The limited role of serum neurofilament light chain in predicting pain severity of patients with diabetic polyneuropathy.

Pain is one of many complaints expressed by patients with diabetic polyneuropathy. However, no objective measure for pain severity has been available. Neurofilament light chains have been widely used for assessing axonal damage in the neuronal system. Hence, we sought to investigate whether neurofilament light chains can serve as a marker reflecting pain severity in diabetic polyneuropathy. We enrolled the patients with diabetic polyneuropathy. Serum concentrations of neurofilament light chain were then measured using a single-molecule array. Pain severity was evaluated using painDETECT and the Brief Pain Inventory. Moreover, laboratory results including, serum creatinine, HbA1c, and glomerular filtration rate. A correlation test was used to analyze each variable. A total of 42 patients were enrolled. Neurofilament light chain levels were unable to reflect current neuropathic pain severity. However, high levels of neurofilament light chain were a significant predictor of poor diabetes control (r = 0.41; p = 0.02) and kidney damage (r = 0.45; p = 0.01). Serum levels of neurofilament light chain could not reflect current pain severity but was strongly associated with kidney dysfunction and poor diabetes control. Other biomarkers that could predict pain severity need to be uncovered.

Reliability of PainDETECT for Evaluating Low Back Pain Caused by Cluneal Nerve Entrapment.

BACKGROUND: Superior/middle cluneal nerve entrapment (CN-E) is an elicitor of low back pain (LBP). The painDETECT questionnaire is used to characterize CN-E symptoms. METHODS: Nineteen consecutive patients with LBP caused by CN-E (superior CN-E = 7; middle CN-E = 12) participated in a Japanese language painDETECT questionnaire survey before surgery. A score of 12 or lower was recorded as 'neuropathic component unlikely', a score of 19 or higher as 'neuropathic pain likely', and scores between 13 and 18 as 'neuropathic pain possible'. LBP severity was recorded on a numerical rating scale, the Roland-Morris Disability Questionnaire, and the EuroQol-5 dimension-5 level. RESULTS: The mean painDETECT score was 11.8 and did not significantly differ between the superior CN-E and middle CN-E groups. We classified low back pain as unlikely to have a neuropathic component in 13 patients, as likely to have a neuropathic component in 2 patients, and as possibly neuropathic in 4 patients. There was no significant difference in the pain level of patients with scores of ≤12 and ≥13 on painDETECT. All patients reported trigger pain; the positive rate was high for electric shock pain, radiating pain, and pain attacks and low for a burning or tingling sensation, pain elicited by a light touch, and pain caused by cold or hot stimulation. CONCLUSION: The painDETECT questionnaire may not reliably identify LBP caused by superior/middle CN-E as neuropathic pain. A diagnosis of LBP due to CN-E must be made carefully because symptoms resemble nociceptive pain.

Correlation analysis between the early diagnosis and severity of neuropathic pain and the activation level of NLRP3 inflammasome: A retrospective study.

To investigate the correlation between neuropathic pain's early diagnosis, severity, and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome activation, we retrospectively evaluated 50 patients with neuropathic pain and 50 healthy individuals. Activation of the NLRP3 inflammasome was measured in blood samples, as well as pain levels and clinical markers. Neuropathic pain patients exhibited elevated NLRP3 inflammasome activation. Pain intensity positively correlated with activation. Correlation was also observed with inflammatory markers and pain-related biomarkers. NLRP3 inflammasome demonstrated high diagnostic sensitivity. In conclusion, NLRP3 inflammasome activation influences neuropathic pain initiation and progression. Measuring activation levels may serve as an early diagnostic indicator and severity gauge for neuropathic pain.

[Features of course of pain syndrome in patients with schwannomatosis]. / Osobennosti techeniya bolevogo sindroma u patsientov s shvannomatozami.

