Immune Competence and Pain: A Narrative Review.

PURPOSE OF REVIEW: This review aims to summarize current knowledge on the pathophysiology of pain and the role of neuro-immune crosstalk in the development of acute and chronic pain (CP). Specifically, the review focuses on the role of immune cells involved in the innate and acquired immune response, emphasizing their bidirectional interactions with the nervous systems and discussing the implications of this crosstalk on acute and CP management. RECENT FINDINGS: In the last two decades, multiple studies have uncovered the important role of the immune system in initiating, maintaining, and resolving pain stimuli. Furthermore, researchers discovered that the immune system interacts tightly with the nervous system, creating a bidirectional crosstalk in which immune cells influence the response of peripheral and central nerve fibers while neurotransmitters and neuropeptides released by nociceptors directly and indirectly modulate the immune response. The neuro-immune crosstalk in acute and CP is a complex and not fully understood process that comprise the interactions of multiple diverse molecules, bidirectional interferences, and numerous redundant processes. Despite the complexity, important steps have been taken in recent years toward explaining the specific roles of each immune cell type and molecule in the initiation, maintenance and resolution of pain. These findings may set the basis for innovative therapeutic options that target the immune system, overcoming the limitations of current treatments in providing pain relief and the disadvantages associated with opioid therapy.

Primary Sjögren syndrome-related peripheral neuropathy: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Primary Sjögren syndrome (pSS) is a chronic, systemic, autoimmune disorder characterized by lymphocytic infiltrates of the exocrine organs, leading to sicca symptoms and parotid enlargement. pSS has been linked to various neurological manifestations, including peripheral neuropathy (PN). We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS-related PN. METHODS: A literature search in the PubMed database was performed, and 49 papers were eligible to be included in this systematic review and meta-analysis. RESULTS: The pooled prevalence of PN in pSS is estimated to be 15.0% (95% confidence interval = 10.7%-20.7%). The mean age of pSS patients at PN diagnosis is 59 years. Among the patients with pSS and PN, 83% are females. Neuropathic symptoms usually precede or lead to the pSS diagnosis at a 2:1 ratio in patients with pSS-related PN. The commonest type of pSS-related PN is distal axonal polyneuropathy (80% of patients with pSS-related PN), followed by sensory ganglionopathy. Peripheral and cranial mononeuropathies-particularly trigeminal-are also frequent. Risk factors for developing PN include increasing age and presence of vasculitis. Immune-mediated pathogenetic mechanisms are discussed. Glucocorticoids are the most commonly used treatment option for managing pSS-related PN, when associated with vasculitis, followed by the use of intravenous immunoglobulin. CONCLUSIONS: PN is very common in pSS patients. Evidence on long-term prognosis of PN in pSS is limited, and further research is needed. Research into the use of immunosuppressive medication in nonvasculitic neuropathies in the context of pSS merits further consideration.

Restless legs syndrome due to brainstem stroke: A systematic review.

Restless Legs Syndrome (RLS) is a sleep-related movement disorder, which can also result from brainstem pathology. A systematic review of articles published in the electronic databases PubMed and Web of Science was conducted to summarize the existent literature on RLS associated with a brainstem stroke. We identified eight articles including 19 subjects with RLS due to brainstem ischemic lesion. The symptoms occurred simultaneously with the infarction (66.7%) or few days after (33.3%). The most common location of infarction was pons and less commonly medulla. In most cases (68.4%), symptoms were unilateral. In the majority of those cases (92.3%), the contralateral limb was affected due to a lateral pons infarction. RLS symptoms after infarction improved or resolved in almost 90% of cases within a few days up to 3 months. In almost all patients who received dopaminergic treatment (11 out of 13, 91.7%), the symptoms improved significantly or resolved completely. Screening for RLS has to be considered in patients suffering a brainstem stroke, particularly anteromedial pontine infarction. The appearance of acute unilateral RLS symptoms, usually in association with other sensorimotor deficits, should prompt the clinician to consider a vascular event in the brainstem. RLS in these cases seem to have a favorable outcome and respond well to dopaminergic treatment.

Sudomotor dysfunction in patients with gluten neuropathy.

