Douleur Neuropathique Research Articles

Perioperative Dexmedetomidine or Lidocaine Infusion for the Prevention of Chronic Postoperative and Neuropathic Pain After Gynecological Surgery: A Randomized, Placebo-Controlled, Double-Blind Study.

IntroductionThe transition of acute to chronic postoperative pain (CPP) remains a significant burden to the rehabilitation of patients. The research for adjuvants to prevent CPP continues; among others, dexmedetomidine and lidocaine seem promising agents.MethodsThis is a long-term follow-up of a randomized, placebo-controlled, double-blind study on women who underwent open abdominal gynecological surgery and received dexmedetomidine or lidocaine or placebo infusion perioperatively (n = 81). The effect of these adjuvants on the development of CPP and neuropathic pain was assessed during a 12-month follow-up. Eighty-one (81) women ASA I–II, aged between 30 and 70 years, were randomly assigned to receive either dexmedetomidine (DEX group) or lidocaine (LIDO group) or placebo (CONTROL group) perioperatively. Before anesthesia induction, all patients received a loading intravenous dose of either 0.6 μg/kg dexmedetomidine or 1.5 mg/kg lidocaine or placebo, followed by 0.6 μg/kg/h dexmedetomidine or 1.5 mg/kg/h lidocaine or placebo until last suture. Patients were followed up to obtain the long-term outcomes at 3, 6, and 12 months. At these time-points, pain intensity was assessed with the Numerical Rating Scale, (NRS: 0–10) and the development of neuropathic elements with the Douleur Neuropathique 4 (DN4) score. Prognostic parameters that could affect chronic pain and its components were also identified.ResultsData from 74 women were analyzed. Dexmedetomidine significantly reduced NRS scores comparing to placebo at 3 months (p = 0.018), while at 6 months, lidocaine was found superior to placebo (p = 0.02), but not to dexmedetomidine, in preventing neuropathic pain (DN4 < 4). Regarding secondary endpoints, higher NRS cough scores at 48 h were associated with statistically significant NRS and DN4 scores at 3, 6, and 12 months (p < 0.02). At 6 months, a statistically significant correlation was also found between higher NRS values and older age (p = 0.020).ConclusionsDexmedetomidine was superior to placebo regarding the duration and severity of CPP, while lidocaine exhibited a protective effect against neuropathic elements of CPP.Trial registrationClinicalTrials.gov identifier, NCT03363425.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-022-00361-5.

Capsaicin 8% Dermal Patch for Neuropathic Pain in a Pain Unit

AimsPain units manage approximately 20% of the patients with neuropathic pain, usually presenting with severe uncontrolled pain associated with substantial impairment of quality-of-life and disability. We aimed to analyze the experience with the capsaicin 8% dermal patch for managing patients with neuropathic pain in a pain unit. DesignThis was a post-authorization observational and retrospective study conducted at a single pain unit on patients with peripheral neuropathic pain under routine clinical care. MethodsDiagnosis of neuropathic pain was based on the Douleur Neuropathique 4 (DN4) questionnaire. Evaluations included pain intensity according to a visual analog scale and the quality-of-life as evaluated with the European Quality of Life-5 Dimensions (EQ-5D). ResultsWe included 66 patients with neuropathic pain lasting for a median of 24 months. The most frequent diagnosis was iatrogenic neuropathic pain (47%) and two thirds of patients exhibited extreme pain or discomfort. Pain intensity was reduced significantly from a mean (standard deviation [SD]) of 7.20 (1.95) at baseline to 6.02 (2.77) at month 3, leading to a mean change from baseline of 1.19 (95% confidence interval [CI], 0.59 to 1.78; p < .001; Cohen's d 0.49). The extent of the pain area was also significantly reduced from a median (interquartile range [IQR]) of 169.5 cm2 (69.3-299.9) at baseline to 121.2 cm2 (35.4-183.9) at month 3 (p < .001). There was an improvement in most dimensions of quality-of-life, especially regarding “usual activities,” “pain/discomfort,” and “anxiety/depression.” Tolerability was consistent with the known profile. ConclusionsOur results suggest that the capsaicin 8% dermal patch is a useful and well-tolerated treatment option for managing peripheral neuropathic pain in pain units.

Clinical Experience of High Frequency and Low Frequency TENS in Treatment of Diabetic Neuropathic Pain in Russia.