OBJECTIVE: To identify the characteristics of pain syndrome in patients with schwannomas depending on genetic predisposition. MATERIAL AND METHODS: The study included 46 patients with peripheral, spinal and intracranial schwannomas, corresponding to the schwannomatosis phenotype according to the 2022 clinical criteria. All patients underwent sequencing of the LZRT1, Nf2 and SMARCB1 and a copy number study in the NF2. RESULTS: The most severe widespread pain was observed in patients with pathogenic LZRT1 variants, while patients with mosaic variants may not even have local tumor-related pain. Patients with SMARCB1variants may have no pain or have localized pain that responds well to surgical treatment. CONCLUSION: Further studies of the molecular features of schwannomatosis and driver mutations in the pathogenesis of pain are necessary to improve the effectiveness of pain therapy in this group of patients. Schwannomatosis is a disease from the group of neurofibromatosis, manifested by the development of multiple schwannomas. Neuropathic pain is one of the main symptoms characteristic of peripheral schwannomas, however, the severity and prevalence of the pain syndrome does not always correlate with the location of the tumors. According to modern concepts, the key factors influencing the characteristics of the pain syndrome are the target gene and the type of pathogenic variant. The most severe widespread pain is observed in patients with pathogenic variants in the LZRT1 gene, while patients with mosaic variants may not even have local pain associated with tumors. Patients with variants in SMARCB1 may have no pain or localized pain that responds well to surgical treatment.

Systematic Review and Metanalysis of the Expression of Blood-Based and Cerebrospinal Fluid-Based Biomarkers Related to Inflammatory Mediators in Neuropathic Pain.

BACKGROUND: The understanding of neuropathic pain remains incomplete, highlighting the need for research on biomarkers for improved diagnosis and treatment. This review focuses on identifying potential biomarkers in blood and cerebrospinal fluid for neuropathic pain in different neuropathies. METHODS: Searches were performed in six databases: PubMed, Web of Science, Scopus, Cochrane Library, EMBASE, and CINAHL. Included were observational studies, namely cross-sectional, cohort, and case-control, that evaluated quantitative biomarkers in blood or cerebrospinal fluid. Data were qualitatively synthesized, and meta-analyses were conducted using R. The study is registered with PROSPERO under the ID CRD42022323769. RESULTS: The literature search resulted in 16 studies for qualitative and 12 for quantitative analysis, covering patients over 18 years of age with painful neuropathies. A total of 1403 subjects were analyzed, identifying no significant differences in levels of C-Reactive Protein (CRP), Interleukin-6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-alpha) between patients with and without pain. Despite the high inter-rater reliability and adequate bias assessment, the results suggest negligible differences in inflammatory biomarkers, with noted publication bias and heterogeneity among studies, indicating the need for further research. CONCLUSIONS: Our review underscores the complex nature of neuropathic pain and the challenges in identifying biomarkers, with no significant differences found in CRP, IL-6, and TNF-alpha levels between patients with and without pain. Despite methodological robustness, the results are limited by publication bias and heterogeneity. This emphasizes the need for further research to discover definitive biomarkers for improved diagnosis and personalized treatment of neuropathic pain.

Post-polio syndrome - somatosensory dysfunction and its relation to pain: a pilot study with quantitative sensory testing.

OBJECTIVE: To explore and characterize somatosensory dysfunction in patients with post-polio syndrome and chronic pain, by conducting examinations with Quantitative Sensory Testing. DESIGN: A cross-sectional, descriptive, pilot study conducted during 1 month. SUBJECTS/PATIENTS: Six patients with previously established post-polio syndrome and related chronic pain. METHODS: All subjects underwent a neurological examination including neuromuscular function, bedside sensory testing, a thorough pain anamnesis, and pain drawing. Screening for neuropathic pain was done with 2 questionnaires. A comprehensive Quantitative Sensory Testing battery was conducted with z-score transformation of obtained data, enabling comparison with published reference values and the creation of sensory profiles, as well as comparison between the study site (more polio affected extremity) and internal control site (less affected extremity) for each patient. RESULTS: Derived sensory profiles showed signs of increased prevalence of sensory aberrations compared with reference values, especially Mechanical Pain Thresholds, with significant deviation from reference data in 5 out of 6 patients. No obvious differences in sensory functions were seen between study sites and internal control sites. CONCLUSION: Post-polio syndrome may be correlated with a mechanical hyperalgesia/allodynia and might be correlated to a somatosensory dysfunction. With lack of evident side-to-side differences, the possibility of a generalized dysfunction in the somatosensory system might be considered.