BACKGROUND AND AIM: Gluten neuropathy (GN) is a common neurological manifestation of gluten sensitivity (GS), characterized by serological evidence of GS, while other risk factors for developing neuropathy are absent. The degree of small fiber dysfunction in GN has not been studied in depth to date. Small fiber involvement may lead to pain, thermal perception abnormalities, and sweat gland dysfunction. Sudomotor innervation refers to the cholinergic innervation of the sympathetic nervous system through small fibers in the sweat glands. The aim of our study was to assess the sudomotor function of GN patients. METHODS: Patients with GN were recruited. Clinical and neurophysiological data were obtained. HLA-DQ genotyping was performed. The skin electrochemical conductance (ESC) was measured with SUDOSCANTM. RESULTS: Thirty-two patients (25 males, mean age 69.5±10.2 years) were recruited. Thirteen patients (40.6%) had abnormal sudomotor function of the hands. Sixteen patients (50%) had abnormal sudomotor function of the feet. Twenty-one patients (65.6%) had abnormal sudomotor function of either the hands or feet. Sudomotor dysfunction did not correlate with the type of neuropathy (length-dependent neuropathy or sensory ganglionopathy), gluten-free diet adherence, severity of neuropathy, and duration of disease or HLA-DQ genotype. No differences in the ESC were found between patients with painful and patients with painless GN. CONCLUSION: Sudomotor dysfunction affects two-thirds of patients with GN. The lack of correlation between pain and sudomotor dysfunction suggests different patterns of small fiber involvement in patients with GN.

Chronic idiopathic axonal polyneuropathy: Electrophysiological progression and human leukocyte antigen associations.

BACKGROUND: We aimed to describe the electrophysiological progression rate of chronic idiopathic axonal polyneuropathy (CIAP) and look into the potential role of human leukocyte antigen (HLA) genetic susceptibility in its development. METHODS: We recruited 57 patients with CIAP (mean age at diagnosis 67, mean follow-up 7 years). The assessments included clinical and electrophysiological data and HLA-DQ genotyping. RESULTS: The DQA1*05 allele was found more frequently in patients than in healthy controls (odds ratio, 1.96, P = .011). In patients with length-dependent CIAP, a linear effect of time on the electrophysiological findings was found in the superficial radial (3.2% mean annual decrement, P < .001), sural (4.7% mean annual decrement, P = .002) and tibial nerve (6.1% mean annual decrement, P = .007) amplitudes, independently from age or gender. CONCLUSIONS: Patients with length-dependent CIAP, show a linear progression over time. Interesting associations of HLA-DQA1*05 allele with length-dependent CIAP and non-DQ2/DQ8 with idiopathic sensory ganglionopathy were found. These merit further investigation in larger cohorts and may suggest a role of the immune system in the pathogenesis of CIAP.

Human immunodeficiency virus-related peripheral neuropathy: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Human immunodeficiency virus (HIV)-associated neurological syndromes occur in affected individuals as a consequence of primary HIV infection, opportunistic infections, inflammation and as an adverse effect of some forms of antiretroviral treatment (ART). The aim of this systematic review was to establish the epidemiological characteristics, clinical features, pathogenetic mechanisms and risk factors of HIV-related peripheral neuropathy (PN). METHODS: A systematic, computer-based search was conducted using the PubMed database. Data regarding the above parameters were extracted. Ninety-four articles were included in this review. RESULTS: The most commonly described clinical presentation of HIV neuropathy is the distal predominantly sensory polyneuropathy. The primary pathology in HIVPN appears to be axonal rather than demyelinating. Age and treatment with medications belonging in the nucleoside analogue reverse transcriptase class are risk factors for developing HIV-related neuropathy. The pooled prevalence of PN in patients naïve to ARTs was established to be 29% (95% CI: 9%-62%) and increased to 38% (95% confidence interval [CI]: 29%-48%) when looking into patients at various stages of their disease. More than half of patients with HIV-related neuropathy are symptomatic (53%, 95% CI: 41%-63%). Management of HIV-related neuropathy is mainly symptomatic, although there is evidence that discontinuation of some types of ART, such as didanosine, can improve or resolve symptoms. CONCLUSIONS: Human immunodeficiency virus-related neuropathy is common and represents a significant burden in patients' lives. Our understanding of the disease has grown over the last years, but there are unexplored areas requiring further study.

Evaluation of the 2020 European Academy of Neurology virtual congress: transition from a face-to-face to a virtual meeting.