Background: Transcutaneous electrical nerve stimulation (TENS) is presently one of the main methods of treatment for neuropathic pain in type II diabetes mellitus. The discussion about which TENS frequency is more effective in the treatment of neuropathic pain has been ongoing for many years. Despite this, the response of different aspects of neuropathic pain to various TENS modalities has not been sufficiently studied. Aim: To analyze changes in characteristics of neuropathic pain depending on the frequency of TENS. Materials and methods: Seventy-five Russian diabetic patients with painful distal axonal neuropathy were enrolled in the study. Patients were assigned to three groups: in the HF TENS group, 25 patients received standard drug therapy (Alpha-lipoic acid, Pentoxifylline, Vitamin B12, Gabapentin) + high-frequency TENS (HF); in the LF TENS group, 25 patients received standard drug therapy (Alpha-lipoic acid, Pentoxifylline, Vitamin B12, Gabapentin) + low-frequency TENS (LF); in the control group, 25 patients underwent just standard drug therapy (Alpha-lipoic acid, Pentoxifylline, Vitamin B12, Gabapentin). Pain intensity was calculated before and after treatment with visual analogue scale (VAS), McGill pain questionnaire (MPQ), Douleur Neuropathique 4 Questions (DN4) and Pain Drawing. Results: TENS increased the therapeutic effect of standard drug therapy, in the treatment of neuropathic pain, by 65.9% and prolonged its efficacy by 31% for up to 6 months after treatment. HF TENS had a more pronounced analgesic effect than LF TENS based on VAS (34.7%), sensory (57.6%) MPQ dimensions and DN4 (21%). Affective MPQ dimension with the use of LF TENS was lower than HF TENS by 34.7% immediately after treatment, by 47.3% after 2 months and by 34.8% after 6 months of the follow-up period. Conclusion: There are significant differences between HF and LF TENS based on pain assessment using various pain scales. This reflects the distinctive effects of different TENS modalities on different aspects of neuropathic pain.

Prevalence of Neuropathic Pain in Patients with Fracture of the Distal Extremity of the Radius Treated with Volar Locking Plate.

Objective To evaluate the prevalence of persistent pain in the postoperative period of fractures of the distal extremity of the radius, as well as to detect early signs of neuropathic pain to develop protocols for the prevention of chronic postoperative pain. Methods Prospective study, carried out with 56 patients who underwent open reduction and internal fixation of fractures of the distal extremity of the radius with a volar locking plate from March to September 2020. The patients were submitted to assessment of neuropathic pain and functional capacity through the Douleur Neuropathique 4 questionnaire (DN4) and Quick Disabilities of the Arm, Shoulder, and Hand (Quick-DASH) questionnaires. Qualitative variables were compared using the Mann-Whitney U test and their correlation was analyzed using the Spearman Correlation and Equality of Two Proportions tests. Results A total of 43 patients aged between 18 and 66 years old were included in the present study; 39.5% of the participants scored ≥ 4 on the DN4 questionnaire. In relation to Quick-DASH, the average was 38.6. There was no statistically significant difference between the gender of the patient and the DN4 value ( p = 0.921). There was also no statistical correlation between the quantitative variables DN4 and Quick-DASH ( p = 0.061). Conclusions The prevalence of neuropathic pain in analyzed postoperative patients was significant, and the presence of signs and symptoms of neuropathic pain was a positive predictive factor for pain persistence beyond 2 months in 100% of cases. Thus, with early diagnosis of the neuropathic component of pain, associated with the nociceptive component, adequate pain control can be achieved, preventing its chronicity, and ensuring better rehabilitation.

The Effect of a Stretch and Strength-Based Yoga Exercise Program on Patients with Neuropathic Pain due to Lumbar Disc Herniation.

Randomized controlled trial. To investigate the effect of a stretch and strengthbased yoga exercise program on neuropathic pain due to LDH. LDH with neuropathic pain influences treatment outcomes negatively. Most yoga poses include the parameters of spinal training and help reduce pain and disability in patients with low back injuries. We hypothesized that yoga positively affects both LDH and neuropathic pain by increasing mobilization, core muscle strength, and spinal and hamstring flexibility. In total, 48 patients with neuropathic pain due to LDH were randomly assigned to a control group and a yoga group. All patients underwent a patient education program. In addition, the selected yoga exercise was taught and performed to the yoga group for one hour twice weekly for 12 weeks. Neuropathic pain (Douleur Neuropathique 4 for diagnosis; Leeds Assessment of Neuropathic Symptoms and Signs for severity), low back pain (the short-form of McGill Pain Questionnaire), disability (Oswestry Disability Index), and function (modified Schober and passive knee extension test) were measured blind before and at the one-, three-, and six-month follow-ups. The patient global assessment was applied at the six-month followup. The intention-to-treat analysis was performed in this study. The intention-to-treat analysis showed a statistically significant difference in neuropathic pain, patient global assess ment, low back pain, disability, and function in favor of the yoga group at post-treatment. The between-group effect sizes were moderate at six-months follow-up. It was determined that the selected stretch and strength-based yoga exercise could be a promising treatment option for neuropathic pain due to LDH. 2.