[Diagnosing neuropathic orofacial pain in the general dental practice]. / Diagnosticeren van neuropathische orofaciale pijn in de algemene tandartspraktijk.

Dental pain is a common reason for patients to visit the dentist. This type of pain is usually easy to diagnose and treat. However, diagnosing and treating other forms of orofacial pain remains complicated. One of the most challenging types of orofacial pain to diagnose and treat is neuropathic orofacial pain: pain resulting from damage to nerve tissue. Recognizing this type of pain in a timely manner can prevent unnecessary invasive dental treatments and disappointment for patients who seek help for this type of pain. There are relatively simple tools for dentists to distinguish neuropathic pain from other types of orofacial pain. The treatment of neuropathic pain is primarily focused on symptom relief through medication.

Current trends in the medical treatment of neuropathic low back pain: a Swedish registry-based study of 1.7 million people.

BACKGROUND: Low back pain, a common problem worldwide, causes more global disability than any other condition and is associated with high costs to society. This observational registry-based study describes the current trends in the medical treatment of neuropathic low back pain in the Swedish region of Västra Götaland, which has a population of 1.7 million. The study aims to; (1) identify the prevalence of neuropathic low back pain within the study population; (2) to explore the patterns of medical treatment utilization, including the prevalence and distribution of opioids (OG) and analgesics specified for neuropathic low back pain (NG) and (3) to evaluate the long-term trends and changes in medical treatment practice for neuropathic low back pain over the study period. METHODS: This study includes a descriptive analysis of aggregated data extracted from the Swedish primary care registry VEGA and the pharmaceutical prescription registry Digitalis between the years 2017 and 2021. The data were stratified by year, age, gender, pharmaceutical code (ATC), and sub-diagnoses and presented as the prevalence of unique patients retrieving prescribed medication within six months before or after a registered diagnosis of neuropathic low back pain. The pharmaceutical codes were furthermore grouped into two groups depending on their mechanism of action; opioid group (OG) and neuropathic group (NG). RESULTS: In all four diagnosis groups, more patients used opioid analgesics than neuropathic analgesics. The greatest difference between the opioid group and neuropathic group was in the lumbar spinal stenosis diagnosis group (67.1% vs. 40.6%), followed by the lumbar root canal stenosis diagnosis (65.9% vs. 44.2%), the nerve root and plexus compressions in intervertebral disc disorders diagnosis (57.5% vs. 40.8%), and lumbago with sciatica diagnosis (38.4% vs. 22.7%). CONCLUSIONS: The trends suggest a general increase in the prescription rate and therefore patients' use of neuropathic analgesics for neuropathic pain associated with the studied diagnoses. However, opioid treatment remains the most common. The results indicate that the treatment for neuropathic low back pain needs to be improved.

Multidisciplinary strategies to treat painful mononeuropathies in the upper extremity: from lab to bedside.

Neuropathic pain in the upper extremity is a serious problem, commonly involving relatively young patients. The pain causes loss of function and productivity, changes a patient's lifestyle and can progress into a chronic pain syndrome with secondary psychosocial co-morbidities. Treating patients with a painful mononeuropathy remains challenging, with a monodisciplinary approach often having limited treatment efficacy. This narrative review discusses how to deal with this challenge in the treatment of patients with peripheral nerve injury pain, addressing the four important pillars: (1) diagnosing a painful mononeuropathy; (2) clinical pain phenotyping; (3) personalized pain treatment; and (4) using a multidisciplinary team approach.

Neuropathic pain in cats: Mechanisms and multimodal management.

