[The EAN-NeuPSIG guideline on the diagnosis of neuropathic pain-a summary]. / Die EAN-NeuPSIG-Leitlinie zur Diagnostik bei neuropathischen Schmerzen ­ eine Kurzfassung.

In this joint guideline of the scientific societies and working groups mentioned in the title, evidence-based recommendations for the use of screening questionnaires and diagnostic tests in patients with neuropathic pain were developed. The systematic literature search and meta-analysis yielded the following results: Of the screening questionnaires, Douleur Neuropathique en 4 Questions (DN4), I­DN4 (self-administered DN4), and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) received a strong recommendation, while S­LANSS (self-administered LANSS) and PainDETECT received weak recommendations for their use in the diagnostic workup of patients with possible neuropathic pain. There was a strong recommendation for the use of skin biopsy and a weak recommendation for quantitative sensory testing and nociceptive evoked potentials. The role of confocal corneal microscopy is still unclear. Functional imaging and peripheral nerve blocks are helpful in elucidating the pathophysiology, but current literature does not support their use in diagnosing neuropathic pain. In selected cases, genetic testing in specialized centers may be considered.

The role of cytokines and chemokines in the maintenance of chronic pain-a pilot study.

Introduction: The immune system is believed to be important in the initiation and maintenance of chronic pain. Objectives: The aim was to investigate whether patients with chronic painful polyneuropathy (PP) differ in cytokine profiles of serum and/or cerebrospinal fluid (CSF) compared with pain-free controls. Methods: Thirty-nine patients (16 women and 23 men, mean age, 69.2 ± 12.7 years, range 41-92 years) with PP (mean duration 43 ± 48.3 months) were phenotyped with quantitative sensory testing and electroneurography, and serum and CSF samples were analyzed by 40-multiplexed, bead-based cytokine immunoassays. Results were compared with 36 age- and gender-matched patients with normal pressure hydrocephalus and absence of abnormal CSF findings. Results: Compared with controls, patients with PP had lower concentrations of several proinflammatory and anti-inflammatory chemokines and cytokines in CSF, and others showed the same tendency, among these were tumor necrosis factor-α (14.1 ± 10.0 vs 23.9 ± 16.4 pg/mL, P < 0.005), interleukin (IL)-2 (0.6 ± 0.4 vs 1.2 ± 0.6 pg/mL, P < 0.0001), IL-6 (4.7 ± 6.8 vs 7.3 ± 9 pg/mL, P = 0.001), and IL-10 (7.5 ± 6.8 vs 16.8 ± 19.2 pg/mL, P < 0.01), whereas no differences were observed in serum. Conclusion: Results suggest that (1) inflammatory mediators play a minor role in the maintenance of chronic pain in contrast to initiation of acute pain, (2) chemokines/cytokines are downregulated in chronic pain, or (3) chemokines/cytokines have a protective role for nerve regeneration that is disturbed in patients with chronic pain.

Efficacy and safety of eliapixant in diabetic neuropathic pain and prediction of placebo responders with an exploratory novel algorithm: results from the randomized controlled phase 2a PUCCINI study.

ABSTRACT: Phase 2a of the PUCCINI study was a placebo-controlled, double-blind, parallel-group, multicenter, proof-of-concept study evaluating the efficacy and safety of the selective P2X3 antagonist eliapixant in patients with diabetic neuropathic pain (DNP) ( ClinicalTrials.gov NCT04641273). Adults with type 1 or type 2 diabetes mellitus with painful distal symmetric sensorimotor neuropathy of >6 months' duration and neuropathic pain were enrolled and randomized 1:1 to 150 mg oral eliapixant twice daily or placebo for 8 weeks. The primary endpoint was change from baseline in weekly mean 24-hour average pain intensity score at week 8. In total, 135 participants completed treatment, 67 in the eliapixant group and 68 in the placebo group. At week 8, the change from baseline in posterior mean 24-hour average pain intensity score (90% credible interval) in the eliapixant group was -1.56 (-1.95, -1.18) compared with -2.17 (-2.54, -1.80) for the placebo group. The mean treatment difference was 0.60 (0.06, 1.14) in favor of placebo. The use of a model-based framework suggests that various factors may contribute to the placebo-responder profile. Adverse events were mostly mild or moderate in severity and occurred in 51% of the eliapixant group and 48% of the placebo group. As the primary endpoint was not met, the PUCCINI study was terminated after completion of phase 2a and did not proceed to phase 2b. In conclusion, selective P2X3 antagonism in patients with DNP did not translate to any relevant improvement in different pain intensity outcomes compared with placebo. Funding: Bayer AG.

