Cited by 1,873Pain Mechanisms and TreatmentsPain Management and TreatmentPain Management and Opioid Use

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EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision

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Attal, N., Cruccu, G., Baron, R., Haanpää, M., Hansson, P., Jensen, T. S., Nurmikko, T.·2010·European Journal of Neurology

DOI 10.1111/j.1468-1331.2010.02999.x

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Abstract

BACKGROUND AND OBJECTIVES: This second European Federation of Neurological Societies Task Force aimed at updating the existing evidence about the pharmacological treatment of neuropathic pain since 2005. METHODS: Studies were identified using the Cochrane Database and Medline. Trials were classified according to the aetiological condition. All class I and II randomized controlled trials (RCTs) were assessed; lower class studies were considered only in conditions that had no top-level studies. Treatments administered using repeated or single administrations were considered, provided they are feasible in an outpatient setting. RESULTS: Most large RCTs included patients with diabetic polyneuropathies and post-herpetic neuralgia, while an increasing number of smaller studies explored other conditions. Drugs generally have similar efficacy in various conditions, except in trigeminal neuralgia, chronic radiculopathy and HIV neuropathy, with level A evidence in support of tricyclic antidepressants (TCA), pregabalin, gabapentin, tramadol and opioids (in various conditions), duloxetine, venlafaxine, topical lidocaine and capsaicin patches (in restricted conditions). Combination therapy appears useful for TCA-gabapentin and gabapentin-opioids (level A). CONCLUSIONS: There are still too few large-scale comparative studies. For future trials, we recommend to assess comorbidities, quality of life, symptoms and signs with standardized tools and attempt to better define responder profiles to specific drug treatments.

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Anticonvulsant drugs for acute and chronic pain
Wiffen, P. J., Collins, S., McQuay, H. J., Carroll, D., Jadad, A. R., & Moore, R. A. (2005) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd001133.pub2 · Cited by 409
Retracted
Gabapentin for acute and chronic pain
Wiffen, P. J., McQuay, H. J., Edwards, J. E., & Moore, R. A. (2005) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005452 · Cited by 247
Retracted
Gabapentin for acute and chronic pain
Wiffen, P. J., McQuay, H. J., Edwards, J. E., & Moore, R. A. (2011) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005452.pub2 · Cited by 230
Retracted
Topical lidocaine for the treatment of postherpetic neuralgia
Khaliq, W., Alam, S., & Puri, N. K. (2007) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004846.pub2 · Cited by 160
Retracted
Anticonvulsant drugs for acute and chronic pain
Wiffen, P. J., Collins, S., McQuay, H. J., Carroll, D., Jadad, A. R., & Moore, R. A. (2010) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd001133.pub3 · Cited by 153
Retracted
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Self-citation
Pharmacologic management of neuropathic pain: Evidence-based recommendations
Dworkin, R. H., O’Connor, A. B., Backonja, M., Farrar, J. T., Finnerup, N. B., Jensen, T. S., Kalso, E. A., Loeser, J. D., Miaskowski, C., Nurmikko, T. J., et al. (2007) · Pain · doi:10.1016/j.pain.2007.08.033 · Cited by 2,126