BACKGROUND AND PURPOSE: Due to the COVID-19 pandemic, scientific congresses are increasingly being organized as virtual congresses (VCs). In May 2020, the European Academy of Neurology (EAN) held a VC, free of charge. In the absence of systematic studies on this topic, the aim of this study is to evaluate the attendance and perceived quality of the 2020 EAN VC compared to the 2019 EAN face-to-face congress (FFC). METHODS: An analysis of the demographic data of participants obtained from the online registration was done. A comparison of the two congresses based on a survey with questions on the perception of speakers' performance, quality of networking and other aspects was made. RESULTS: Of 43,596 registered participants, 20,694 active participants attended the VC. Compared to 2019, the number of participants tripled (6916 in 2019) and the cumulated number of participants attending the sessions was five times higher (169,334 in 2020 vs. 33,024 in 2019). Out of active participants 55% were from outside Europe, 42% were board-certified neurologists (FFC 80%) and 21% were students (FFC 0.6%). The content of the congress was evaluated as 'above expectation' by 56% of the attendees (FFC 41%). Of the respondents who had been exposed to earlier EAN congresses 73% preferred the FFC compared to the VC (17%). CONCLUSION: The VC fulfilled the main mission of organizing high quality EAN congresses despite the restrictions of the impersonal format. The geographical distribution of the participants proves the expected higher inclusivity of a VC. The large participation of students and neurologists in training opens new educational potentials for the EAN.

Local anesthetics counteract cell proliferation and migration of human triple-negative breast cancer and melanoma cells.

In different retrospective studies, a protective role of regional anesthetics in reducing cancer recurrence after surgery was indicated. Accordingly, it has been previously demonstrated a protective effect of anesthetics in breast cancer cells and in other types of cancer. On the other hand, how anesthetics influence cancer needs in-depth investigations. For this purpose, two different human cancer cell lines, MDA-MB-231, triple-negative breast cancer, and A375, melanoma, were used in this study. By means of Western blotting and immunofluorescence and terminal deoxynucleotidyl transferase dUTP nick end labeling analyses, the signal transduction pathways activated by the anesthetics, such as ropivacaine and levobupivacaine, were analyzed. The data obtained demonstrated that both anesthetics are able to counteract cell proliferation by positively modulating cell death signaling and by decreasing cell proliferation and survival pathways.

Alcohol-induced autonomic dysfunction: a systematic review.

PURPOSE: Autonomic dysfunction is a known consequence of chronic and excessive alcohol consumption. The aim of this systematic review was to characterise this phenomenon, describe the frequency at which it occurs and to explore the best management strategies. METHODS: A systematic, computer-based search was conducted using the PubMed database. All studies identified by the search were evaluated independently by at least three authors. For inclusion, studies had to report human subjects consuming ethanol in excess. Case reports and non-original studies were excluded from this review. RESULTS: A total of 55 studies were included in this review. According to cardiovascular reflex tests, 16-73% of chronic alcohol abusers suffer from autonomic dysfunction. The most commonly occurring symptom is erectile dysfunction, whilst other features such as postural dizziness are rare. The most important risk factor for this condition is total lifetime dose of ethanol, although there is mixed evidence supporting the role of other risk factors. The only management strategy currently explored in the literature is abstinence, which appears to lead to significant improvement in autonomic investigations. CONCLUSION: Current literature includes studies of highly heterogeneous populations, consuming differing volumes of alcohol over variable periods of time and utilising a number of different autonomic test batteries and criteria to diagnose autonomic dysfunction. Therefore, further research using homogeneous methods for measuring autonomic dysfunction in the field is needed. Despite this limitation, our review demonstrated that autonomic dysfunction is very common among alcohol abusers.

Safety, Tolerability, and Nocebo Phenomena During Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials.