Paradoxical heat sensation as a manifestation of thermal hypesthesia: a study of 1090 patients with lesions of the somatosensory system.

ABSTRACT: Paradoxical heat sensation (PHS) is the perception of warmth when the skin is cooled. Paradoxical heat sensation rarely occurs in healthy individuals but more frequently in patients suffering from lesions or disease of the peripheral or central nervous system. To further understand mechanisms and epidemiology of PHS, we evaluated the occurrence of PHS in relation to disease aetiology, pain levels, quantitative sensory testing parameters, and Neuropathic Pain Symptom Inventory (NPSI) items in patients with nervous system lesions. Data of 1090 patients, including NPSI scores from 404 patients, were included in the analysis. We tested 11 quantitative sensory testing parameters for thermal and mechanical detection and pain thresholds, and 10 NPSI items in a multivariate generalised linear model with PHS, aetiology, and pain (yes or no) as fixed effects. In total, 30% of the neuropathic patients reported PHS in contrast to 2% of healthy individuals. The frequency of PHS was not linked to the presence or intensity of pain. Paradoxical heat sensation was more frequent in patients living with polyneuropathy compared with central or unilateral peripheral nerve lesions. Patients who reported PHS demonstrated significantly lower sensitivity to thermal perception, with lower sensitivity to normally painful heat and cold stimuli. Neuropathic Pain Symptom Inventory scores were lower for burning and electric shock-like pain quality for patients with PHS. Our findings suggest that PHS is associated with loss of small thermosensory fibre function normally involved in cold and warm perception. Clinically, presence of PHS could help screening for loss of small fibre function as it is straightforward to measure or self-reported by patients.

Developing consensus on core outcome sets of domains for acute, the transition from acute to chronic, recurrent/episodic, and chronic pain: results of the INTEGRATE-pain Delphi process.

Background: Pain is the leading cause of disability worldwide among adults and effective treatment options remain elusive. Data harmonization efforts, such as through core outcome sets (COS), could improve care by highlighting cross-cutting pain mechanisms and treatments. Existing pain-related COS often focus on specific conditions, which can hamper data harmonization across various pain states. Methods: Our objective was to develop four overarching COS of domains/subdomains (i.e., what to measure) that transcend pain conditions within different pain categories. We hosted a meeting to assess the need for these four COS in pain research and clinical practice. Potential COS domains/subdomains were identified via a systematic literature review (SLR), meeting attendees, and Delphi participants. We conducted an online, three step Delphi process to reach a consensus on domains to be included in the four final COS. Survey respondents were identified from the SLR and pain-related social networks, including multidisciplinary health care professionals, researchers, and people with lived experience (PWLE) of pain. Advisory boards consisting of COS experts and PWLE provided advice throughout the process. Findings: Domains in final COS were generally related to aspects of pain, quality of life, and physical function/activity limitations, with some differences among pain categories. This effort was the first to generate four separate, overarching COS to encourage international data harmonization within and across different pain categories. Interpretation: The adoption of the COS in research and clinical practice will facilitate comparisons and data integration around the world and across pain studies to optimize resources, expedite therapeutic discovery, and improve pain care. Funding: Innovative Medicines Initiative 2 Join Undertaking; European Union Horizon 2020 research innovation program, European Federation of Pharmaceutical Industries and Associations (EFPIA) provided funding for IMI-PainCare. RDT acknowledges grants from Esteve and TEVA.

The association of self-reported symptoms of central sensitization and sleep disturbances in neuropathic pain.

