCM practices.Material and Methods: A total of 250 patients with neuropathic pain were included in this, cross-sectional study. The patients were divided into two groups: medication only (group 1, n=119) and medication with TCM practices (group 2, n=131). Questionnaires were completed by the patients in face-to-face interviews by a blinded physician.Results: The mean age of the patients in group 2 (50.68±16.39) was found to be higher than in group 1 (p=0.043). In terms of chronic diseases, hypertension, cardiovascular diseases, and other diseases were found to be more common in group 2 than in group 1 (p&amp;lt;0.05). The number of patients with duration of neuropathic pain more than 5 years, the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale and the Neuropathic Pain 4 (DN4) scale scores were found to be higher in group 2 than in group 1 (p&amp;lt;0.05). At least one TCM is known by %78.6 of group 2 and 61.3% of group 1 (p=0.003). The three most commonly used TCM practice in group 2 were wet cupping/cupping therapy (24%), leeches (22.8%), and acupuncture (11.6%).Conclusion: It was determined that the mean age of patients who used medication with TCM practices together for the treatment of neuropathic pain was higher, neuropathic pain severity was higher, and neuropathic pain duration was longer than patients who used medication only for the treatment of neuropathic pain.

Traumatic Spondyloptosis: Neurological, Surgical, and Outcome Perspectives in a Tertiary Care Center

Abstract Objective To evaluate traumatic spondyloptosis cases for neurological, surgical, and outcome perspectives. Materials and Methods This retrospective study includes 17 patients of spondyloptosis admitted in our department between August 2016 and January 2020. Each patient was evaluated in terms of demographic profile, clinical presentation, duration of injury, mode of injury, associated injuries, level and type of spondyloptosis, spinal cord status, nociceptive and neuropathic pain severity, severity of injury based on International Standards for Neurological Classification of Spinal Cord Injury (ISNCSI) assessment, surgical approaches, complications, and outcome. Unpaired t- test and Chi-square test were used for statistical analysis. Values with p &lt; 0.05 were considered statistically significant. Results Fall from height (58.8%) was the most common mode of injury. Most common level of spondyloptosis was T12–L1 (41.1%). Sagittal–plane spondyloptosis (76.5%) were more common than coronal–plane spondyloptosis (23.5%). Most common associated injury was musculoskeletal (64.7%). Neurological status of the patient at presentation (p = 0.0007) was significantly associated with outcome after 3 months of surgery/conservative management. Residual listhesis was present in 53.3% of patients postoperatively. Postoperative nociceptive pain (p = 0.0171) and neuropathic pain (0.0329) were significantly associated with residual listhesis. Duration of injury (p = 0.0228) was also significantly associated with postoperative residual listhesis. Conclusion Complete reduction of spondyloptosis should be the goal of surgery. Overall prognosis of spinal cord injury (SCI) due to traumatic spondyloptosis is poor.

Efficiency of 90-Min Extended EMLA-Induced Stimulated Skin-Wrinkling Test in the Diagnosis of Carpal Tunnel Syndrome.

Background:Previous researchers have used a 30-min eutectic mixture of local anesthetic (EMLA) test, which assesses the sympathetically mediated vasomotor function, in diagnosing carpal tunnel syndrome (CTS). However, its specificity was low, limiting its clinical diagnostic utility. In this study, we assessed the efficiency of 90-min extended EMLA-induced stimulated skin-wrinkling (SSW) test in CTS diagnosis.Methods:A cross-sectional study was designed among patients clinically diagnosed with CTS. Hands of healthy volunteers and the asymptomatic hands of selected patients served as control. The Boston symptom severity scale (SSS) and the neuropathic pain severity inventory (NPSI) were used to assess symptom severity, and nerve conduction study (NCS) was used to assess electrophysiological severity. EMLA-induced SSW was visually graded after 90 min of application and correlated with symptom and NCS severities.Results:Forty-two symptomatic hands and 30 asymptomatic hands were enrolled as cases and controls, respectively. The diagnostic efficiency of the extended EMLA test was found to be 83.4% for digit 2 and 87.3% for the lateral 4 digits (mean), whereas the diagnostic efficiency of standard NCS was 88.1%. Boston SSS and NPSI were better correlated with EMLA positivity than NCS positivity. A linear regression analysis showed negative correlation of wrinkling grade with NCS grade.Conclusion:With its improved diagnostic efficiency, the 90-min extended EMLA test can feasibly be used as an alternative to NCS, especially in general practice settings. Its potential clinical utility should be explored in a large population of CTS patients showing varying clinical and electrophysiological severities.