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Rollason, V., Lloret‐Linares, C., Lorenzini, K. I., Daali, Y., Gex‐Fabry, M., Piguet, V., Besson, M. J., Samer, C. F., & Desmeules, J. A. (2020) · Journal of Personalized Medicine · doi:10.3390/jpm10040198 · Cited by 16
Enhancement of antinociceptive effect of morphine by antidepressants in diabetic neuropathic pain model
Cegielska-Perun, K., Bujalska‐Zadrożny, M., Gąsińska, E., & Makulska-Nowak, H. E. (2014) · Pharmacological Reports · doi:10.1016/j.pharep.2013.09.003 · Cited by 16
Local Administration of Methylcobalamin and Lidocaine for Acute Ophthalmic Herpetic Neuralgia: A Single‐Center Randomized Controlled Trial
Xú, G., Xu, S., Cheng, C., Xu, G., Tang, W., & Xu, J. (2015) · Pain Practice · doi:10.1111/papr.12328 · Cited by 16
“The primary objective of the trial was to explore whether local MeB12 in combination with lidocaine injection administered in the early stages of the onset of HZO could reduce the intensity and duration of AOHN and whether it had the potential to prevent or reduce the incidence and/or severity of PHN.”
BackgroundInfluential
Treatment of Diabetic Cardiovascular Autonomic, Peripheral and Painful Neuropathy. Focus on the Treatment of Cardiovascular Autonomic Neuropathy with ACE Inhibitors
Didangelos, T., & Veves, A. (2019) · Current Vascular Pharmacology · doi:10.2174/1570161117666190521101342 · Cited by 17
High-Dose Intravenous Immunoglobulin Is Effective in Painful Diabetic Polyneuropathy Resistant to Conventional Treatments. Results of a Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial
Jann, S., Fazio, R., Cocito, D., Toscano, A., Schenone, A. E., Marfia, G. A., Antonini, G., Franceschini, L. D. T., Mazzeo, A. T., Grandis, M., et al. (2019) · Pain Medicine · doi:10.1093/pm/pnz331 · Cited by 16
Gender Differences in Medication Adverse Effects Experienced by People Living With Chronic Pain
Nguefack, H. L. N., Pagé, M. G., Guénette, L., Blais, L., Diallo, M., Godbout-Parent, M., Fonseca, A. A., & Lacasse, A. (2022) · Frontiers in Pain Research · doi:10.3389/fpain.2022.830153 · Cited by 19
Ion channels in cancer-induced bone pain: from molecular mechanisms to clinical applications
Lu, H.-J., Wu, X., & Wei, Q.-Q. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1239599 · Cited by 15
“Capsaicin is widely used in the treatment of neuropathic, osteoarthritic, and musculoskeletal pain, and suppresses osteoclast formation, inflammatory bone resorption, and cyclooxygenase-2 (COX-2) expression; however, no clinical trials examining the potential role of capsaicin and its synthetic isomers or precursors i…”
Background
Neuropathic pain in burn patients – A common problem with little literature: A systematic review
Stanton, E. W., Won, P., Manasyan, A., Gurram, S., Gilllenwater, T. J., & Yenikomshian, H. A. (2024) · Burns · doi:10.1016/j.burns.2024.02.013 · Cited by 15
Modification of morphine analgesia by venlafaxine in diabetic neuropathic pain model
Cegielska-Perun, K., Bujalska‐Zadrożny, M., & Makulska-Nowak, H. E. (2012) · Pharmacological Reports · doi:10.1016/s1734-1140(12)70923-4 · Cited by 15
Examining the Time to Therapeutic Effect of Pregabalin in Spinal Cord Injury Patients With Neuropathic Pain
Cardenas, D. D., Emir, B., & Parsons, B. (2015) · Clinical Therapeutics · doi:10.1016/j.clinthera.2015.02.028 · Cited by 15
Drugs for the treatment of peripheral neuropathies
Marmiroli, P., & Cavaletti, G. (2015) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2016.1120719 · Cited by 15
“considered as as second- and third-line treatments, respectively.[71] A systematic review and meta-analysis of pharmacological therapies for painful diabetic peripheral neuropathy including nearly 12,000 treated”
Background
The role of tramadol in pain management in Latin America: a report by the Change Pain Latin America Advisory Panel
Garcia, J. B. S., Lech, O., Kraychete, D. C., Rico, M. A., Castro, J. J. H., Colimon, F., Guerrero, C., Gallegos, M. S., Lara-Solares, A., Cantisani, J. A. F., et al. (2017) · Current Medical Research and Opinion · doi:10.1080/03007995.2017.1354821 · Cited by 15
“in neuropathic pain [34], acute and chronic low back pain [35], and osteoarthritis pain [36].”
Background
Terapias emergentes en desarrollo clínico y nuevas aportaciones en dolor neuropático
Montero, A. A., Carnerero, C. I. S., & Goicoechea, C. (2019) · Revista Española de Anestesiología y Reanimación · doi:10.1016/j.redar.2019.02.003 · Cited by 15
