The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study
Abstract
In neuropathic pain it has been suggested that pain phenotype based on putative pain mechanisms may predict response to treatment. This was a randomised, double-blind, placebo-controlled, and phenotype-stratified study with 2 6-week treatment periods of oxcarbazepine (1800-2400mg) and placebo. The primary efficacy measure was change in median pain intensity between baseline and the last week of treatment measured on an 11-point numeric rating scale, and the primary objective was to compare the effect of oxcarbazepine in patients with and without the irritable nociceptor phenotype as defined by hypersensitivity and preserved small nerve fibre function determined by detailed quantitative sensory testing. Ninety-seven patients with peripheral neuropathic pain due to polyneuropathy, surgical or traumatic nerve injury, or postherpetic neuralgia were randomised. The intention-to-treat population comprised 83 patients: 31 with the irritable and 52 with the nonirritable nociceptor phenotype. In the total sample, oxcarbazepine relieved pain of 0.7 points (on a numeric rating scale 0-10; 95% confidence interval [CI] 0.4-1.4) more than placebo (P=0.015) and there was a significant interaction between treatment and phenotype of 0.7 (95% CI 0.01-1.4, P=0.047). The number needed to treat to obtain one patient with more than 50% pain relief was 6.9 (95% CI 4.2-22) in the total sample, 3.9 (95% CI 2.3-12) in the irritable, and 13 (95% CI 5.3-∞) in the nonirritable nociceptor phenotype. In conclusion, oxcarbazepine is more efficacious for relief of peripheral neuropathic pain in patients with the irritable vs the nonirritable nociceptor phenotype.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Placebo response seems to have increased in recent neuropathic pain trials and may lead to underestimation of drug effects.
“One major issue is the placebo response which seems to have increased in recent trials of neuropathic pain and may lead to an underestimation of drug effects.51”
From Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis (2015) · cites this paper as [51]
Cites
Treede (2008) · doi:10.1212/01.wnl.0000282763.29778.59 · Cited by 2,746 · see citing works
Rolke, R., Baron, R., Maier, C., Tölle, T. R., Treede, R., Beyer, A., Binder, A., Birbaumer, N., Birklein, F., Bötefür, I. C., et al. (2006) · Pain · doi:10.1016/j.pain.2006.01.041 · Cited by 2,606 · see citing works
Self-citationNeuropathic pain: aetiology, symptoms, mechanisms, and management
Woolf, C. J., & Mannion, R. (1999) · The Lancet · doi:10.1016/s0140-6736(99)01307-0 · Cited by 2,231 · see citing works
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 · see citing works
EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision
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 · Cited by 1,873 · see citing works
Self-citationThe association of sleep and pain: an update and a path forward
Finan, P. H., Goodin, B. R., & Smith, M. T. (2013) · The Journal of Pain · doi:10.1016/j.jpain.2013.08.007 · Cited by 1,620 · see citing works
Development and validation of the Neuropathic Pain Symptom Inventory
Bouhassira, D., Attal, N., Fermanian, J., Alchaar, H., Gautron, M., Masquelier, E., Rostaing, S., Lanteri-Minet, M., Collin, E., Grisart, J., et al. (2004) · Pain · doi:10.1016/j.pain.2003.12.024 · Cited by 1,329 · see citing works
The evidence for pharmacological treatment of neuropathic pain
Finnerup, N. B., Sindrup, S. H., & Jensen, T. S. (2010) · Pain · doi:10.1016/j.pain.2010.06.019 · Cited by 1,045 · see citing works
Self-citationMaier, C., Baron, R., Tölle, T. R., Binder, A., Birbaumer, N., Birklein, F., Gierthmühlen, J., Flor, H., Geber, C., Huge, V., et al. (2010) · Pain · doi:10.1016/j.pain.2010.05.002 · Cited by 1,021 · see citing works