PRACTICAL RELEVANCE: Chronic pain is a significant welfare concern in cats, and neuropathic pain, which arises from aberrant processing of sensory signals within the nervous system, is a subcategory of this type of pain. To comprehend this condition and how multimodal pharmacotherapy plays a central role in alleviating discomfort, it is crucial to delve into the anatomy of nociception and pain perception. In addition, there is an intricate interplay between emotional health and chronic pain in cats, and understanding and addressing the emotional factors that contribute to pain perception, and vice versa, is essential for comprehensive care.Clinical approach:Neuropathic pain is suspected if there is abnormal sensation in the area of the distribution of pain, together with a positive response to trial treatment with drugs effective for neuropathic pain. Ideally, this clinical suspicion would be supported by confirmation of a lesion at this neurolocalisation using diagnostic modalities such as MRI and neuroelectrophysiology. Alternatively, there may be a history of known trauma at that site. A variety of therapies, including analgesic, anti-inflammatory and adjuvant drugs, and neuromodulation (eg, TENS or acupuncture), can be employed to address different facets of pain pathways.Aim:This review article, aimed at primary care/ general practitioners, focuses on the identification and management of neuropathic pain in cats. Three case vignettes are included and a structured treatment algorithm is presented to guide veterinarians in tailoring interventions.Evidence base:The review draws on current literature, where available, along with the author's extensive experience and research.

Cranial Neuralgias.

OBJECTIVE: The cranial neuralgias are relatively rare, but recognizing these syndromes and distinguishing among them is critical to reducing unnecessary pain and disability for affected patients. Despite their distinctive features, cranial neuralgias may go undiagnosed or misdiagnosed for several years. A notable proportion of cranial neuralgia presentations are due to secondary causes and require targeted treatment. The purpose of this article is to review the diagnosis and management of cranial neuralgias encountered in clinical practice. LATEST DEVELOPMENTS: In 2020, the International Classification of Orofacial Pain was released for the first time. Modeled after the International Classification of Headache Disorders, it includes updated terminology for cranial neuralgias. The underlying pathophysiology of the cranial neuralgias is currently believed to be rooted in both peripheral and central nociceptive systems. In addition, a growing number of familial cases are being identified. Recent therapeutic advancements include a better understanding of how to utilize older therapies and procedures more effectively as well as the development of newer approaches. ESSENTIAL POINTS: Cranial neuralgia syndromes are rare but important to recognize due to their debilitating nature and greater likelihood of having potentially treatable underlying causes. While management options have remained somewhat limited, scientific inquiry is continually advancing the understanding of these syndromes and how best to address them.

Neuropathic and Nociplastic Pain Profiles are Common in Adult Chronic Nonbacterial Osteitis (CNO).

Chronic nonbacterial osteitis (CNO) is a rare musculoskeletal disease causing chronic bone pain. It is known that chronic musculoskeletal pain may involve other mechanisms than nociceptive pain only. We investigate the prevalence of neuropathic and nociplastic pain in adult CNO and their association with clinical characteristics and treatment outcomes. Survey study among the Dutch adult CNO cohort (n = 84/195 participated), including PAIN-detect for neuropathic pain, and the Central Sensitization Inventory (CSI), Fibromyalgia Rapid Screening Tool (FiRST), and ACTTION-APS Pain Taxonomy (AAPT) for nociplastic pain. Clinical characteristics and CNO-related bone pain scores were compared between patients with exclusive nociceptive pain and those with nociceptive pain plus neuropathic and/or nociplastic pain (mixed pain). 31% (95% CI 21-41) of patients classified as likely having neuropathic pain according to PAIN-detect. 53% (41-64) of patients displayed central sensitization on CSI, 61% (50-72) screened positive for fibromyalgia on FiRST and 14% (7-23) of patients fulfilled the AAPT criteria, all indicative of nociplastic pain. Mixed pain was associated with longer diagnostic delay (mean difference 2.8 years, 95% CI 0.4-5.2, p = 0.023), lower educational level (72% versus 20%, p < 0.001), and opioid use (37% versus 13%, p = 0.036). Despite comparable disease severity and extent, patients with mixed pain reported significantly higher CNO-related bone pain scores. This study demonstrates the high prevalence of mixed pain in adult CNO, in which neuropathic and nociplastic pain exist alongside nociceptive inflammatory bone pain. Disease burden in CNO may extend beyond inflammatory activity, highlighting the need for a multifaceted management approach.

An overview of diagnosis and assessment methods for neuropathic pain.

Neuropathic pain, defined as pain arising as a consequence of a lesion or disease affecting the somatosensory nervous system, requires precise diagnostic assessment. Different diagnostic tools have been devised for the diagnosis of neuropathic pain. This review offers insights into the diagnostic accuracy of screening questionnaires and different tests that investigate the somatosensory nervous system, in patients with suspected neuropathic pain. Thus, it illustrates how these tools can aid clinicians in accurately diagnosing neuropathic pain.