Introduction: Patients with neuropathic pain (NP) report a higher impairment of quality of life and sleep than patients with chronic pain without neuropathic characteristics. These include somatosensory peculiarities like allodynia, a surrogate marker for central sensitization. Objectives: This study aimed to investigate the relation between symptoms of central sensitization and sleep disturbances in patients with NP. Methods: Within this cross-sectional study, data sets of 3339 patients with chronic NP syndromes (painful diabetic polyneuropathy, n = 543; postherpetic neuralgia, n = 1480) or complex regional pain syndromes (CRPS, n = 1316) were analyzed. Neuropathic pain symptoms were assessed with the painDETECT questionnaire (PD-Q), depression with the Patient Health Questionnaire-9, and sleep impairment with items of the Medical Outcomes Study Sleep Scale in 4 subscales. The association of demographic/clinical data, somatosensory phenotype, depression, and pain intensity with sleep impairment was assessed by unadjusted Spearman correlation analyses and multivariable regression analyses. Results: Sleep impairment was observed in all pain aetiologies although with some significant differences in the single sleep items. The intensity of the individual PD-Q items differed to some extent between the 3 pain entities, whereas the PD-Q sum score was similar. Thermal hyperalgesia and burning assessed by the PD-Q were significantly associated with sleep disturbance, adequacy, and quantity but not with sleep somnolence. Only depression and self-reported allodynia had a significant relation to all 4 sleep elements. Conclusion: Beside depression, allodynia as a surrogate marker hints to a possible impact of central sensitization on the sleep disruption of patients with NP.

Varicella Zoster Virus-Specific Hyperimmunoglobulin in the Adjuvant Treatment of Immunocompromised Herpes Zoster Patients: A Case Series.

INTRODUCTION: Immunocompromised patients are at increased risk for herpes zoster (HZ)-associated complications. Despite standard therapy with systemic antiviral drugs and analgesics, complications are frequently encountered, including generalization of lesions or persistent neuropathic pain, so-called post-herpetic neuralgia (PHN). Given the scarcity of literature and awareness of therapeutic options to improve patient outcomes, especially for vulnerable patient groups, here we describe a strategy based on early intensification of treatment with a varicella zoster virus-specific hyperimmunoglobulin (VZV-IgG), which is approved in the adjuvant treatment of HZ. METHODS: For this case series, we selected four cases of HZ in patients with impaired immunity due to hemato-oncologic disease or immunosuppressive treatment who presented with either existing generalized lesions and/or severe pain or with other risk factors for a complicated HZ course such as PHN. They were considered to be representative examples of different patient profiles eligible for intensification of treatment by the addition of VZV-IgG to virostatic therapy. CASE REPORT: All patients showed a rapid response to combined treatment with VZV-IgG and a virostatic agent. In two patients who had generalized lesions, the formation of new lesions ceased 1 day after VZV-IgG infusion. One patient, with mantle cell lymphoma, achieved complete healing of the lesions 9 days after diagnosis of HZ, a rare occurrence compared to similar cases or cohorts. A patient with HZ in the cervical region showed a good response after a single dose of VZV-IgG. None of the patients developed post-zoster-related complications. Combination therapy of a virostatic agent and VZV-IgG was well tolerated in these four cases. CONCLUSION: This case series demonstrates highly satisfactory treatment effectiveness and tolerability for VZV-IgG in the adjuvant treatment of immunocompromised HZ patients and supports early intensification of HZ therapy in patients at high risk of severe disease progression.

Beyond biopsychosocial: The keystone mechanism theory of pain.

Pain is a deeply personal experience, with interindividual differences in its chronification and treatment presenting a formidable healthcare challenge. The biopsychosocial model (BPSm) has been hugely influential within nascent attempts at precision pain medicine, steering the field away from a reductionist biomechanical viewpoint and emphasising complex interactions of biological, psychological, and social factors which shape the individuality of pain. However, despite offering a strong theoretical foundation and holistic perspective, we contend that the BPSm remains limited in its capacity to deliver truly mechanistically informed treatment of pain. We therefore propose the keystone model of pain which offers a pragmatic balance between the dimensionality expansive BPSm and overly reductive approaches, providing both theoretical and practical advantages for the transition from treating populations to individual people.

Precision Medicine in Neuropathic Pain.

Neuropathic pain is a common chronic pain condition that is caused by a lesion or disease of the somatosensory nervous system. The multitude of sensory negative and positive sensations and associated comorbidities have a major impact on quality of life of affected patients. Current treatment options often only lead to a partial pain relief or are even completely ineffective. In addition, many clinical trials for the development of new drugs have not met the primary endpoint. Therefore, there is still an unmet clinical need in neuropathic pain syndromes. One reason for this therapeutic dilemma could be the heterogeneity of neuropathic pain with a variety of pathophysiological pain mechanisms that are expressed differently in each patient regardless of the underlying disease etiology. Reclassification of neuropathic pain syndromes therefore focuses on the underlying mechanisms of pain development rather than the disease etiology. A priori stratification of patients based on these individual mechanisms could allow the identification of potential treatment responders and thus realize the concept of a mechanism-based treatment. As no biomarkers for pain mechanisms have been discovered yet, one has to rely on surrogate markers that are thought to be closely related to these mechanisms. In this chapter, we present promising predictive biomarkers, focusing in particular on sensory symptoms and signs assessed by patient-reported outcome measures and sensory testing, and discuss how these tools might be used in clinical trials in the future.

