Shedding light on neuropathic pain: Current and emerging tools for diagnosis, screening, and quantification

Ensuring the proper management of neuropathic pain is a contemporary challenge for professionals who care for patients with this type of pain. The estimated prevalence of neuropathic pain in Europe is 7%–8%. The objective of this study was to perform a non-systematic review on the diagnosis, screening, and quantification of neuropathic pain. For this purpose, a search was conducted of the PubMed/Medline, ScienceDirect, OVID, and SciELO databases for available evidence. The findings highlight the common occurrence of chronic neuropathic pain in clinical practice. However, diagnosing and managing this type of pain pose challenges due to its complexity and the individualized nature of cases. Precise diagnosis is crucial for effective management, involving therapeutic approaches that go beyond traditional pain treatments. It is noteworthy that until recent times, general questionnaires were utilized to assess neuropathic pain, lacking the ability to distinguish it from nociceptive pain or evaluate its broader impact on well-being. Biomarker pain panels hold promise in identifying treatable pain causes and evaluating treatment effectiveness. In conclusion, this review describes the diagnostic methods and tools for screening and quantifying neuropathic pain.

[1]  E. Stevens,et al.  Spontaneous activity in peripheral sensory nerves – a systematic review , 2023, bioRxiv.

[2]  Migyung Cho,et al.  Detection of brain regions responsible for chronic pain in osteoarthritis: an fMRI-based neuroimaging study using deep learning , 2023, Frontiers in Neurology.

[3]  K. Davis,et al.  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 , 2023, European journal of neurology.

[4]  D. Bouhassira,et al.  Personalized treatment of neuropathic pain: Where are we now? , 2023, European journal of pain.

[5]  Dayoung Kim,et al.  A Pilot Study of Autonomic Function Screening Tests for Differentiating Complex Regional Pain Syndrome Type II and Traumatic Neuropathic Pain , 2023, Medicina.

[6]  Zachary T. Olmsted,et al.  Review of the Treatments for Central Neuropathic Pain , 2022, Brain sciences.

[7]  D. Caraway,et al.  Biomarkers for Chronic Pain: Significance and Summary of Recent Advances , 2022, Pain research & management.

[8]  I. Raicher,et al.  Investigation of nerve fibers in the skin by biopsy: technical aspects, indications, and contribution to diagnosis of small-fiber neuropathy , 2022, Einstein.

[9]  Sara E. Berger,et al.  Assessing Pain Research: A Narrative Review of Emerging Pain Methods, Their Technosocial Implications, and Opportunities for Multidisciplinary Approaches , 2022, Frontiers in Pain Research.

[10]  K. N. Venugopala,et al.  Novel Therapies for the Treatment of Neuropathic Pain: Potential and Pitfalls , 2022, Journal of clinical medicine.

[11]  C. Woolf,et al.  Development of a PET radioligand for α2δ-1 subunit of calcium channels for imaging neuropathic pain , 2022, bioRxiv.

[12]  A. Curt,et al.  Cold evoked potentials elicited by rapid cooling of the skin in young and elderly healthy individuals , 2022, Scientific Reports.

[13]  M. Hubli,et al.  Improved acquisition of contact heat evoked potentials with increased heating ramp , 2022, Scientific reports.

[14]  K. Chakravarthy,et al.  How Well Do Current Laboratory Biomarkers Inform Clinical Decision-Making in Chronic Pain Management? , 2021, Journal of pain research.

[15]  Mark I. Johnson,et al.  The Identification of Blood Biomarkers of Chronic Neuropathic Pain by Comparative Transcriptomics , 2021, Neuromolecular medicine.

[16]  Jiabao Guo,et al.  Repetitive Transcranial Magnetic Stimulation for Neuropathic Pain on the Non-Motor Cortex: An Evidence Mapping of Systematic Reviews , 2021, Evidence-based complementary and alternative medicine : eCAM.

[17]  T. Deer,et al.  Cross-Validation of the Foundation Pain Index with PROMIS-29 in Chronic Pain Patients , 2021, Journal of pain research.

[18]  Joan Condell,et al.  Review of Wearable Devices and Data Collection Considerations for Connected Health , 2021, Sensors.