Therapeutic Efficacy of Traditional Chinese Medicine Syndrome-Based Formulae to Neuropathic Pain Caused by Chemotherapy.

Objective:Chemotherapy-induced neuropathic pain (CINP) is a troublesome complication of anti-cancer treatment. The aim of this retrospective study was to investigate the effectiveness of classic Chinese herbal formulae (CHF) Huang Qi Gui Zhi Wu Wu Tang (HQGZWWT) and Dang Gui Si Ni Tang (DGSNT) in the treatment of CINP.Materials and Methods:Douleur Neuropathique 4 (DN4) and Functional Assessment of Cancer Therapy-General (FACT-G) questionnaires were rated at baseline and after 3-monthly CHF treatment.Results:By searching through our medical records of all the CIPN patients from 2018 to 2019, we identified and enrolled 37 patients with Deficiency-Cold syndrome in the study, for whom the treatment of neuropathic pain by regular pharmacotherapies had failed or intolerable. At the third month evaluation with the DN4 questionnaire, 13 patients had symptomatic remission, 15 patients remained stable, and 9 patients had no response to CHF. The 3-month mean DN4 score was significantly higher than that at the baseline (P < .001). After CHF treatment, significant differences in quality of life were noted in the physical, social, emotional, and functional well-being subscales, and in the total score, of the FACT-G (P < .001). No adverse events or instances of disease progression were observed.Conclusions:The results of our small study are the first in the literature to show the clinical effectiveness of CHF for CINP. Combination of HQGZWWT and DGSNT is well tolerated and may offer the possibility to ameliorate CINP more than conventional care can. It merits further investigation.

Report on 25 Notalgia paresthetica cases: Clinical features and treatments.

Notalgia paresthetica (NP) is a neuropathic condition that manifests as a chronic itch on the back. The aim of this retrospective study was to examine the characteristics of patients diagnosed with NP. A total of 25 female patients, aged 26-64 years (mean+-10.67 years; median 47.17 years), were studied to determine the spinal or peripheral origin of NP. On radiological examination, discopathy was observed in 24% of the patients, arthrosis in 32%, and degeneration in 56%. There was no significant relationship found between dermatological symptoms and magnetic resonance imaging posi-tivity (p=0.188). The patients' treatment programs were based on either physical therapy (44%), local injection (28%), exercise therapy (16%), or physical therapy and kinesiotherapy (12%). Subjective measures for pain were validated with an average visual analog scale (VAS), and the 'Douleur Neuropathique 4' (DN4) questionnaire was used to screen for neuropathic pain. The VAS score of the patients before treatment was 7, and after treatment was 2. The mean DN4 score was 7 before treatment and 2 after treatment. NP is a rare syndrome of unknown etiology. We aim in this study to analyse NP clinical properties and treatment.

Neuropathic pain in athletes: basics of diagnosis and monitoring of a hidden threat.

The aim was to increase awareness about neuropathic pain in athletes and the available diagnostic criteria and explore the relevance to athletes and sports. In the report of its consensus meeting of 2016, the International Olympic Committee (IOC) noted the critical need to raise the awareness about pain and its management amongst sports physicians. The adequate management of pain requires recognition of its type and pathophysiological mechanisms. This is paramount in applying the multi-modal management of pain as a symptom or approach it as a disease. In athletes, the assessment of pain in general, and of neuropathic pain in particular, is more complex due to the impact of physiological, psychological and motivational factors and specific pathophysiological mechanisms on the pain threshold and tolerance. Neuropathic pain is not uncommon to encounter in athletes although not always recognised. Examples of neuropathic pain as a disease include complex regional pain syndrome (CRPS), peripheral neuropathy and spinal cord injuries. The recognition and diagnosis of neuropathic pain could be facilitated by the application of screening tools such as DN4 (Douleur Neuropathique 4) and LANSS (Leeds Assessment of Neuropathic Symptoms and Signs). Sports injuries may lead to neuropathic pain through different pathologies and mechanisms. Thus, neuropathic pain could be a real threat to athletes’ career if not promptly recognised and treated. We therefore believe that early recognition and expert management are mandatory for the best outcome.

Presence of Night Pain, Neuropathic Pain, or Depressive Disorder Does Not Adversely Affect Outcomes After Total Knee Arthroplasty: A Prospective Cohort Study.