Identification of Neuropathic Pain Severity based on Linear and Non-Linear EEG Features.

The lack of an integral characterization of chronic neuropathic pain (NP) has led to pharmacotherapy mismanagement and has hindered advances in clinical trials. In this study, we attempted to identify chronic NP by fusing psychometric (based on the Brief Inventory of Pain - BIP), and both linear and non-linear electroencephalographic (EEG) features. For this purpose, 35 chronic NP patients were recruited voluntarily. All the volunteers answered the BIP; and additionally, 22 EEG channels positioned in accordance with the 10/20 international system were registered for 10 minutes at resting state: 5 minutes with eyes open and 5 minutes with eyes closed. EEG Signals were sampled at 250 Hz within a bandwidth between 0.1 and 100 Hz. As linear features, absolute band power was obtained per clinical frequency band: delta (0.1~4 Hz), theta (4~8 Hz), alpha (8~12 Hz), beta (12~30 Hz) and gamma (30~100 Hz); considering five regions: prefrontal, frontal, central, parietal and occipital. As non-linear features, approximate entropy was calculated per channel and per clinical frequency band with addition of the broadband (0.1~100 Hz). Resulting feature vectors were grouped in line with the BIP outcome. Three groups were considered: low, moderate, and high pain. Finally, BIP-EEG patterns were classified in those three classes, achieving 96% accuracy. This result improves a previous work of a SVM classifier that used exclusively linear EEG features and showed an accuracy between 87% and 90% per class to predict central NP after spinal cord injury.

MiR-338-5p Levels and Cigarette Smoking are Associated With Neuropathic Pain Severity in Individuals With Spinal Cord Injury: Preliminary Findings From a Genome-Wide microRNA Expression Profiling Screen

ObjectiveTo identify microRNA biomarkers and clinical factors associated with neuropathic pain after spinal cord injury. DesignCross-sectional, secondary analysis of baseline data collected from ongoing clinical studies. Using a genome-wide microRNA screening approach, we studied differential microRNA expression in serum from 43 adults with spinal cord injury enrolled in ongoing clinical studies. Least squares regression was used to identify associations between microRNA expression, clinical factors, and neuropathic pain severity. SettingCommunity-dwelling individuals with spinal cord injury. ParticipantsParticipants (N=43) were at least 18 years old with spinal cord injury, with 28 reporting neuropathic pain and 15 reporting no neuropathic pain. InterventionsNot applicable. Main Outcome MeasuresPain presence, type, and intensity were assessed with the International Spinal Cord Injury Pain Basic Data Set. Serum microRNA normalized deep sequencing counts were quantified from blood samples. Participant demographic factors, injury characteristics, medication use, and health habits were collected via questionnaire. ResultsmiR-338-5p expression and history of cigarette smoking were associated with and explained 37% of the variance in neuropathic pain severity (R2=0.37, F2,18=5.31, P=.02) independent of other clinical factors. No association was identified between miR-338-5p levels and nociceptive pain severity. ConclusionsOur findings suggest that miR-338-5p and cigarette smoking may both play a role in the development or maintenance of neuropathic pain after spinal cord injury. While additional work is needed to confirm these findings, validated target analysis suggests a neuroprotective role of miR-338-5p in modulating neuroinflammation and neuronal apoptosis and that its downregulation may result in maladaptive neuroplastic mechanisms contributing to neuropathic pain after spinal cord injury.