BACKGROUND: The methodology used for the application of repetitive transcranial magnetic stimulation (TMS) is such that it may induce a placebo effect. Respectively, adverse events (AEs) can occur when using a placebo, a phenomenon called nocebo. The primary aim of our meta-analysis is to establish the nocebo phenomena during TMS. Safety and tolerability of TMS were also studied. METHODS: After a systematic Medline search for TMS randomized controlled trials (RCTs), we assessed the number of patients reporting at least one AE and the number of discontinuations because of AE in active and sham TMS groups. RESULTS: Data were extracted from 93 RCTs. The overall pooled estimate of active TMS and placebo treated patients who discontinued treatment because of AEs was 2.5% (95% CI 1.9%-3.2%) and 2.7% (95% CI 2.0%-3.5%), respectively. The pooled estimate of active TMS and placebo treated patients experiencing at least one AE was 29.3% (95% CI 19.0%-22.6%) and 13.6% (95% CI 11.6%-15.8%), respectively, suggesting that the odds of experiencing an AE is 2.60 times higher (95% CI 1.75-3.86) in the active treatment group compared to placebo (p < 0.00001). The most common AE was headache, followed by dizziness. Secondary meta-analyses in depression and psychotic disorders showed that the odds of experiencing an AE is 3.98 times higher (95% CI 2.14-7.40) and 2.93 times higher (95% CI 1.41-6.07), respectively, in the active treatment groups compared to placebo. CONCLUSIONS: TMS is a safe and well-tolerated intervention. Nocebo phenomena do occur during TMS treatment and should be acknowledged during clinical trial design and daily clinical practice.

Ultrasound Assessment of Extracranial Carotids and Vertebral Arteries in Acute Cerebral Ischemia.

Assessing ischemic etiology and mechanism during the acute phase of an ischemic stroke is crucial in order to tailor and monitor appropriate treatment and determine prognosis. Cervical Duplex Ultrasound (CDU) has evolved since many years as an excellent screening tool for the evaluation of extracranial vasculature. CDU has the advantages of a low cost, easily applicable, bed side examination with high temporal and spatial resolution and without exposing the patients to any significant complications. It represents an easily repeatable test that can be performed in the emergency room as a first-line examination of cervical artery pathology. CDU provides well validated estimates of the type of the atherosclerotic plaque, the degree of stenosis, as well as structural and hemodynamic information directly about extracranial vessels (e.g., subclavian steal syndrome) and indirectly about intracranial circulation. CDU may also aid the diagnosis of non-atherosclerotic lesions of vessel walls including dissections, arteritis, carotid-jugular fistulas and fibromuscular dysplasias. The present narrative review outlines all potential applications of CDU in acute stroke management and also highlights its potential therapeutic implications.

Neurologic Deficits in Patients With Newly Diagnosed Celiac Disease Are Frequent and Linked With Autoimmunity to Transglutaminase 6.

BACKGROUND & AIMS: Celiac disease is an autoimmune disorder induced by ingestion of gluten that affects 1% of the population and is characterized by gastrointestinal symptoms, weight loss, and anemia. We evaluated the presence of neurologic deficits and investigated whether the presence of antibodies to Transglutaminase 6 (TG6) increases the risk of neurologic defects in patients with a new diagnosis of celiac disease. METHODS: We performed a prospective cohort study at a secondary-care gastroenterology center of 100 consecutive patients who received a new diagnosis of celiac disease based on gastroscopy and duodenal biopsy. We collected data on neurologic history, and patients were evaluated in a clinical examination along with magnetic resonance imaging of the brain, magnetic resonance (MR) spectroscopy of the cerebellum, and measurements of antibodies against TG6 in serum samples. The first 52 patients recruited underwent repeat MR spectroscopy at 1 year after a gluten-free diet (GFD). The primary aim was to establish if detection of antibodies against TG6 can be used to identify patients with celiac disease and neurologic dysfunction. RESULTS: Gait instability was reported in 24% of the patients, persisting sensory symptoms in 12%, and frequent headaches in 42%. Gait ataxia was found in 29% of patients, nystagmus in 11%, and distal sensory loss in 10%. Sixty percent of patients had abnormal results from magnetic resonance imaging, 47% had abnormal results from MR spectroscopy of the cerebellum, and 25% had brain white matter lesions beyond that expected for their age group. Antibodies against TG6 were detected in serum samples from 40% of patients-these patients had significant atrophy of subcortical brain regions compared with patients without TG6 autoantibodies. In patients with abnormal results from MR spectroscopy of the cerebellum, those on the GFD had improvements detected in the repeat MR spectroscopy 1 year later. CONCLUSIONS: In a prospective cohort study of patients with a new diagnosis of celiac disease at a gastroenterology clinic, neurologic deficits were common and 40% had circulating antibodies against TG6. We observed a significant reduction in volume of specific brain regions in patients with TG6 autoantibodies, providing evidence for a link between autoimmunity to TG6 and brain atrophy in patients with celiac disease. There is a need for early diagnosis, increased awareness of the neurologic manifestations among clinicians, and reinforcement of adherence to a strict GFD by patients to avoid permanent neurologic disability.