A considerable proportion of patients warranting total knee arthroplasty (TKA) have night pain, neuropathic pain, and/or depressive disorder, which may not be resolved by TKA. This prospective, longitudinal cohort study aimed to document the prevalence of night pain, neuropathic pain, and depressive disorder in patients with advanced knee osteoarthritis undergoing TKA and to determine whether the specific coexisting pain and/or disorder at the time of TKA adversely affected postoperative outcomes. In this study, 148 patients undergoing TKA were longitudinally evaluated. The presence of night pain, neuropathic pain (determined using Douleur Neuropathique 4 [DN4]) and depressive disorder (determined using the Patient Health Questionnaire-9 [PHQ-9]) was determined before and 6 weeks, 3 months and 1 year after TKA. In addition, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and EuroQol-5 Dimension (EQ-5D) scores were assessed before and 1 year after TKA. Potential associations of night pain, neuropathic pain, and/or depressive disorder with pre- and postoperative WOMAC and EQ-5D scores were examined in subgroup analyses. Preoperatively, 72% (n = 106) of patients reported night pain, and the prevalences of neuropathic pain and depressive disorder were 15% and 17%, respectively. Preoperatively, compared with patients without night pain, those with night pain had significantly poorer preoperative WOMAC scores, but no significant difference was seen between groups 1 year after TKA. Preoperatively, the WOMAC, EQ-5D, and EQ-5D health scores of patients with neuropathic pain were not significantly different from those of patients without neuropathic pain, and there was no difference in clinical outcome scores 1 year after TKA between these groups. Preoperatively, the patients with depressive disorder showed significantly poorer preoperative WOMAC, EQ-5D, and EQ-5D health scores than those without depressive disorder, but no significant differences in scores were observed 1 year after TKA between these groups. This study revealed a considerable prevalence of night pain, neuropathic pain, and depressive disorder in patients undergoing TKA and that patients with these specific conditions reported poorer functional and quality of life scores preoperatively. However, such adverse effects disappeared after TKA. Our study findings suggest that TKA can provide satisfactory outcomes for patients with these specific conditions.

Stimulant use for self-management of pain among safety-net patients with chronic non-cancer pain

Background Chronic pain affects one-fifth of US adults. Reductions in opioid prescribing have been associated with increased non-prescription opioid use and, chronologically, increased stimulant (methamphetamine and cocaine) use. While non-prescription opioid use is commonly attributed to pain self-management, the role of stimulants in managing pain is unclear. Methods We analyzed baseline data from a longitudinal study of patients with chronic non-cancer pain in an urban safety-net healthcare system who had been prescribed an opioid for ≥3 of the last 12 months, and had a history of non-prescription opioid, cocaine, or amphetamine use (N = 300). We estimated the prevalence and identified correlates of stimulant use to treat pain among a subgroup of patients who reported past-year stimulant use (N = 105). Data sources included computer-assisted questionnaire (demographics, substance use, pain), clinical exam and procedures (pain, pain tolerance), and chart abstraction (opioid prescriptions). We conducted bivariate analyses to assess associations between demographics, pain characteristics, non-opioid therapies, substance use, opioid prescriptions, and self-reported symptoms, with reporting using stimulants to treat pain. Demographic variables and those with significant bivariate associations were included in a multivariable logistic regression model. Results Fifty-two percent of participants with past-year stimulant use reported using stimulants in the past year to treat pain. Participants who used stimulants for pain reported slightly higher average pain in the past 3 months (median of 8 (IQR: 6–8) vs 7 (7–9) out of 10, p = 0.049). In the multivariable analysis, female gender (AOR= 3.20, 95% CI: 1.06–9.63, p = 0.039) and higher score on the Douleur Neuropathique 4 neuropathic pain questionnaire (AOR = 1.34, 95% CI: 1.05–1.70, p = 0.017) were associated with past-year stimulant use to treat pain. Conclusion Stimulants may be used for pain self-management, particularly for neuropathic pain and among women. Our findings suggest an underexplored motivation for stimulant use in an era of reduced access to prescribed opioids.

Effect of melatonin on paclitaxel-associated acute and chronic pain: a randomized, double-blind, placebo-controlled clinical trial