Neuropathic Pain and Burning Mouth Syndrome
Dym, H., Lin, S., & Thakkar, J. (2020) · Dental Clinics of North America · doi:10.1016/j.cden.2019.12.009 · Cited by 15
US FDA-Validated Green GC–MS Method for Analysis of Gabapentin, Tramadol and/or Amitriptyline Mixtures in Biological Fluids
Naguib, I. A., Ali, N. A., Elroby, F. A., Ghobashy, M. R. E., & Abdallah, F. F. (2020) · Bioanalysis · doi:10.4155/bio-2020-0217 · Cited by 15
Comparative Assessment of the Activity of Racemic and Dextrorotatory Forms of Thioctic (Alpha-Lipoic) Acid in Low Back Pain: Preclinical Results and Clinical Evidences From an Open Randomized Trial
Pacini, A., Tomassoni, D., Trallori, E., Micheli, L., Amenta, F., Ghelardini, C., Mannelli, L. D. C., & Traini, E. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.607572 · Cited by 15
“The guidelines of the European Federation of Neurological Societies (EFNS) and of the International Association for the Study of Pain (IASP) have been considering the use of different classes of drugs, such as analgesics, antidepressants and anticonvulsants, for the treatment of neuropathic pain (Dworkin et al., 2007;…”
Chronic Nerve Injuries and Delays in Surgical Treatment Negatively Impact Patient-reported Quality of Life
Felder, J. M., & Ducic, I. (2021) · Plastic & Reconstructive Surgery Global Open · doi:10.1097/gox.0000000000003570 · Cited by 15
Health care utilization and expenditures among Medicaid beneficiaries with neuropathic pain following spinal cord injury
Margolis, J. M., Juneau, P. L., Sadosky, A., Cappelleri, J. C., Bryce, T. N., & Nieshoff, E. C. (2014) · Journal of Pain Research · doi:10.2147/jpr.s63796 · Cited by 15
Tramadol/Paracetamol Fixed-Dose Combination for Chronic Pain Management in Family Practice: A Clinical Review
Merchante, I. M., Pergolizzi, J. V., van de Laar, M. A. F. J., Mellinghoff, H.-U., Nalamachu, S. R., O’Brien, J., Perrot, S., & Raffa, R. B. (2013) · ISRN Family Medicine · doi:10.5402/2013/638469 · Cited by 15
Intrathecal injection of phosphodiesterase 4B-specific siRNA attenuates neuropathic pain in rats with L5 spinal nerve ligation
Ji, Q., Yan, D., He, X., Liu, Q., Liu, J., Li, W., & Zhang, L. (2015) · Molecular Medicine Reports · doi:10.3892/mmr.2015.4713 · Cited by 15
“At present, pain relief can only be achieved in 40-60% of patients; therefore, it is important to study the underlying mechanisms of pain, with the aim of eventually developing novel therapeutic drugs (2).”
Pharmacologic Treatment of Neuropathic Pain Following Spinal Cord Injury
DeFrates, S. R., & Cook, A. M. (2011) · Orthopedics · doi:10.3928/01477447-20110124-19 · Cited by 15
Predictive value of a diagnostic block in focal nerve injury with neuropathic pain when surgery is considered
Malessy, M. J. A., de Boer, R., Muñoz–Romero, I., Eekhof, J. L. A., van Zwet, E. W., Kliot, M., Dahan, A., & Pondaag, W. (2018) · PLoS ONE · doi:10.1371/journal.pone.0203345 · Cited by 17
“So far, most trials on neurostimulation for pain relief did not comply with the requirements of evidence-based medicine.[5] Surgical treatment of the damaged nerve is considered as an option when all other treatments have failed.”
Background
Pharmacotherapeutic Management of Neuropathic Pain in End-Stage Renal Disease
Raouf, M., Bettinger, J. J., Wegrzyn, E., Mathew, R. O., & Fudin, J. (2020) · Kidney Diseases · doi:10.1159/000504299 · Cited by 15
Pathophysiological Mechanisms of Neuropathic Pain
Leone, C. M., Biasiotta, A., Cesa, S. L., Stefano, G. D., Cruccu, G., & Truini, A. (2011) · Future Neurology · doi:10.2217/fnl.11.23 · Cited by 15
Self-citation
Diagnostik und Therapie neuropathischer Schmerzen
Goßrau, G., & Sabatowski, R. (2021) · Der Anaesthesist · doi:10.1007/s00101-021-01039-x · Cited by 15
Pain Management at the End of Life in the Emergency Department: A Narrative Review of the Literature and a Practical Clinical Approach
Serra, S., Spampinato, M. D., Riccardi, A., Guarino, M., Fabbri, A., Orsi, L., & Iaco, F. D. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12134357 · Cited by 14
“However, numerous authors have criticised this approach for the following reasons: (i) Some adjuvants are first-line therapies for certain types of pain, such as neuropathic pain [87]; (ii) Weak opioids have been shown to be of little use in the treatment of pain [88]; (iii) The presence of NSAIDs proposed for tier I…”
Background
PATTERNS OF PRESCRIPTION AND ADR MONITORING OF DRUGS IN THE MANAGEMENT OF NEUROPATHIC PAIN IN A TERTIARY CARE TEACHING HOSPITAL