Pain type and neuropathic pain components in acute herpes zoster.

OBJECTIVES: The aim of this study was to investigate the pain type (nociceptive or neuropathic) and neuropathic pain components in patients with acute herpes zoster (HZ). METHODS: Patients with acute HZ referred to the outpatient Dermatology and Venereology clinic between January 2021 and January 2022 were retrospectively detected. The demographic data including gender and age, rash localization, pain severity, and neuropathic pain components were recorded. Pain severity and neuropathic pain components were evaluated using a Visual Analog Scale (VAS) and Douleur Neuropathique 4 (DN4), respectively. RESULTS: The study included a total of 58 patients, comprising 33 females and 25 males. Of these patients, 35 (60.3%) were found to have neuropathic pain. Itching, burning, pins and needles, and tingling were the most frequently reported neuropathic pain signs and symptoms. The proportion of female patients with neuropathic pain was found to be significantly higher than that of male patients (p=0.021). No significant differences were observed in the distribution of pain across different body sites or in the age of patients with neuropathic pain (p>0.05). Itching was significantly more common in younger patients (p=0.02). CONCLUSION: In conclusion, the study found that over half of the patients with acute HZ experienced neuropathic pain, and this was more frequently observed in female patients. Analysis of different components of neuropathic pain showed significant differences in age, gender, and site distribution. The findings of this study may have important implications for the manage-ment and treatment of acute HZ.

Age and Sex Differences in Pediatric Neuropathic Pain and Complex Regional Pain Syndrome: A Scoping Review.

BACKGROUND: Age and sex differences may exist in the frequency (incidence, prevalence) or symptoms of neuropathic pain (NP) and complex regional pain syndrome (CRPS) due to biopsychosocial factors (eg, neurodevelopment, physiological and hormonal changes, psychosocial differences) that evolve through childhood and adolescence. Age and sex differences may have implications for evaluating screening and diagnostic tools and treatment interventions. OBJECTIVE: To map the existing literature on pediatric NP and CRPS with respect to age and sex distributions, and age and sex differences in symptomology and frequency. METHODS: A scoping literature review was conducted. Databases were searched from inception to January 2023. Data were collected on study design, setting, demographics, and age and sex differences in frequency and symptoms. RESULTS: Eighty-seven studies were included. Distribution of participants with CRPS (n=37 studies) was predominantly early adolescence (10 to 14 y) and female sex, while NP (n=42 studies) was most commonly reported throughout adolescence (10 to 19 y) in both sexes. Forty-one studies examined age and sex differences in frequency; 6 studies reported higher frequency in adolescence. Very few studies (n=11) examined differences in symptomology. DISCUSSION: Large epidemiological studies are required to further understand age and sex differences in frequency of pediatric NP and CRPS. Age and sex differences must be considered when evaluating screening and diagnostic tools and treatment interventions to ensure relevance and validity to both sexes and across ages. Validated tools will improve understanding of age-dependent and sex-dependent differences in symptoms, pathophysiology, and psychosocial impact of pediatric NP and CRPS.

Neuropathic pain after surgery - A clinical validation study and assessment of accuracy measures of the 5-item NeuPPS scale.