Background: Taxane-induced pain is a disabling condition. This trial was conducted to assess the effects of melatonin on preventing paclitaxel-associated acute and chronic pain or decreasing its severity in patients with breast cancer. Methods: This randomized, double-blind, placebo-controlled clinical trial was conducted on breast cancer women who received weekly paclitaxel (80 mg/m2) with or without trastuzumab after using doxorubicin + cyclophosphamide. The intervention group randomly received oral melatonin (10 mg/day) or placebo, which started from the first night of chemotherapy and continued through the planned 12 weeks of chemotherapy. The level of arthralgia-myalgia as acute pain was assessed every day in both groups using the Brief Pain Inventory (BPI). The Douleur Neuropathique 4 questionnaire (DN4) and National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 were used to measure chemotherapy-induced peripheral neuropathy as chronic pain. Results: Seventeen patients were enrolled in each group randomly. The incidence of neuropathy according to a DN4 score ≥ 4 was significantly lower in the melatonin group versus the placebo group at week 12 compared to baseline (5 vs 11, P-value= 0.039). In addition, the mean neuropathy severity was significantly lower in the melatonin group over time (β= -0.051, P-value= 0.01). However, there were no significant differences in the mean worst and least pain scores over the twelve cycles of treatment between arms (P-value= 0.633, 0.341 respectively). Conclusion: Co-administration of melatonin in women with breast cancer decreased the incidence of severe paclitaxel-associated neuropathy but melatonin was not effective against acute pain.

Characteristics and Risk Factors of Persistent Neuropathic Pain in Recovered COVID-19 Patients.

ObjectivesTo assess risk factors for persistent neuropathic pain in subjects recovered from COVID-19 and to study the serum level of neurofilament light chain (NFL) in those patients.DesignCase-control studySettingPersistent post COVID-19 painSubjects45 patients with post COVID-19 pain and another 45 age and sex-matched healthcare workers who recovered from COVID-19 without pain.MethodsThe included participants were subjected to medical history taking, screening for depressive disorders, comprehensive neurological examination, and pain evaluation using the Douleur Neuropathique en 4 questions (DN4). All patients who had a score at least 4/10 on DN4 were included. The serum NFL level was measured for both groups at the time of patients’ enrollment.ResultsThe frequency of depression, moderate and severe COVID-19 cases, disease duration and serum ferritin were significantly higher in the cases with post COVID-19 pain than controls. Binary logistic regression revealed that depression, azithromycin use, moderate and severe COVID-19 increased the odds of post COVID-19 pain by 4.462, 5.444, 4.901, & 6.276 times, respectively. Cases with post COVID-19 pain had significantly higher NFL (11.34 ± 9.7, 95%CI: 8.42 – 14.25) than control group (7.64 ± 5.40, 95%CI: 6.02–9.27), (P-value= 0.029). Patients with allodynia had significantly higher NFL (14.96 ± 12.41, 95%CI: 8.58—21.35) compared to those without (9.14 ± 6.99, 95%CI: 6.43—11.85) (P-value= 0.05).DiscussionDepression, azithromycin, moderate and severe COVID-19 are independent predictors of persistent post COVID-19 pain. Serum NFL may serve as a potential biomarker for persistent neuropathic pain after COVID-19.

Characteristics and influence on quality of life of new-onset pain in critical COVID-19 survivors.

BackgroundPain is a clinical feature of COVID‐19, however, data about persistent pain after hospital discharge, especially among ICU survivors is scarce. The aim of this study was to explore the incidence and characteristics of new‐onset pain and its impact on Health‐Related Quality of Life (HRQoL), and to quantify the presence of mood disorders in critically ill COVID‐19 survivors.MethodsThis is a preliminary report of PAIN‐COVID trial (NCT04394169) presenting a descriptive analysis in critically ill COVID‐19 survivors, following in person interview 1 month after hospital discharge. Pain was assessed using the Brief Pain Inventory, the Douleur Neuropathique 4 questionnaire and the Pain Catastrophizing Scale. HRQoL was evaluated with the EQ 5D/5L, and mood disorders with the Hospital Anxiety and Depression Scale (HADS).ResultsFrom 27 May to 19 July 2020, 203 patients were consecutively screened for eligibility, and 65 were included in this analysis. Of these, 50.8% patients reported new‐onset pain; 38.5% clinically significant pain (numerical rating score ≥3 for average pain intensity); 16.9% neuropathic pain; 4.6% pain catastrophizing thoughts, 44.6% pain in ≥2 body sites and 7.7% widespread pain. Patients with new‐onset pain had a worse EQ‐VAS and EQ index value (p < 0.001). Pain intensity was negatively correlated to both the former (Spearman ρ: −0.546, p < 0.001) and the latter (Spearman ρ: −0.387, p = 0.001). HADS anxiety and depression values equal or above eight were obtained in 10.8% and 7.7% of patients, respectively.ConclusionNew‐onset pain in critically ill COVID‐19 survivors is frequent, and it is associated with a lower HRQoL.Trial registration No.: NCT04394169. Registered 19 May 2020. https://clinicaltrials.gov/ct2/show/NCT04394169.SignificanceA substantial proportion of severe COVID‐19 survivors may develop clinically significant persistent pain, post‐intensive care syndrome and chronic ICU‐related pain. Given the number of infections worldwide and the unprecedented size of the population of critical illness survivors, providing information about the incidence of new‐onset pain, its characteristics, and its influence on the patients’ quality of life might help establish and improve pain management strategies.