Evaluation and treatment of peripheral nervous system dysfunction in patients with prediabetes

The worldwide prevalence of prediabetes is steadily increasing, with up to a third of patients already showing signs of diabetic neuropathy (DN). Prediabetes includes impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or a combination of both.Recent diagnostic criteria of prediabetes according to Russian, European, and American clinical guidelines are presented. The review covers the most common forms of DN in patients with prediabetes (distal symmetric sensory polyneuropathy, painful DN, cardiovascular autonomic neuropathy) and their prevalence. Recommended methods of DN screening are discussed: diagnostic scales, sensory testing, nerve conduction study, autonomic testing, corneal confocal microscopy. The results of studies evaluating instrumental methods for diagnosing peripheral nervous system (PNS) dysfunction in prediabetes are discussed. Management tactics in patients with prediabetes and PNS dysfunction should include non-pharmacological and pharmacological interventions. Combining a low-calorie diet and regular physical activity can delay the development of diabetes mellitus and reduce the severity of neuropathic pain. In patients with painful DN, the first-line therapy includes pregabalin, gabapentin, and duloxetine. Since there is no current data on the effect of hypoglycemic therapy on the risks of development and/or progression of DN in patients with prediabetes, antioxidants are considered pathogenetic therapy. Alpha-lipoic acid (Berlition®) in the management of patients with prediabetes is discussed.

Corneal nerve loss is related to the severity of painful diabetic neuropathy

Background and purposePreviously it has been shown that patients with painful diabetic neuropathy (PDN) have greater corneal nerve loss compared to patients with painless diabetic neuropathy. This study investigated if the severity of corneal nerve loss was related to the severity of PDN.MethodsParticipants with diabetic neuropathy (n = 118) and healthy controls (n = 38) underwent clinical and neurological evaluation, quantitative sensory testing, nerve conduction testing and corneal confocal microscopy and were categorized into those with no (n = 43), mild (n = 34) and moderate‐to‐severe (n = 41) neuropathic pain.ResultsCorneal nerve fibre density (p = 0.003), corneal nerve fibre length (p < 0.0001) and cold perception threshold (p < 0.0001) were lower and warm perception threshold was higher (p = 0.002) in patients with more severe pain, but there was no significant difference in the neuropathy disability score (p = 0.5), vibration perception threshold (p = 0.5), sural nerve conduction velocity (p = 0.3) and amplitude (p = 0.7), corneal nerve branch density (p = 0.06) and deep breathing heart rate variability (p = 0.08) between patients with differing severity of PDN. The visual analogue scale correlated significantly with corneal nerve fibre density (r = −0.3, p = 0.0002), corneal nerve branch density (r = −0.3, p = 0.001) and corneal nerve fibre length (r = −0.4, p < 0.0001). Receiver operating curve analysis showed that corneal nerve fibre density had an area under the curve of 0.78 with a sensitivity of 0.73 and specificity of 0.72 for the diagnosis of PDN.ConclusionsCorneal confocal microscopy reveals increasing corneal nerve fibre loss with increasing severity of neuropathic pain and a good diagnostic outcome for identifying patients with PDN.

Risk factors for depression and anxiety in painful and painless diabetic polyneuropathy: A multicentre observational cross-sectional study.

BackgroundDespite the high prevalence of depression and anxiety in chronic pain conditions, current knowledge concerning emotional distress among painful diabetic polyneuropathy (pDSPN) and other diabetes mellitus (DM) sufferers is limited.MethodsThis observational multicentre cohort study employed the Hospital Anxiety and Depression Scale, the Beck Depression Inventory II and the State‐Trait Anxiety Inventory to assess symptoms of depression and anxiety in several groups with diabetes, as well as in a control group. The study cohort included 347 pDSPN patients aged 63.4 years (median), 55.9% males; 311 pain‐free diabetic polyneuropathy (nDSPN) patients aged 63.7 years, 57.9% males; 50 diabetes mellitus (DM) patients without polyneuropathy aged 61.5 years, 44.0% males; and 71 healthy controls (HC) aged 63.0 years, 42.3% males. The roles played in emotional distress were explored in terms of the biological, the clinical (diabetes‐, neuropathy‐ and pain‐related), the socio‐economic and the cognitive factors (catastrophizing).ResultsThe study disclosed a significantly higher prevalence of the symptoms of depression and anxiety not only in pDSPN (46.7% and 60.7%, respectively), but also in patients with nDSPN (24.4% and 44.4%) and DM without polyneuropathy (22.0% and 30.0%) compared with HCs (7.0% and 14.1%, p < 0.001). Multiple regression analysis demonstrated the severity of pain and neuropathy, catastrophic thinking, type 2 DM, lower age and female sex as independent contributors to depression and anxiety.ConclusionsIn addition to the severity of neuropathic pain and its cognitive processing, the severity of diabetic polyneuropathy and demographic factors are key independent contributors to emotional distress in diabetic individuals.SignificanceIn large cohorts of well‐defined painless and painful diabetic polyneuropathy patients and diabetic subjects without polyneuropathy, we found a high prevalence of the symptoms of depression and anxiety, mainly in painful individuals. We have confirmed neuropathic pain, its severity and cognitive processing (pain catastrophizing) as dominant risk factors for depression and anxiety. Furthermore, some demographic factors (lower age, female sex), type 2 diabetes mellitus and severity of diabetic polyneuropathy were newly identified as important contributors to emotional distress independent of pain.