Electrophysiological determinants of the clinical severity of axonal peripheral neuropathy.

INTRODUCTION: Electrophysiological diagnosis of axonal peripheral neuropathy (PN) is based on the attenuated amplitudes of nerve conduction studies (NCS), or a reduced sural/radial amplitude ratio (SRAR). We aimed to identify the electrophysiological determinants of the clinical severity of PN. METHODS: Patients with chronic axonal PN underwent detailed NCS. The clinical severity of PN was determined based upon the overall neuropathy limitations scale (ONLS). RESULTS: Ninety-five patients (71.6% males, mean age 71.9 ± 9.0 years) were recruited. Significant correlations were observed between the radial sensory nerve action potential (SNAP) and the ONLS total score (Spearman's rho -0.382, p < 0.001); and between the tibial compound muscle action potential and the ONLS leg score (Spearman's rho -0.283, p = 0.005). No correlations between the SRAR and the ONLS scores were found. DISCUSSION: The radial SNAP is the strongest electrophysiological determinant of PN severity and might be useful for monitoring disease progression or response to treatment. Muscle Nerve 59:491-493, 2019.

Non-Motor Symptoms Assessed by Non-Motor Symptoms Questionnaire and Non-Motor Symptoms Scale in Parkinson's Disease in Selected Asian Populations.

BACKGROUND: Ethnic variations have been described in medical conditions, such as hypertension, diabetes, and multiple sclerosis. Whether ethnicity plays a role in Parkinson's disease (PD), particularly with regard to non-motor symptoms (NMS), remains unclear. Existing literature is diverse, controversial, and inadequately documented. This review aims to analyse and report the currently available literature on NMS, specifically in Asian PD patients. SUMMARY: We conducted a literature review using PubMed, searching for articles and currently available publications that reference and assess NMS in PD patients living in Asia using the validated NMS Questionnaire (NMS Quest) and NMS Scale (NMSS). In total, 24 articles were included: 12 using the NMS Quest and 12 using the NMSS. Symptoms of constipation, memory impairment, and nocturia were the most frequently self-reported symptoms (NMS Quest) in selected Asian populations, while symptoms within the domains sleep/fatigue, attention/memory, and mood/apathy were most prevalent when applying the health-professional completed NMSS. Key Messages: NMS are generally prevalent and highly burdensome within selected Asian PD populations living in countries included in this review. Our review suggests that NMS-driven phenotypic heterogeneity is present in Asian patients, and compared to Western PD populations there might be variations in assessed NMS.

Validation of the Greek Version of the Fibromyalgia Rapid Screening Tool.

BACKGROUND AND AIM: The Fibromyalgia Rapid Screening Tool (FiRST) is a brief, simple, and straightforward self-administered questionnaire that was developed by Perrot et al. for the detection of fibromyalgia syndrome in patients with diffuse chronic pain. The aim of our study was to develop and validate the Greek version of FiRST. METHODS: The study was set up as a prospective observational study. The original French version of FiRST was adapted into Greek using forward and backward translation. Patients with chronic diffuse pain with a clinical diagnosis of fibromyalgia and osteoarthritis based on the criteria of the American College of Rheumatology were invited to participate to the study. RESULTS: Of the 101 patients who met our inclusion criteria, 42 were diagnosed with fibromyalgia and 59 with osteoarthritis. The 2 groups did not differ significantly regarding gender and pain characteristics (duration, intensity). Cronbach's alpha coefficient was 0.79. Receiver operating characteristic analysis showed an area under the curve of 89% (95% confidence interval = 83 to 95%; SE: 0.032, P < 0.001). At a cutoff score of ≥ 5, FiRST showed a sensitivity of 86%, a specificity of 83%, a positive predictive value of 78%, and a negative predictive value of 89%. The intraclass coefficient for the test-retest reliability was 0.96. CONCLUSION: The Greek version of FiRST is a valid screening tool for fibromyalgia in daily practice.

Herpes Simplex Virus Type 2 Encephalitis as a Cause of Ischemic Stroke: Case Report and Systematic Review of the Literature.