Effectiveness of Empagliflozin With Vitamin D Supplementation in Peripheral Neuropathy in Type 2 Diabetic Patients.

Background: Neuropathy is the most prevalent broad-spectrum microvascular complication of diabetes. The present study aims to evaluate the effect of empagliflozin with vitamin D supplementation on diabetic peripheral neuropathy.Methods: A prospective, randomized, controlled study was conducted for six months including 150 type 2 diabetic patients, divided into three groups (n=50/group): Group 1, patients on oral hypoglycemic agents; Group 2, patients on empagliflozin and Group 3, patients on empagliflozin with vitamin D. Biochemical parameters were estimated for outcome measurements and patients’ neuropathic pain was analysed using Douleur Neuropathique 4 Questions, Neuropathic Pain Symptom Inventory and Ipswich Touch the toes test questionnaire. Data were analysed using a one-way analysis of variance.Results: Diabetic neuropathy in males was more prevalent (more than 50%) as compared to females in all three groups, with an average age of 50±6 years, along with a diabetic history of 15±4.5 years and a glycated hemoglobin A1C (HbA1C) level of >10%. The mean value of serum vitamin D level significantly increased by 64.7% (19±5 to 54±8 ng/mL; p<0.05). A remarkable decrease (by 17.4%) from baseline in the HbA1C level was observed after six months of treatment only in Group 3, whereas in other groups (1 and 2), there was a non-significant decrease in HbA1C levels when compared to baseline. Moreover, a significant improvement in neuropathic condition was seen only in Group 3.Conclusion: The results indicated that empagliflozin with vitamin D supplementation significantly controlled or reduced HbA1C and improved diabetic neuropathic symptoms in patients. It is suggested that this combination can be considered as the primary therapeutic approach for neuropathic complications in diabetic patients.

Association of Genetic Variant at Chromosome 12q23.1 With Neuropathic Pain Susceptibility

Neuropathic pain (NP) has important clinical and socioeconomic consequences for individuals and society. Increasing evidence indicates that genetic factors make a significant contribution to NP, but genome-wide association studies (GWASs) are scant in this field and could help to elucidate susceptibility to NP. To identify genetic variants associated with NP susceptibility. This genetic association study included a meta-analysis of GWASs of NP using 3 independent cohorts: ie, Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS); Generation Scotland: Scottish Family Health Study (GS:SFHS); and the United Kingdom Biobank (UKBB). Data analysis was conducted from April 2018 to December 2019. Individuals with NP (ie, case participants; those with pain of ≥3 months' duration and a Douleur Neuropathique en 4 Questions score ≥3) and individuals with no pain (ie, control participants) with or without diabetes from GoDARTS and GS:SFHS were identified using validated self-completed questionnaires. In the UKBB, self-reported prescribed medication and hospital records were used as a proxy to identify case participants (patients recorded as receiving specific anti-NP medicines) and control participants. GWAS was performed using linear mixed modeling. GWAS summary statistics were combined using fixed-effect meta-analysis. A total of 51 variants previously shown to be associated with NP were tested for replication. This study included a total of 4512 case participants (2662 [58.9%] women; mean [SD] age, 61.7 [10.8] years) and 428 489 control participants (227 817 [53.2%] women; mean [SD] age, 62.3 [11.5] years) in the meta-analysis of 3 cohorts with European descent. The study found a genome-wide significant locus at chromosome 12q23.1, which mapped to SLC25A3 (rs369920026; odds ratio [OR] for having NP, 1.68; 95% CI, 1.40-2.02; P = 1.30 × 10-8), and a suggestive variant at 13q14.2 near CAB39L (rs7992766; OR, 1.09; 95% CI, 1.05-1.14; P = 1.22 × 10-7). These mitochondrial phosphate carriers and calcium binding genes are expressed in brain and dorsal root ganglia. Colocalization analyses using expression quantitative loci data found that the suggestive variant was associated with expression of CAB39L in the brain cerebellum (P = 1.01 × 10-14). None of the previously reported variants were replicated. To our knowledge, this was the largest meta-analyses of GWAS to date. It found novel genetic variants associated with NP susceptibility. These findings provide new insights into the genetic architecture of NP and important information for further studies.