Cutaneous nerve fiber and peripheral Nav1.7 assessment in a large cohort of patients with postherpetic neuralgia.

ABSTRACT: The mechanisms of pain in postherpetic neuralgia (PHN) are still unclear, with some studies showing loss of cutaneous sensory nerve fibers that seemed to correlate with pain level. We report results of skin biopsies and correlations with baseline pain scores, mechanical hyperalgesia, and the Neuropathic Pain Symptom Inventory (NPSI) in 294 patients who participated in a clinical trial of TV-45070, a topical semiselective sodium 1.7 channel (Nav1.7) blocker. Intraepidermal nerve fibers and subepidermal Nav1.7 immunolabeled fibers were quantified in skin punch biopsies from the area of maximal PHN pain, as well as from the contralateral, homologous (mirror image) region. Across the entire study population, a 20% reduction in nerve fibers on the PHN-affected side compared with that in the contralateral side was noted; however, the reduction was much higher in older individuals, approaching 40% in those aged 70 years or older. There was a decrease in contralateral fiber counts as well, also noted in prior biopsy studies, the mechanism of which is not fully clear. Nav1.7-positive immunolabeling was present in approximately one-third of subepidermal nerve fibers and did not differ on the PHN-affected vs contralateral sides. Using cluster analysis, 2 groups could be identified, with the first cluster showing higher baseline pain, higher NPSI scores for squeezing and cold-induced pain, higher nerve fiber density, and higher Nav1.7 expression. While Nav1.7 varies from patient to patient, it does not seem to be a key pathophysiological driver of PHN pain. Individual differences in Nav1.7 expression, however, may determine the intensity and sensory aspects of pain.

Joint European Academy of Neurology-European Pain Federation-Neuropathic Pain Special Interest Group of the International Association for the Study of Pain guidelines on neuropathic pain assessment.

BACKGROUND AND PURPOSE: In these guidelines, we aimed to develop evidence-based recommendations for the use of screening questionnaires and diagnostic tests in patients with neuropathic pain (NeP). METHODS: We systematically reviewed studies providing information on the sensitivity and specificity of screening questionnaires, and quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy. We also analysed how functional neuroimaging, peripheral nerve blocks, and genetic testing might provide useful information in diagnosing NeP. RESULTS: Of the screening questionnaires, Douleur Neuropathique en 4 Questions (DN4), I-DN4 (self-administered DN4), and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) received a strong recommendation, and S-LANSS (self-administered LANSS) and PainDETECT weak recommendations for their use in the diagnostic pathway for patients with possible NeP. We devised a strong recommendation for the use of skin biopsy and a weak recommendation for quantitative sensory testing and nociceptive evoked potentials in the NeP diagnosis. Trigeminal reflex testing received a strong recommendation in diagnosing secondary trigeminal neuralgia. Although many studies support the usefulness of corneal confocal microscopy in diagnosing peripheral neuropathy, no study specifically investigated the diagnostic accuracy of this technique in patients with NeP. Functional neuroimaging and peripheral nerve blocks are helpful in disclosing pathophysiology and/or predicting outcomes, but current literature does not support their use for diagnosing NeP. Genetic testing may be considered at specialist centres, in selected cases. CONCLUSIONS: These recommendations provide evidence-based clinical practice guidelines for NeP diagnosis. Due to the poor-to-moderate quality of evidence identified by this review, future large-scale, well-designed, multicentre studies assessing the accuracy of diagnostic tests for NeP are needed.

Recommendations for terminology and the identification of neuropathic pain in people with spine-related leg pain. Outcomes from the NeuPSIG working group.