[19]  H. Yang,et al.  Diagnostic Performance of Three-Phase Bone Scintigraphy and Digital Infrared Thermography Imaging for Chronic Post-Traumatic Complex Regional Pain Syndrome , 2021, Diagnostics.

[20]  L. De Baets,et al.  Nociplastic Pain Criteria or Recognition of Central Sensitization? Pain Phenotyping in the Past, Present and Future , 2021, Journal of clinical medicine.

[21]  S. K. Kim,et al.  Neural Plasticity in the Brain during Neuropathic Pain , 2021, Biomedicines.

[22]  Valluvan Rangasamy,et al.  Cognition and Pain: A Review , 2021, Frontiers in Psychology.

[23]  Yeseul Kim,et al.  Investigation of serum biomarkers for neuropathic pain in neuromyelitis optica spectrum disorder: a preliminary study , 2021, Annals of Clinical Neurophysiology.

[24]  Boyi Liu,et al.  The NLRP3 inflammasome: an emerging therapeutic target for chronic pain , 2021, Journal of Neuroinflammation.

[25]  M. Invernizzi,et al.  Neuropathic Pain and Rehabilitation: A Systematic Review of International Guidelines , 2021, Diagnostics.

[26]  C. Cricelli,et al.  Not All Pain is Created Equal: Basic Definitions and Diagnostic Work-Up , 2020, Pain and Therapy.

[27]  S. Walker Neuropathic pain in children: Steps towards improved recognition and management , 2020, EBioMedicine.

[28]  Peter A. Smith K+ Channels in Primary Afferents and Their Role in Nerve Injury-Induced Pain , 2020, Frontiers in Cellular Neuroscience.

[29]  A. Rushton,et al.  Diagnostic utility of patient history, clinical examination and screening tool data to identify neuropathic pain in low back related leg pain: a systematic review and narrative synthesis , 2020, BMC Musculoskeletal Disorders.

[30]  A. Dahan,et al.  Neuropathic Pain: Challenges and Opportunities , 2020, Frontiers in Pain Research.

[31]  G. Fink,et al.  Diagnosis of peripheral neuropathy , 2020, Neurological Research and Practice.

[32]  T. Jensen,et al.  Neuropathic pain: From mechanisms to treatment. , 2020, Physiological reviews.

[33]  N. Aghaeepour,et al.  Discovery and validation of biomarkers to aid the development of safe and effective pain therapeutics: challenges and opportunities , 2020, Nature Reviews Neurology.

[34]  T. Schlereth Guideline “diagnosis and non interventional therapy of neuropathic pain” of the German Society of Neurology (deutsche Gesellschaft für Neurologie) , 2020, Neurological Research and Practice.

[35]  H. Flor,et al.  The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. , 2020, Pain.

[36]  R. Treede,et al.  Challenges of neuropathic pain: focus on diabetic neuropathy , 2020, Journal of Neural Transmission.

[37]  S. Kollias,et al.  Disentangling the Effects of Spinal Cord Injury and Related Neuropathic Pain on Supraspinal Neuroplasticity: A Systematic Review on Neuroimaging , 2020, Frontiers in Neurology.

[38]  M. Churyukanov,et al.  Central Neuropathic Pain and Profiles of Quantitative Electroencephalography in Multiple Sclerosis Patients , 2020, Frontiers in Neurology.

[39]  A. Curt,et al.  Contact Heat Evoked Potentials Are Responsive to Peripheral Sensitization: Requisite Stimulation Parameters , 2020, Frontiers in Human Neuroscience.

[40]  P. Tadi,et al.  Neuroanatomy, Trigeminal Reflexes , 2019 .

[41]  M. R. Begum VALIDITY AND RELIABILITY OF VISUAL ANALOGUE SCALE (VAS) FOR PAIN MEASUREMENT , 2019 .

[42]  Zhi Dou,et al.  The Application of Functional Magnetic Resonance Imaging in Neuropathic Pain , 2019, Medical Imaging - Principles and Applications [Working Title].

[43]  B. Gerdle,et al.  Psychometric properties of Short Form-36 Health Survey, EuroQol 5-dimensions, and Hospital Anxiety and Depression Scale in patients with chronic pain , 2019, Pain.

[44]  R. Treede,et al.  Can self-reported pain characteristics and bedside test be used for the assessment of pain mechanisms? An analysis of results of neuropathic pain questionnaires and quantitative sensory testing. , 2019, Pain.