OBJECTIVE: The aim of this study was to validate the Neuropathic Pain for Post-Surgical Patients (NeuPPS) scale against clinically verified neuropathic pain (NP) by quantitative sensory testing (QST) as well as evaluation of other psychometric properties. The NeuPPS is a validated 5-item scale designed to evaluate NP in surgical populations. METHODS: Data from 537 women aged >18 years scheduled for primary breast cancer surgery enrolled in a previous study for assessing risk factors for persistent pain after breast cancer treatment were used. Exclusion criteria were any other breast surgery or relevant comorbidity. A total of 448 eligible questionnaires were available at 6 months and 455 at 12 months. At 12 months, 290 patients completed a clinical examination and QST. NeuPPS and PainDETECT were analyzed against patients with and without clinically verified NP. NP was assessed using a standardized QST protocol including a clinical assessment. Furthermore, the NeuPPS and PainDETECT scores were psychometrically tested with an item response theory method, the Rasch analysis, to assess construct validity. Primary outcomes were the diagnostic accuracy measures for the NeuPPS, and secondary measures were psychometric analyses of the NeuPPS after 6 and 12 months. PainDETECT was also compared to clinically verified NP as well as NeuPPS comparing the stability of the estimates. RESULTS: Comparing the NeuPPS scores with verified NP using a receiver operating characteristic curve, the NeuPPS had an area under the curve of 0.80. Using a cutoff of 1, the NeuPPS had a sensitivity of 88% and a specificity of 59%, and using a cutoff of 3, the values were 35 and 96%, respectively. Analysis of the PainDETECT indicated that the used cutoffs may be inappropriate in a surgical population. CONCLUSION: The present study supports the validity of the NeuPPS as a screening tool for NP in a surgical population.

Clinical insights into traumatic injury of the inferior alveolar and lingual nerves: a comprehensive approach from diagnosis to therapeutic interventions.

OBJECTIVES: This scoping review explores the risk and management of traumatic injuries to the inferior alveolar and lingual nerves during mandibular dental procedures. Emphasizing the significance of diagnostic tools, the review amalgamates existing knowledge to offer a comprehensive overview. MATERIALS AND METHODS: A literature search across PubMed, Embase, and Cochrane Library informed the analysis. RESULTS: Traumatic injuries often lead to hypo-/anesthesia and neuropathic pain, impacting individuals psychologically and socially. Diagnosis involves thorough anamnesis, clinical-neurological evaluations, and radiographic imaging. Severity varies, allowing for conservative or surgical interventions. Immediate action is recommended for reversible causes, while surgical therapies like decompression, readaptation, or reconstruction yield favorable outcomes. Conservative management, utilizing topical anesthesia, capsaicin, and systemic medications (tricyclic antidepressants, antipsychotics, and serotonin-norepinephrine-reuptake-inhibitors), proves effective for neuropathic pain. CONCLUSIONS: Traumatic nerve injuries, though common in dental surgery, often go unrecorded. Despite lacking a definitive diagnostic gold standard, a meticulous examination of the injury and subsequent impairments is crucial. CLINICAL RELEVANCE: Tailoring treatment to each case's characteristics is essential, recognizing the absence of a universal solution. This approach aims to optimize outcomes, restore functionality, and improve the quality of life for affected individuals.

Anti-Plexin-D1 Seropositive Small Fiber Neuropathy: Clinical Phenotype, Demographics, and Literature Review.

OBJECTIVES: Small fiber neuropathy (SFN) is a subtype of painful neuropathies defined by dysfunction of the Aδ and unmyelinated C fibers. It presents with both neuropathic pain and dysautonomia symptoms, posing a significant diagnostic and therapeutic challenge. To address this challenge, research has been conducted to identify autoantibodies and define their association with phenotypes. METHODS: Eleven cases of anti-plexin-D1 seropositive SFN were reviewed, along with relevant literature, in attempt to better define anti-plexin-D1 SFN demographics, symptoms, associated medical conditions, and therapeutics. RESULTS: Anti-plexin-D1 SFN typically presents in female patients, with neuropathic pain, normal skin biopsy findings, and normal nerve conduction studies. Anti-plexin-D1 shows an association with concurrent chronic pain, with almost half of the patients undergoing an interventional procedure. CONCLUSIONS: Anti-plexin-D1 represents a unique subgroup of SFN, defined by distinct demographics, phenotype, biopsy findings, and therapeutic management.

Peripheral neuropathic pain: supporting patients with self-management.

Peripheral neuropathic pain is a complex condition that can adversely affect people's quality of life. Alongside pharmacological interventions, nurses can support patients to self-manage their pain using non-pharmacological interventions such as lifestyle changes and exercise. To do this effectively, nurses should be able to recognise the signs and symptoms of peripheral neuropathic pain and be able to educate patients on appropriate self-management approaches. It is important that nurses provide education, advice and information in a way that patients can understand and check this understanding. This article provides an overview of how nurses can support patients to self-manage peripheral neuropathic pain by using various non-pharmacological interventions.