Self-citationDeconstructing the Neuropathic Pain Phenotype to Reveal Neural Mechanisms
von Hehn, C. A., Baron, R., & Woolf, C. J. (2012) · Neuron · doi:10.1016/j.neuron.2012.02.008 · Cited by 804 · see citing works
Sodium Channels in Normal and Pathological Pain
Dib‐Hajj, S. D., Cummins, T., Black, J. A., & Waxman, S. G. (2010) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-060909-153234 · Cited by 607 · see citing works
Magerl, W., Krumova, E. K., Baron, R., Tölle, T. R., Treede, R., & Maier, C. (2010) · Pain · doi:10.1016/j.pain.2010.07.026 · Cited by 604 · see citing works
Self-citationPostherpetic Neuralgia: Irritable Nociceptors and Deafferentation
Fields, H. L., Rowbotham, M. C., & Baron, R. (1998) · Neurobiology of Disease · doi:10.1006/nbdi.1998.0204 · Cited by 560 · see citing works
Sodium Channels and Mechanisms of Neuropathic Pain
Devor, M. G. (2006) · Journal of Pain · doi:10.1016/j.jpain.2005.09.006 · Cited by 401 · see citing works
Lamotrigine for central poststroke pain
Vestergaard, K., Andersen, G., Gottrup, H., Kristensen, B. T., & Jensen, T. S. (2001) · Neurology · doi:10.1212/wnl.56.2.184 · Cited by 324 · see citing works
Self-citationIntravenous lidocaine in central pain
Attal, N., Gaudé, V., Brasseur, L., Dupuy, M., Guirimand, F., Parker, F., & Bouhassira, D. (2000) · Neurology · doi:10.1212/wnl.54.3.564 · Cited by 293 · see citing works
Baron, R., Förster, M., & Binder, A. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70189-8 · Cited by 262 · see citing works
Combination pharmacotherapy for management of chronic pain: from bench to bedside
Gilron, I., Jensen, T. S., & Dickenson, A. H. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70193-5 · Cited by 241 · see citing works
Self-citationReappraising neuropathic pain in humans—how symptoms help disclose mechanisms
Truini, A., Garcı́a-Larrea, L., & Cruccu, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.180 · Cited by 224 · see citing works
The Topiramate Diabetic Neuropathic Pain Study Group*, Thienel, U., Neto, W., Schwabe, S., & Vijapurkar, U. (2004) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.2004.00338.x · Cited by 188 · see citing works
Oxcarbazepine in painful diabetic neuropathy: a randomized, placebo‐controlled study
Dogra, S., Beydoun, S. R., Mazzola, J. L., Hopwood, M. B., & Wan, Y. (2004) · European Journal of Pain · doi:10.1016/j.ejpain.2004.11.006 · Cited by 178 · see citing works
Duloxetine use in chronic painful conditions – individual patient data responder analysis
Moore, A., Cai, N., Skljarevski, V., & Tölle, T. R. (2013) · European Journal of Pain · doi:10.1002/j.1532-2149.2013.00341.x · Cited by 169 · see citing works
Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy
Campbell, C. M., Kipnes, M. S., Stouch, B. C., Brady, K. L., Kelly, M., Schmidt, W. K., Petersen, K. L., Rowbotham, M. C., & Campbell, J. N. (2012) · Pain · doi:10.1016/j.pain.2012.04.014 · Cited by 165 · see citing works
Vinik, A. I., Tuchman, M. M., Safirstein, B., Corder, C. N., Kirby, L. C., Wilks, K. L., Quessy, S. N., Blum, D., Grainger, J., White, J., et al. (2006) · Pain · doi:10.1016/j.pain.2006.09.040 · Cited by 163 · see citing works
Postherpetic neuralgia: Topical lidocaine is effective in nociceptor–deprived skin
Wasner, G. L., Kleinert, A., Binder, A., Schattschneider, J., & Baron, R. (2005) · Journal of Neurology · doi:10.1007/s00415-005-0717-z · Cited by 154 · see citing works
Oxcarbazepine: Mechanisms of Action
McLean, M. J., Schmutz, M., Wamil, A. W., et al. (1994) · Epilepsia · doi:10.1111/j.1528-1157.1994.tb05949.x · Cited by 144 · see citing works
Lacosamide in Painful Diabetic Neuropathy: An 18-Week Double-Blind Placebo-Controlled Trial
Shaibani, A. I., Fares, S., Sélam, J.-L., Arslanian, A., Simpson, J. N., Sen, D. L., & Bongardt, S. (2009) · Journal of Pain · doi:10.1016/j.jpain.2009.01.322 · Cited by 132 · see citing works