[45]  A. Paladini,et al.  Quality of Life in Painful Peripheral Neuropathies: A Systematic Review , 2019, Pain research & management.

[46]  T. Schnitzer,et al.  Deconstructing biomarkers for chronic pain: context- and hypothesis-dependent biomarker types in relation to chronic pain. , 2019, Pain.

[47]  David L. Bennett,et al.  The Role of Voltage-Gated Sodium Channels in Pain Signaling. , 2019, Physiological reviews.

[48]  D. Levey,et al.  Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs , 2019, Molecular Psychiatry.

[49]  E. Mazzon,et al.  The neuropathic pain: An overview of the current treatment and future therapeutic approaches , 2019, International journal of immunopathology and pharmacology.

[50]  R. Ackerley,et al.  Microneurography as a tool to study the function of individual C-fiber afferents in humans: responses from nociceptors, thermoreceptors, and mechanoreceptors. , 2018, Journal of neurophysiology.

[51]  C. Cesarino,et al.  Correlation between neuropathic pain and quality of life , 2018 .

[52]  D. Kosson,et al.  Analysis of Anxiety, Depression and Aggression in Patients Attending Pain Clinics , 2018, International journal of environmental research and public health.

[53]  Åke Bernhard Vallbo,et al.  Microneurography: how it started and how it works. , 2018, Journal of neurophysiology.

[54]  A. Schnabel Acute neuropathic pain and the transition to chronic postsurgical pain. , 2018, Pain management.

[55]  M. Hurlé,et al.  MicroRNA-30c-5p modulates neuropathic pain in rodents , 2018, Science Translational Medicine.

[56]  M. Jensen,et al.  The utility and validity of pain intensity rating scales for use in developing countries , 2018, Pain reports.

[57]  H. Timmerman,et al.  The added value of bedside examination and screening QST to improve neuropathic pain identification in patients with chronic pain , 2018, Journal of pain research.

[58]  M. Bakhaidar,et al.  Neuroimaging of neuropathic pain: review of current status and future directions , 2018, Neurosurgical Review.

[59]  R. Baron,et al.  Diagnosis and assessment of neuropathic pain through questionnaires , 2018, The Lancet Neurology.

[60]  J. Villoria,et al.  Diagnostic accuracy of an identification tool for localized neuropathic pain based on the IASP criteria , 2018, Current medical research and opinion.

[61]  M. Debouverie,et al.  Quantitative and qualitative normative dataset for intraepidermal nerve fibers using skin biopsy , 2018, PloS one.

[62]  Theodore John Price,et al.  Translational Control Mechanisms in Persistent Pain , 2017, Trends in Neurosciences.

[63]  T. Jensen,et al.  AAPT Diagnostic Criteria for Central Neuropathic Pain. , 2017, The journal of pain : official journal of the American Pain Society.

[64]  J. Goeman,et al.  Investigating the validity of the DN4 in a consecutive population of patients with chronic pain , 2017, PloS one.

[65]  R. Fischer,et al.  Neuropathic Pain in Multiple Sclerosis – Current Therapeutic Intervention and Future Treatment Perspectives , 2017 .

[66]  D. Bansal,et al.  Hindi version of short form of douleur neuropathique 4 (S-DN4) questionnaire for assessment of neuropathic pain component: a cross-cultural validation study , 2017, The Korean journal of pain.

[67]  Seunghyeon Shin,et al.  Bone scintigraphy in patients with pain , 2017, The Korean journal of pain.

[68]  U. Abeyratne,et al.  A systematic review of the association between urinary biomarkers and pain , 2017 .

[69]  G. Moseley,et al.  Defensive reflexes in people with pain – a biomarker of the need to protect? A meta-analytical systematic review , 2017, Reviews in the neurosciences.

[70]  S. Williams,et al.  Distinguishing between nociceptive and neuropathic components in chronic low back pain using behavioural evaluation and sensory examination , 2017, Musculoskeletal science & practice.

[71]  E. Opsommer,et al.  Usefulness of laser-evoked potentials and quantitative sensory testing in the diagnosis of neuropathic spinal cord injury pain: a multiple case study , 2017, Spinal Cord.