Особливості впливу препарату келтикан та поляризуючого світла на ознаки невропатичного болю в комбінованій терапії діабетичної полінейропатії

Актуальність. Діагностика та лікування діабетичної полінейропатії мають особливе значення для хворих на цукровий діабет, оскільки вона може призводити до тяжких наслідків. Метою дослідження було підвищення ефективності лікування невропатичного болю шляхом включення препарату келтикан та поляризуючого світла в комплексну терапію діабетичної полінейропатії. Матеріали та методи. Обстежено 99 хворих на цукровий діабет 2-го типу, ускладнений діабетичною полінейропатією. Пацієнти були розподілені на 3 групи: до контрольної групи увійшли 32 пацієнти, які отримували стандартне лікування, 32 хворі 2-ї групи додатково отримували келтикан по 1 капсулі тричі на добу впродовж місяця, а 35 хворим 3-ї групи додатково було призначено 12 лікувальних процедур поляризуючим світлом. Оцінку інтенсивності невропатичного болю проводили за допомогою модифікованого опитувальника DN4. Результати. Установлено позитивний клінічний ефект лікування в усіх групах після 12-денного курсу лікування, який зберігався впродовж 3 місяців у 2-й та 3-й групах, а через 6 місяців — лише в групі з додатковим призначенням келтикану. Висновки. Використання опитувальника DN4 із модифікованою шкалою оцінки показників невропатичного болю дозволяє оптимізувати діагностику даного ускладнення у хворих на цукровий діабет. Включення препарату келтикан та поляризуючого світла в стандартну комплексну терапію діабетичної полінейропатії підвищує клінічну ефективність лікування невропатичного болю.

Hepatocyte growth factor, colony-stimulating factor 1, CD40, and 11 other inflammation-related proteins are associated with pain in diabetic neuropathy: exploration and replication serum data from the Pain in Neuropathy Study.

One in 5 patients with diabetes suffers from chronic pain with neuropathic characteristics, but the pathophysiological mechanisms underlying the development of neuropathic pain in patients with diabetic distal symmetrical polyneuropathy (DSP) are poorly understood. Systemic low-grade inflammation has been implicated, but there is still a considerable knowledge gap concerning its scope and meaning in this context. The aim of the study was to establish the broad inflammatory signature of painful diabetic DSP in serum samples from the Pain in Neuropathy Study, an observational cross-sectional multicentre study in which participants underwent deep phenotyping. In the present two cohorts exploration-replication study (180 participants in each cohort), serum samples from Pain in Neuropathy Study participants were analyzed with the Olink INFLAMMATION panel (Olink Bioscience, Uppsala, Sweden) that enables the simultaneous measurement of 92 inflammation-related proteins (mainly cytokines, chemokines, and growth factors). In both the exploration and the replication cohort, we identified a high-inflammation subgroup where 14 inflammation-related proteins in particular were associated with more neuropathy and higher pain intensity. The top 3 proteins were hepatocyte growth factor, colony-stimulating factor 1, and CD40 in both cohorts. In the exploratory cohort, additional clinical data were available, showing an association of inflammation with insomnia and self-reported psychological distress. Hence, this cross-sectional exploration-replication study seems to confirm that low-grade systemic inflammation is related to the severity of neuropathy and neuropathic pain in a subgroup of patients with diabetic DSP. The pathophysiological relevance of these proteins for the development of neuropathic pain in patients with diabetic DSP must be explored in more depth in future studies.