Questionnaires can reflect the severity of electrophysiological findings In diabetic patients

Objective: The aim of this study was to determine whether a relationship exists between pain questionnaires, diabetic peripheral neuropathy, and the severity of electrophysiological findings. Methods: Patients with diabetes mellitus (DM) whose clinical signs and symptoms were found to be consistent with diabetic neuropathy were included in the present study in Ankara City Hospital Neurology Department between June 2020-January 2021. It was designed as a prospective cross-sectional study. Demographic characteristics, type and duration of DM, the onset of neuropathic complaints, systemic diseases, and DM treatments were noted. Blood tests were performed on all patients. Participants were administered the Douleur Neuropathique 4 Questions (DN4), Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), and Numerical Rating Scale (NRS) questionnaires and an electrophysiological examination. Results: The study included 108 patients. A statistically significant correlation was found between the severity of electrophysiological findings and the age of patients, duration of diabetes, and treatment modality. Additionally, a statistically significant correlation was found between the severity of electrophysiological findings and blood urea nitrogen (BUN) levels and monocyte and platelet counts. According to the NRS, a significant relation was found between BUN values and the severity of pain experienced. The LANSS predicted the severity of electrophysiological findings at a significantly higher accuracy than other questionnaires. Conclusion: Questionnaires can detect diabetic neuropathy, which is mostly asymptomatic, before the onset of DM complications. The LANSS questionnaire reflects the electrophysiological findings severity.

Neuropathic pain in primary knee osteoarthritis patients: correlation with physical function, quality of life, disease severity, and serum beta nerve growth factor levels

BackgroundNeuropathic mechanisms are thought to play a role in knee osteoarthritis (KOA) pain. Neuropathic pain questionnaires can promote diagnosis of a neuropathic component. Thus, we aimed to assess the frequency of neuropathic pain in primary KOA patients (using clinical questionnaires) and to investigate its correlation with socio-demographic factors, physical function, quality of life, disease severity, and serum beta nerve growth factor (β-NGF) levels.ResultsSeventy primary KOA patients were included. Neuropathic pain was detected in 52.9% of patients based on Douleur Neuropathique en 4 Questions (DN4) questionnaire and in 38.6% of patients based on Leeds assessment neuropathic pain symptoms and signs questionnaire (LANSS). Serum β-NGF levels were significantly higher in KOA patients than controls (P<0.0001), and in KOA patients with neuropathic pain compared with patients with non-neuropathic pain. DN4 score was positively correlated with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and physical function, and it was also negatively correlated with Osteoarthritis knee hip quality of life questionnaire (OAKHQOL) pain scores (rs=0.459, P<0.001; rs= 0.258, P= 0.031; rs= 0.307, P= 0.010; rs = −0.337, P= 0.004, respectively), while LANSS scale was positively correlated with symptom duration, WOMAC stiffness, Lequesne pain, and Lequesne index (rs= 0.260, P= 0.020; rs= 0.343, P= 0.004; rs= 0.344, P= 0.004; rs= 0.322, P= 0.007) and negatively correlated with OAKHQOL physical, OAKHQOL mental health, OAKHQOL social support, and total OAKHQOL scores (rs= −0.258, P= 0.031;rs= −0.254, P= 0.034; rs= −0.283, P= 0.018; rs= −0.261, P= 0.029 respectively).ConclusionsNeuropathic pain symptoms are frequent in primary KOA patients. KOA patients with neuropathic pain have worse quality of life, extreme disability, and higher serum β-NGF levels. Nerve growth factor inhibitors could have a potential role for not only relieving pain in KOA patients but also improving functional disability and quality of life in these patients.

Neuropathic pain in knee osteoarthritis

BackgroundThis study aimed to investigate the relationship between the neuropathic pain in knee osteoarthritis with the body composition, anthropometric and postural features, physical function, and quality of life.MethodsPatients with primary knee osteoarthritis, 50–70 years of age, were included in the study and divided into Group 1 with neuropathic pain and Group 2 with no neuropathic pain according to Douleur Neuropathique-4. The groups were compared in terms of demographic, clinical, radiological, laboratory findings and anthropometric measurements, body composition, physical function tests, osteoarthritis severity, quality of life, and posturography.Results200 patients were included in the study. 98 (82.6% female) were in Group 1 and 102 (74.5% female) in Group 2. Age was higher in Group 1 compared to Group 2 [61 (50–70) and 57.5 (50–70), respectively, p = 0.03]. Symptom duration was also longer in Group 1 (5.21 ± 4.76 and 3.38 ± 3.58, p = 0.002). Body mass indices were 31.9 ± 5.6 and 30.1 ± 4.8 (p = 0.015). Kellgren–Lawrence class, Western Ontario and McMaster Osteoarthritis Index and Short Form-36 scores were more unfavorable in Group 1. Although fall risk was similar, stability and Fourier harmony indices were impaired in Group 1 compared to Group 2 especially when the visual and proprioceptive input was blocked.ConclusionsAlmost half of the patients with knee osteoarthritis had neuropathic pain which was associated with longer symptom duration and higher age, lower education, higher body mass index, more severe radilogical findings, worse pain perception, lower physical function and quality of life, and lower stability.