Jena, S. S., Jena, M., Patro, N., Mishra, S. D., Panda, M., & Dash, M. (2021) · International Journal of Pharmacy and Pharmaceutical Sciences · doi:10.22159/ijpps.2021v13i3.41308 · Cited by 14
“%) which is in contrast to a study showing secondary amine tricyclic antidepressants (Nortriptyline and Desipramine) are better tolerated than tertiary amine tricyclic antidepressants (Amitriptyline, Imipramine, Clomipramine) so more prescribed [27].”
BackgroundInfluential
Prescription Patterns of Pain Medicine Physicians
Benzon, H. T., Kendall, M. C., Katz, J. A., Benzon, H. A., Malik, K., Cox, P., Dean, K., & Avram, M. J. (2012) · Pain Practice · doi:10.1111/papr.12011 · Cited by 14
Effectiveness of Pregabalin as Monotherapy or Combination Therapy for Neuropathic Pain in Patients Unresponsive to Previous Treatments in a Spanish Primary Care Setting
Tarrío, E. B., Mateos, R. G., Zamorano, E., Gómez, V. L., & Páramo, M. P. (2013) · Clinical Drug Investigation · doi:10.1007/s40261-013-0116-7 · Cited by 14
Improvement in pain severity category in clinical trials of pregabalin
Parsons, B., Argoff, C., Clair, A. G., & Emir, B. (2016) · Journal of Pain Research · doi:10.2147/jpr.s102696 · Cited by 14
“This was, perhaps, unexpected given the optimal approach is typically to carefully titrate pregabalin to the highest tolerable dose, 37-39 which in this analysis would be more closely represented by the flexible dosing group.”
Recommandations pour le diagnostic et la prise en charge de la névralgie trigéminale classique
Donnet, A., Simon, É., Cuny, E., Demarquay, G., Ducros, A., de Gaalon, S., Giraud, P., Guegan-Massardier, E., Lantéri‐Minet, M., Leclercq, D., et al. (2018) · Neurochirurgie · doi:10.1016/j.neuchi.2018.04.001 · Cited by 14
Headache in the Older Population: Causes, Diagnoses, and Treatments
Robblee, J. V., & Singh, R. B. H. (2020) · Current Pain and Headache Reports · doi:10.1007/s11916-020-00866-8 · Cited by 14
Characterization of Mechanical Allodynia and Skin Innervation in a Mouse Model of Type-2 Diabetes Induced by Cafeteria-Style Diet and Low-Doses of Streptozotocin
Castañeda‐Corral, G., Velázquez-Salazar, N. B., Martínez-Martínez, A., Taboada-Serrano, J. N., Núñez-Aragón, P. N., González-Palomares, L., Acosta‐González, R. I., Petricevich, V. L., Acevedo‐Fernández, J. J., Montes, S., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.628438 · Cited by 14
“These findings agree with clinical observations as these drugs have been included in the guidelines by the American Diabetes Association and European Federation of Neurological Societies Task Force to treat painful neuropathy in diabetic patients (Attal et al., 2010; Pop-Busui et al., 2017; Iqbal et al., 2018).”
Result
Expert consensus of the Chinese Association for the Study of Pain on ion channel drugs for neuropathic pain
Xiao, H., Ma, K., Huang, D., Liu, X., Liu, T., Liu, Q., Liu, G., Song, T., Tao, W., Wu, D., et al. (2021) · World Journal of Clinical Cases · doi:10.12998/wjcc.v9.i9.2100 · Cited by 14
Antiallodynic action of phosphodiesterase inhibitors in a mouse model of peripheral nerve injury
Megat, S., Hugel, S., Journée, S. H., Bohren, Y., Lacaud, A., Lelièvre, V., Doridot, S., Villa, P., Bourguignon, J., Salvat, É., et al. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108909 · Cited by 14
Effectiveness and Tolerability of Dronabinol Use in Patients with Chronic Pain: A Retrospective Analysis of 12-Week Open-Label Real-World Data Provided by the German Pain e-Registry
Ueberall, M. A., Horlemann, J., Schürmann, N., Kalaba, M., & Ware, M. A. (2022) · Pain Medicine · doi:10.1093/pm/pnac010 · Cited by 14
Effect of CT-Guided Gasserian Ganglion Block with Local Anesthetics and Steroids on Acute/Subacute Zoster-Related Trigeminal Neuralgia: A Multicenter Retrospective Study
Sun, Z., Liu, L., Liu, H., & Luo, F. (2022) · Journal of Pain Research · doi:10.2147/jpr.s375257 · Cited by 14
“3% of HZ patients.(7) Acute zoster-related trigeminal neuralgia presents as facial pain within 30 days of zoster onset, characterized by severe burning pain and tingling in the skin of the innervated area, along with the occasional tearing or stabbing pain.”
Background
Differential Effects of a 5% lidocaine medicated patch in peripheral nerve injury
Madsen, C. S., Johnsen, B., Fuglsang‐Frederiksen, A., Jensen, T. S., & Finnerup, N. B. (2013) · Muscle & Nerve · doi:10.1002/mus.23794 · Cited by 14
Self-citation