BACKGROUND AND AIM: Our objective is to describe a patient who developed an ischemic stroke as a complication of herpes simplex virus type 2 (HSV-2) encephalitis and to review the literature. PATIENTS AND METHODS: A 45-year-old immune-competent Caucasian man presented with a 24-hour history of confusion and fever, and following clinical and laboratory examination was diagnosed with HSV-2 encephalitis. However, the brain magnetic resonance imaging also showed an acute ischemic infarct in the left frontal lobe corresponding to vascular territories of middle cerebral artery branches. Further screening failed to identify any other cause of the stroke. A systematic literature search was conducted in February 2015 using the PubMed database. RESULTS: Six more cases of herpes simplex virus (HSV) central nervous system (CNS) infection that developed a definite ischemic stroke as a complication of the infection were identified. CONCLUSIONS: Ischemic stroke, although infrequent, can complicate the evolution of herpes simplex meningitis or encephalitis. Clinicians should include HSV CNS infection as a possible cause of ischemic stroke, especially in young patients with ischemic stroke of unknown etiology.

From basilar artery dolichoectasia to basilar artery aneurysm: natural history in images.

Dolichoectasia is a medical term used to describe elongated and dilated vessels that follow a tortuous and windy course with frequent loops and curves. We are presenting the natural history in images of a normal basilar artery becoming dolichoectatic, followed by the formation of an aneurysm, over a period of many years, in 60-year-old Caucasian man with a long history of secondary progressive multiple sclerosis and uncontrolled arterial hypertension, who was diagnosed with dolichoectasia of basilar artery in 2008. Although relatively stable at this point, eventually his mobility deteriorated and signs from the cranial nerves, such as trigeminal neuralgia and bilateral palsy of the VI and the VII nerves were added in the clinical picture. In 2014, both computed tomography and magnetic resonance imaging of the brain revealed the formation of an unruptured aneurysm of the basilar artery.

Factors associated with mental health status of medical residents: a model-guided study.

Residency is a stressful period in a physician's development, characterized by long work hours, time pressure, and excessive work load, that can exert negative effects on residents' mental health. Job burnout and negative work-home interference may play a major role in residents' mental health problems. The present study used the job demands-resources model as a theoretical framework to examine the way in which job demands (e.g., workload, emotional demands) and job resources (e.g., supervisor support, job autonomy) were associated with residents' mental health. From a pool of 290 medical residents, 264 (91 %) completed the questionnaires. Applying structural equation modeling techniques, the results showed that greater emotional exhaustion (ß = -.65, SE = .09, p < .001) and more work-home interference (ß = -.26, SE = .10, p < .05) were related to poor mental health. Specific job demands (i.e., high workload) and particular job resources (i.e., low opportunities for professional development and low supervisor support) were related to poor mental health not directly but only indirectly, via emotional exhaustion or work-home interference. Thus, through work-related emotional exhaustion, the impact of work conditions might be transmitted to and interfere with non-work related domains such as family life, as well as with domain-unspecific aspects of well-being, such as mental health and psychological distress. Implications of the results and suggestions for future research and practice are outlined.

Validation of the Greek Version of the DN4 Diagnostic Questionnaire for Neuropathic Pain.

BACKGROUND: The Douleur Neuropathique 4 questionnaire (DN4) was developed by the French Neuropathic Pain Group and is a simple and objective tool, primarily designed to screen for neuropathic pain. The aim of our study is to validate the DN4 in the Greek language. METHODS: The study was set up as a prospective observational study. Two pain specialists independently examined patients and diagnosed them with neuropathic, nociceptive, or mixed pain, according to the International Association for the Study of Pain (IASP) definitions. A third and a fourth physician administered the DN4 questionnaire to the patients. RESULTS: Out of the 237 patients who met our inclusion criteria and had identical diagnoses regarding the type of pain, 123 were diagnosed with neuropathic, 59 with nociceptive, and 55 with mixed pain. Among patients with identical diagnoses of neuropathic or nociceptive pain, using a receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) was 0.92. A cutoff point of equal or greater than 4 resulted in a sensitivity of 93% and a specificity of 78%. Among patients suffering from pain with neuropathic element (neuropathic or mixed pain) or pain with no neuropathic element (nociceptive pain), using a ROC curve analysis, the AUC was 0.89. A cutoff point of equal or greater than 4 resulted in a sensitivity of 89% and a specificity of 78%. CONCLUSION: The Greek version of DN4 is a valid tool for discriminating between neuropathic and nociceptive pain conditions in daily practice.