Peripheral Neuropathy: Comparison of Symptoms and Severity Between Colorectal Cancer Survivors and Patients With Diabetes.

Peripheral neuropathy (PN) is a common symptom in colorectal cancer (CRC) survivors and patients with diabetes. However, the differences in PN symptoms between CRC survivors and patients with diabetes are not clear. The purpose of this study was to examine the differences in PN between CRC survivors and patients with diabetes. Secondary data were analyzed from two cross-sectional studies consisting of 81 CRC survivors and 86 patients with diabetes from two hospitals in northern and central Taiwan. Data were analyzed using descriptive statistics, analysis of covariance, and multiple logistic regression. Significant differences in severity and prevalence of PN and neuropathic pain between CRC survivors and patients with diabetes were found. Patients with diabetes had significantly more severe PN and sensory PN compared to CRC survivors. In addition, the prevalence of PN and neuropathic pain was significantly higher in CRC survivors compared to patients with diabetes after control of covariates.

The synergistic effect of vitamin D supplement and mindfulness training on pain severity, pain-related disability and neuropathy-specific quality of life dimensions in painful diabetic neuropathy: a randomized clinical trial with placebo-controlled.

This study aimed to examine the synergistic effect of Vitamin D (VD) Supplement and mindfulness on neuropathic pain severity, Pain-Related Disability and Neuropathy-Specific Quality of Life (QOL) dimensions in painful diabetic neuropathy. In this randomized controlled trial, 225 patients with painful diabetic neuropathy were randomly allocated to five groups: (1) mindfulness and placebo, (2) placebo, (3) mindfulness, (4) VD, and (5) mindfulness and VD. Mindfulness training includes twelve sessions, and VD patients received a daily four thousand IU oral dosage (four capsules) with 28,000IU vitamin D weekly for 12weeks. Laboratory analyses, Sun exposure time, Vitamin D intake, BMI and physical activity were measured in pre-test and post-test. Pain-Related Disability measured with The Pain Disability Index (PDI). For other outcome variables, Neuropathy, a Specific QOL questionnaire and Neuropathic pain severity scale were utilized. Data were analyzed using one-way repeated-measures analysis of variance (ANOVA), Scheffe Post-hoc test and paired sample t-test. In baseline, measures were not different among the groups. At the end-of-treatment, results showed improvement in all groups except the "placeboonly" group for outcome variables. There was no difference between VD and mindfulness groups (within and not combined with placebo)in posttest. However, "VD + mindfulness" has a greater improvement rather than VD and mindfulness groups (P < 0.05). Moreover, both protocols have no significant effects on FBS, BMI and energy intakes (P > 0.05). Combining VD and mindfulness can reduce pain severity and pain-related disability, so with these changes, patients experienceimprovein their quality of life.

Cohort study protocol to characterize the incidence and severity of neuropathic pain in patients with severe acute respiratory syndrome coronavirus 2 infection.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in patients experiencing symptoms that include neurological dysfunction. As many viral infections are associated with neuropathy, the aim of the study is to characterize the incidence and severity of neuropathic pain in patients with COVID-19. A cohort study will be conducted in adult (≥18 years) patients who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Washington University/Barnes-Jewish Hospital. Participants who are deceased, with incomplete test results, or who cannot be contacted will be excluded. Approximately 1320 participants will be recruited in a 1:2 ratio of those with a positive-to-negative SARS-CoV-2 test result. Each participant will be invited to complete a survey to assess their symptoms related to neuropathy, 30 to 90 days after their initial SARS-CoV-2 test. Survey responses, demographics, and clinical data from the electronic health record will be used for analysis. The primary outcome is the incidence of new symptoms of neuropathic pain. The self-reported DN4 and Neuropathic Pain Symptom Inventory questionnaires (Appendix 1, http://links.lww.com/PR9/A103) will be used for neuropathic pain screening and severity assessment, respectively. Exploratory analyses will be performed to investigate other potential clinical endpoints and trends. Similar to previous coronavirus infections, an increased incidence of new-onset neuropathic pain after COVID-19 disease is expected, along with an increase in the severity experienced by patients with COVID-19 with pre-existing chronic pain. Comprehensive understanding of how COVID-19 affects the nervous system can provide a better framework for managing pain in this disease.