ABSTRACT: Pain radiating from the spine into the leg is commonly referred to as "sciatica," "Sciatica" may include various conditions such as radicular pain or painful radiculopathy. It may be associated with significant consequences for the person living with the condition, imposing a reduced quality of life and substantial direct and indirect costs. The main challenges associated with a diagnosis of "sciatica" include those related to the inconsistent use of terminology for the diagnostic labels and the identification of neuropathic pain. These challenges hinder collective clinical and scientific understanding regarding these conditions. In this position paper, we describe the outcome of a working group commissioned by the Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain (IASP) which was tasked with the following objectives: (1) to revise the use of terminology for classifying spine-related leg pain and (2) to propose a way forward on the identification of neuropathic pain in the context of spine-related leg pain. The panel recommended discouraging the term "sciatica" for use in clinical practice and research without further specification of what it entails. The term "spine-related leg pain" is proposed as an umbrella term to include the case definitions of somatic referred pain and radicular pain with and without radiculopathy. The panel proposed an adaptation of the neuropathic pain grading system in the context of spine-related leg pain to facilitate the identification of neuropathic pain and initiation of specific management in this patient population.

Turning When Using Smartphone in Persons With and Those Without Neurologic Conditions: Observational Study.

BACKGROUND: Turning during walking is a relevant and common everyday movement and it depends on a correct top-down intersegmental coordination. This could be reduced in several conditions (en bloc turning), and an altered turning kinematics has been linked to increased risk of falls. Smartphone use has been associated with poorer balance and gait; however, its effect on turning-while-walking has not been investigated yet. This study explores turning intersegmental coordination during smartphone use in different age groups and neurologic conditions. OBJECTIVE: This study aims to evaluate the effect of smartphone use on turning behavior in healthy individuals of different ages and those with various neurological diseases. METHODS: Younger (aged 18-60 years) and older (aged >60 years) healthy individuals and those with Parkinson disease, multiple sclerosis, subacute stroke (<4 weeks), or lower-back pain performed turning-while-walking alone (single task [ST]) and while performing 2 different cognitive tasks of increasing complexity (dual task [DT]). The mobility task consisted of walking up and down a 5-m walkway at self-selected speed, thus including 180° turns. Cognitive tasks consisted of a simple reaction time test (simple DT [SDT]) and a numerical Stroop test (complex DT [CDT]). General (turn duration and the number of steps while turning), segmental (peak angular velocity), and intersegmental turning parameters (intersegmental turning onset latency and maximum intersegmental angle) were extracted for head, sternum, and pelvis using a motion capture system and a turning detection algorithm. RESULTS: In total, 121 participants were enrolled. All participants, irrespective of age and neurologic disease, showed a reduced intersegmental turning onset latency and a reduced maximum intersegmental angle of both pelvis and sternum relative to head, thus indicating an en bloc turning behavior when using a smartphone. With regard to change from the ST to turning when using a smartphone, participants with Parkinson disease reduced their peak angular velocity the most, which was significantly different from lower-back pain relative to the head (P<.01). Participants with stroke showed en bloc turning already without smartphone use. CONCLUSIONS: Smartphone use during turning-while-walking may lead to en bloc turning and thus increase fall risk across age and neurologic disease groups. This behavior is probably particularly dangerous for those groups with the most pronounced changes in turning parameters during smartphone use and the highest fall risk, such as individuals with Parkinson disease. Moreover, the experimental paradigm presented here might be useful in differentiating individuals with lower-back pain without and those with early or prodromal Parkinson disease. In individuals with subacute stroke, en bloc turning could represent a compensative strategy to overcome the newly occurring mobility deficit. Considering the ubiquitous smartphone use in daily life, this study should stimulate future studies in the area of fall risk and neurological and orthopedic diseases. TRIAL REGISTRATION: German Clinical Trials Register DRKS00022998; https://drks.de/search/en/trial/DRKS00022998.

Differential Expression of microRNAs in Serum of Patients with Chronic Painful Polyneuropathy and Healthy Age-Matched Controls.

Polyneuropathies (PNP) are the most common type of disorder of the peripheral nervous system in adults. However, information on microRNA expression in PNP is lacking. Following microRNA sequencing, we compared the expression of microRNAs in the serum of patients experiencing chronic painful PNP with healthy age-matched controls. We have been able to identify four microRNAs (hsa-miR-3135b, hsa-miR-584-5p, hsa-miR-12136, and hsa-miR-550a-3p) that provide possible molecular links between degenerative processes, blood flow regulation, and signal transduction, that eventually lead to PNP. In addition, these microRNAs are discussed regarding the targeting of proteins that are involved in high blood flow/pressure and neural activity dysregulations/disbalances, presumably resulting in PNP-typical symptoms such as chronical numbness/pain. Within our study, we have identified four microRNAs that may serve as potential novel biomarkers of chronic painful PNP, and that may potentially bear therapeutic implications.