[72]  J. Macdermid,et al.  Quantitative Sensory Testing in Chronic Musculoskeletal Pain. , 2016, Pain medicine.

[73]  R. Fillingim,et al.  Assessment of Chronic Pain: Domains, Methods, and Mechanisms. , 2016, The journal of pain : official journal of the American Pain Society.

[74]  Blair H. Smith,et al.  An Epidemiological Study of Neuropathic Pain Symptoms in Canadian Adults , 2016, Pain research & management.

[75]  Hasse Karlsson,et al.  Diagnosing Depression in Chronic Pain Patients: DSM-IV Major Depressive Disorder vs. Beck Depression Inventory (BDI) , 2016, PloS one.

[76]  P. Sandroni,et al.  Central Neuropathic Pain Syndromes. , 2016, Mayo Clinic proceedings.

[77]  R. Shankar,et al.  Depression and pain: the need for a new screening tool , 2016 .

[78]  R. Treede,et al.  Quantitative sensory testing (QST). English version , 2016, Der Schmerz.

[79]  D. Bouhassira,et al.  Validation of the Korean Version of the DN4 Diagnostic Questionnaire for Neuropathic Pain in Patients with Lumbar or Lumbar-Radicular Pain , 2016, Yonsei medical journal.

[80]  Blair H. Smith,et al.  Neuropathic pain: an updated grading system for research and clinical practice , 2016, Pain.

[81]  H. Bodur,et al.  Prevalence of Neuropathic Pain in Rheumatic Disorders: Association With Disease Activity, Functional Status and Quality of Life , 2015 .

[82]  R. Baron,et al.  Neuropathic pain: principles of diagnosis and treatment. , 2015, Mayo Clinic proceedings.

[83]  T. Jensen,et al.  Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms , 2014, The Lancet Neurology.

[84]  E. del Pozo,et al.  Diagnostic accuracy of two questionnaires for the detection of neuropathic pain in the Spanish population , 2014, European journal of pain.

[85]  Yu Kyeong Kim,et al.  Cortical and white matter alterations in patients with neuropathic pain after spinal cord injury , 2013, Brain Research.

[86]  A. Dahan,et al.  Corneal nerve quantification predicts the severity of symptoms in sarcoidosis patients with painful neuropathy , 2013 .

[87]  U. Baumgärtner,et al.  Pinprick-evoked brain potentials: a novel tool to assess central sensitization of nociceptive pathways in humans. , 2013, Journal of neurophysiology.

[88]  K. Davis,et al.  Sensorimotor and Pain Modulation Brain Abnormalities in Trigeminal Neuralgia: A Paroxysmal, Sensory-Triggered Neuropathic Pain , 2013, PloS one.

[89]  F. Reis,et al.  Quality of life and its domains in leprosy patients after neurolysis: a study using WHOQOL-BREF. , 2013, Leprosy review.

[90]  A. Dahan,et al.  ARA 290 Improves Symptoms in Patients with Sarcoidosis-Associated Small Nerve Fiber Loss and Increases Corneal Nerve Fiber Density , 2013, Molecular Medicine.

[91]  D. Collins,et al.  Assessing the risk of central post-stroke pain of thalamic origin by lesion mapping. , 2012, Brain : a journal of neurology.

[92]  F. Miller,et al.  Early phase drug development for treatment of chronic pain--options for clinical trial and program design. , 2012, Contemporary clinical trials.

[93]  R. Treede,et al.  International Spinal Cord Injury Pain Classification: part I. Background and description , 2011, Spinal Cord.

[94]  B. Laurent,et al.  The specific disease burden of neuropathic pain: Results of a French nationwide survey , 2011, PAIN.

[95]  C. Ramírez‐Maestre,et al.  S517 THE SPANISH VERSION OF THE PAIN ANXIETY SYMPTOMS SCALE (PASS-20): PRELIMINARY DATA ON ITS RELIABILITY, VALIDITY AND FACTORIAL STRUCTURE , 2011 .

[96]  A. Cámara,et al.  [Diagnosis and treatment of the neuropathic pain]. , 2009, Medicina clinica.

[97]  D. De Bacquer,et al.  Prevalence and impact on quality of life of peripheral neuropathy with or without neuropathic pain in type 1 and type 2 diabetic patients attending hospital outpatients clinics. , 2009, Diabetes & metabolism.