Authors: Attal, N., Cruccu, G., Baron, R., Haanpää, M., Hansson, P., Jensen, T. S., & Nurmikko, T.
Affiliations: Inserm (FR)
Sapienza University of Rome (IT)
University Hospital Schleswig-Holstein (DE)
Helsinki University Hospital (FI)
Karolinska University Hospital (SE)
Aarhus University Hospital (DK)
University of Liverpool (GB)
Corresponding author: Attal, N.
ORCID: Attal, N.
Cruccu, G.
Baron, R.
Haanpää, M.
Hansson, P.
Jensen, T. S.
Nurmikko, T.
Venue: European Journal of Neurology
Publisher: Wiley
Published: 2010-04-07
Volume: 17
Issue: 9
Pages: 1113
ISSN: 1351-5101 (ISSN-L)
1468-1331
DOI: 10.1111/j.1468-1331.2010.02999.x
OpenAlex: W2128412489
Cited by: 1,873
References: 236
Citations by year: 2026: 39 · 2025: 59 · 2024: 85 · 2023: 81 · 2022: 91 · 2021: 128 · 2020: 134 · 2019: 112 · 2018: 102 · 2017: 151 · 2016: 136 · 2015: 152 · 2014: 185 · 2013: 185 · 2012: 121
FWCI: 89.44
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: European Journal of Neurology (publishedVersion)
PubMed (publishedVersion)
IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
Keywords: neuropathic pain, pharmacotherapy, diabetic polyneuropathy, postherpetic neuralgia, trigeminal neuralgia, chronic radiculopathy, HIV neuropathy, tricyclic antidepressants, pregabalin, gabapentin, tramadol, opioids, duloxetine, venlafaxine, topical lidocaine, capsaicin patch, combination therapy, treatment efficacy
MeSH terms: Gabapentin, Amines, Analgesia, Analgesics, Analgesics, Opioid, Antidepressive Agents, Tricyclic, Cyclohexanecarboxylic Acids, Drug Therapy, Combination, Europe, gamma-Aminobutyric Acid, Humans, Neuralgia, Peripheral Nervous System Diseases, Randomized Controlled Trials as Topic, Treatment Outcome, Outcome Assessment, Health Care

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EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision

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