There Is Association between Type of Pain and Hematologic Disorders

Background: Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage according to the International Association for the Study of Pain.Aim: To estimate distinguishing features of the pain in patients with blood disorders.Patients and Methods: The prospective exploratory study was conducted in the National Research Center for Hematology, Moscow from 11/2015 to 01/2021. In total, 40 patients (pts) with blood disorders who had a difficult-to-control pain syndrome were included in the study. There were 21 men (median age of 41.5, IQR 35.0-56.3 years) and 19 women (median age of 40, IQR 34.3-56.0 years). The pain types were determined according to clinical symptoms and the use of special questionnaires (i.e., the Douleur Neuropathique 4 Questions questionnaire for neuropathic pain). Pressure algometry was used to assess pain tolerance of the non-dominant hand by evaluating the pressure pain threshold (PPT, kg/cm 2), which is the minimum pressure required to induce pain.Results: Four types of pain were identified: neuropathic in 9 pts (22.5%), nociceptive in 9 pts (22.5%), their mix (summing up to a half of the total number of cases ‒ 52.5%, 21 pts) and dysfunctional pain in only 1 patient (2.5%). The distribution based on the pain types was uneven (Kolmogorov test, p = 0.05). The different pain types were related with various distributions of blood disorders: lymphoid tumor (44.5%), myeloid tumor (33.3%) and not tumor (22.2%) (associated with neuropathic pain) and myeloid tumor (88.9%) and not tumor (11.1%) (associated with nociceptive pain) (Figs. 1 and 2) . The tolerance of neuropathic and nociceptive pain types turned out to be significantly different (PPT medians with 95% CI): 2.2 kg/cm 2 (1.6-3.1) vs. 4.6 kg/cm 2 (3.9-5.5), respectively, and (found in ROC-analysis) the cut-off was 3.2 kg/cm 2,AUC (the area under ROC curve) 96.3%, sensitivity and specificity 88.8% (Fig. 3 and 4). PPT cut-off points, that shares the mixed pain (median 2.7 kg/cm 2, 95 CI 1.9-3.6) on the neuropathic and nociceptive pain are: 3.2 kg/cm 2 (AUC 67.0%) and 3.8 kg/cm 2 (AUC 86.7%), respectively. Several measurements of PPT (with taking into account the cut-off) in patient, suffering from pain, can help identify with a high probability his type of pain, and accordingly (indirectly), his blood type disorder.Conclusions: Measuring PPT in a pts with blood disorders allows to identify the type of pain (neuropathic, nociceptive, or combined), which can serve as an additional source of information for accurate diagnosis and treatment. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Frequency Rhythmic Electrical Modulation System (FREMS) to alleviate painful diabetic peripheral neuropathy: A pilot, randomised controlled trial (The FREMSTOP study).

Frequency Rhythmic Electrical Modulated System (FREMS) is a non-invasive treatment for chronic pain conditions, but its place in the treatment algorithm for painful diabetic peripheral neuropathy (PDPN) is unknown. A pilot, open-label, randomised controlled trial in individuals with PDPN inadequately controlled on at least dual neuropathic pain treatments recruited from primary and secondary care. Participants were randomised 1:1 to FREMS+usual care (n=13) versus usual care (n=12). Primary outcome was change from baseline in perceived pain (assessed by visual analogue scale) at 12weeks between treatment groups. Of 25 participants, 14 (56%) were men, and 21 (84%) were White Europeans. Median (IQR) age and duration of diabetes were 64 (56, 68) and 14 (10, 20) years, respectively. At 12weeks, FREMS showed improvements in perceived pain compared with baseline, although the change was not statistically significant from control group (-4.0[-5.0,0.4] vs. 0[-0.3,0.7], p=0.087). There were significant improvements in pain with FREMS, assessed by McGill Pain questionnaire (p=0.042) and Douleur neuropathique-4 questionnaire (p=0.042). More participants on FREMS had greater than 30 percent reductions in perceived pain compared with controls [7/13(54%) vs 0/12(0%), p=0.042] and significant improvements in Patient Global Impression of Change (p=0.005). FREMS intervention had moderate benefits in quality of life, sleep, depression and pain medication use, but these were not statistically significant. FREMS might be used to treat individuals with PDPN inadequately controlled on two classes of neuropathic pain medications and is associated with improvements in pain severity and perceived impact of treatment. A larger, appropriately designed trial assessing its impact in this population is needed.