[98]  J. Ochoa,et al.  NEUROPATHIC PAIN: REDEFINITION AND A GRADING SYSTEM FOR CLINICAL AND RESEARCH PURPOSES , 2009, Neurology.

[99]  G. Cruccu,et al.  Tools for Assessing Neuropathic Pain , 2009, PLoS medicine.

[100]  S. Skevington,et al.  A measure for quality of life assessment in chronic pain: preliminary properties of the WHOQOL-pain , 2009, Journal of Behavioral Medicine.

[101]  T. Nurmikko,et al.  Development and preliminary validation of the NePIQoL: a quality-of-life measure for neuropathic pain. , 2009, Journal of pain and symptom management.

[102]  B. Laurent,et al.  Prevalence of chronic pain with neuropathic characteristics in the general population , 2008, PAIN.

[103]  J. Dostrovsky,et al.  Neuropathic pain , 2008, Neurology.

[104]  D. Bouhassira,et al.  Brain imaging of neuropathic pain , 2007, NeuroImage.

[105]  J. Rejas,et al.  Psychometric properties of the MOS (Medical Outcomes Study) Sleep Scale in patients with neuropathic pain , 2007, European journal of pain.

[106]  R. Baron,et al.  painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain , 2006, Current medical research and opinion.

[107]  R. Portenoy Development and testing of a neuropathic pain screening questionnaire: ID Pain , 2006, Current medical research and opinion.

[108]  R. Gálvez,et al.  Prevalencia del dolor neuroptico en Espaa: implicaciones clnicas, laborales y asistenciales , 2005 .

[109]  Blair H. Smith,et al.  The S-LANSS score for identifying pain of predominantly neuropathic origin: validation for use in clinical and postal research. , 2005, The journal of pain : official journal of the American Pain Society.

[110]  Bernard Laurent,et al.  Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4) , 2005, Pain.

[111]  Misha-Miroslav Backonja,et al.  Development of a Neuropathic Pain Questionnaire , 2003, The Clinical journal of pain.

[112]  Z. Bajwa,et al.  Diagnosis and treatment of neuropathic pain. , 2003, Journal of pain and symptom management.

[113]  M. Bennett,et al.  The LANSS Pain Scale: the Leeds assessment of neuropathic symptoms and signs , 2001, Pain.

[114]  M. Ashburn,et al.  Using the "TOPS," an outcomes instrument for multidisciplinary outpatient pain treatment. , 2000, Pain medicine.

[115]  Daniel J Buysse,et al.  The Pittsburgh sleep quality index: A new instrument for psychiatric practice and research , 1989, Psychiatry Research.

[116]  M. Bendersky,et al.  Fenotipos y diagnóstico en dolor neuropático , 2021 .

[117]  National Institute for Health and Care Excellence (NICE) , 2020, The Grants Register 2021.

[118]  M. C. Marthinussen,et al.  Acute Dental Pain and Salivary Biomarkers for Stress and Inflammation in Patients with Pulpal or Periapical Inflammation. , 2019, Journal of oral & facial pain and headache.

[119]  Shuu-Jiun Wang,et al.  Development and validation of a Taiwan version of the ID Pain questionnaire (ID Pain‐T) , 2018, Journal of the Chinese Medical Association : JCMA.

[120]  N. Attal,et al.  Neuropathic pain , 2017, Nature Reviews Disease Primers.

[121]  J. B. S. Garcia,et al.  Central neuropathic pain , 2016 .

[122]  F. Porto,et al.  Additional tests to investigate neuropathic pain. The value of electroneuromyography for neuropathic pain , 2016 .

[123]  I. Posso,et al.  Epidemiology of neuropathic pain , 2016 .

[124]  Y. Tao,et al.  Biomarkers for Chronic Neuropathic Pain and their Potential Application in Spinal Cord Stimulation: A Review. , 2016, Translational perioperative and pain medicine.

[125]  S. Ramamurthy Central Pain Syndrome , 2006 .

[126]  J. Rejas,et al.  [Prevalence of neuropathic pain in Spain: clinical, working and health care implications]. , 2005, Medicina clinica.

[127]  A. Elfering,et al.  Pain assessment , 2005, European Spine Journal.