Test-retest reliability of a simple bedside-quantitative sensory testing battery for chronic neuropathic pain.

Introduction: The sensory phenotype is believed to provide information about the underlying pathophysiological mechanisms and to be used in the diagnosis and treatment of chronic neuropathic pain. However, the use of standardized quantitative sensory testing (QST) protocols is limited due to high expenditures of time and costs. Thus, a simple bedside-QST battery was recently developed showing good agreement when compared with laboratory QST. The aim of this study was to preliminary validate this bedside-QST protocol. Methods: Patients experiencing chronic pain with neuropathic features (n = 60) attended 3 visits. During the first visit, laboratory QST and bedside-QST were performed by the same trained investigator. Three hours and 3 weeks later, bedside-QST was repeated. Patients completed questionnaires regarding their pain (intensity, quality), depression/anxiety, and quality of life. Test-retest reliability and convergent/divergent validity were investigated. Results: Most of the bedside-QST parameters, including also those recommended in our first study as being indicative for sensory phenotypes, revealed a moderate to excellent test-retest reliability. Overall, results for short-term reliability and interval-scaled parameters were slightly better. Most of the bedside-QST parameters did not correlate with the depression and anxiety score, suggesting a good divergent validity. Conclusions: Bedside-QST has good criterion and divergent validity as well as reliability. This battery consists of 5 low-cost devices that can be quickly and easily used to characterize the sensory phenotype of patients with neuropathic pain. A combination of bedside-QST parameters can be used to investigate patients' subgroups with specific pathophysiological mechanisms and to identify treatment responders.

Maximizing treatment efficacy through patient stratification in neuropathic pain trials.

Treatment of neuropathic pain remains inadequate despite the elucidation of multiple pathophysiological mechanisms and the development of promising therapeutic compounds. The lack of success in translating knowledge into clinical practice has discouraged pharmaceutical companies from investing in pain medicine; however, new patient stratification approaches could help bridge the translation gap and develop individualized therapeutic approaches. As we highlight in this article, subgrouping of patients according to sensory profiles and other baseline characteristics could aid the prediction of treatment success. Furthermore, novel outcome measures have been developed for patients with neuropathic pain. The extent to which sensory profiles and outcome measures can be employed in routine clinical practice and clinical trials and across distinct neuropathic pain aetiologies is yet to be determined. Improvements in animal models, drawing on our knowledge of human pain, and robust public-private partnerships will be needed to pave the way to innovative and effective pain medicine in the future.

Patient Reported Outcome Measures in Chronic Neuropathic Pain Clinical Trials - A Systematic Literature Review.

In neuropathic pain clinical trials, the patient's perspective is often insufficiently reflected focusing mainly on pain intensity. Comparability of outcome assessment is limited due to heterogenous patient reported outcome measures (PROMs). The MEDLINE, CENTRAL, and Embase databases and reference lists of published meta-analyses were searched. Randomized controlled studies assessing treatment efficacy of drugs for chronic neuropathic pain were included. PROMs were assigned to recommended IMMPACT/NeuPSIG domains: pain intensity, pain other aspects, physical functioning, emotional functioning, global improvement and satisfaction, adverse events, participant disposition. Domains and PROMs were compared regarding the publication year and methodological quality of the studies. Within the 251 included studies 200 PROMs were used with 27 being recommended by IMMPACT/NeuPSIG. The number of domains was higher in high/moderate quality studies. The (sub-) domains 'physical functioning', 'global improvement and satisfaction', and 'neuropathic pain quality' were assessed more frequently in high/moderate quality studies and those published after 2011. Recent studies and those of better quality more often used the recommended PROMs. Although neuropathic assessment via PROMs has improved, there is still a high heterogeneity. A standardized core set of outcome domains and should be defined to improve neuropathic pain treatment and to achieve better comparability of clinical trials. Perspective: This systematic literature review assesses the use of patient reported outcome measures (PROMs) in chronic neuropathic pain. The results show that there is still a high heterogeneity, highlighting the need for a standardized core set of outcome domains and PROMs to improve comparability of clinical trials and neuropathic pain treatment.