Stefani, A., Pisani, A., Murtas, M. D., Mercuri, N. B., Marciani, M. G., & Calabresi, P. (1995) · Epilepsia · doi:10.1111/j.1528-1157.1995.tb00958.x · Cited by 111 · see citing works
A randomized, placebo-controlled study of oxcarbazepine in painful diabetic neuropathy
Großkopf, J., Mazzola, J., Wan, Y., & Hopwood, M. B. (2006) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.2005.00559.x · Cited by 94 · see citing works
Oxcarbazepine in painful diabetic neuropathy: results of a dose-ranging study
Beydoun, A. A., Shaibani, A. I., Hopwood, M. B., & Wan, Y. (2006) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.2006.00631.x · Cited by 92 · see citing works
Towards physiologically based treatment of patients with neuropathic pain
Max, M. B. (1990) · Pain · doi:10.1016/0304-3959(90)91156-d · Cited by 74 · see citing works
Bischoff, J. M., Petersen, M., Üçeyler, N., Sommer, C., Kehlet, H., & Werner, M. U. (2013) · Anesthesiology · doi:10.1097/aln.0b013e3182a2a243 · Cited by 53 · see citing works
Inhibitory effect of oxcarbazepine on high-frequency firing in peripheral nerve fibers
Ichikawa, K., Koyama, N., Kiguchi, S., et al. (2001) · European Journal of Pharmacology · doi:10.1016/s0014-2999(01)01007-x · Cited by 42 · see citing works
Role of Small-Fiber Afferents in Pain Mechanisms With Implications on Diagnosis and Treatment
Albrecht, P. J., & Rice, F. L. (2010) · Current Pain and Headache Reports · doi:10.1007/s11916-010-0105-y · Cited by 25 · see citing works
Are sodium channel blockers useless in peripheral neuropathic pain?
Sindrup, S. H., & Jensen, T. S. (2006) · Pain · doi:10.1016/j.pain.2006.09.010 · Cited by 24 · see citing works
Self-citationDifferential 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 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis
Finnerup, N. B., Attal, N., Haroutounian, S., McNicol, E., Baron, R., Dworkin, R. H., Gilron, I., Haanpää, M., Hansson, P., Jensen, T. S., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70251-0 · Cited by 3,980 · see citing works
Self-citationNew Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain
Feldman, E. L., Nave, K.-A., Jensen, T. S., & Bennett, D. L. H. (2017) · Neuron · doi:10.1016/j.neuron.2017.02.005 · Cited by 915 · see citing works
Self-citationDiabetic Peripheral Neuropathy: Epidemiology, Diagnosis, and Pharmacotherapy
Iqbal, Z., Azmi, S., Yadav, R., Ferdousi, M., Kumar, M., Cuthbertson, D. J., Lim, J., Malik, R. A., & Alam, U. (2018) · Clinical Therapeutics · doi:10.1016/j.clinthera.2018.04.001 · Cited by 487 · see citing works
Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations
Edwards, R. R., Dworkin, R. H., Turk, D. C., Angst, M. S., Dionne, R., Freeman, R., Hansson, P., Haroutounian, S., Arendt-Nielsen, L., Attal, N., et al. (2016) · Pain · doi:10.1097/j.pain.0000000000000602 · Cited by 403 · see citing works
Jensen, T. S., Karlsson, P., Gylfadottir, S. S., Andersen, S. T., Bennett, D. L., Tankisi, H., Finnerup, N. B., Terkelsen, A. J., Khan, K., Themistocleous, A. C., et al. (2021) · Brain · doi:10.1093/brain/awab079 · Cited by 265 · see citing works
Self-citationNonnarcotic Methods of Pain Management
Finnerup, N. B. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1807061 · Cited by 153 · see citing works
Self-citationPetersen, K. K., Vaegter, H. B., Stubhaug, A., Wolff, A., Scammell, B. E., Arendt-Nielsen, L., & Larsen, D. B. (2021) · Pain · doi:10.1097/j.pain.0000000000002019 · Cited by 140 · see citing works
Ketamine for refractory chronic pain: a 1-year follow-up study
Corriger, A., Voute, M., Lambert, C., Pereira, B., & Pickering, G. (2022) · Pain · doi:10.1097/j.pain.0000000000002403 · Cited by 31 · see citing works
- Authors
- Demant, D. T., Lund, K., Vollert, J., Maier, C., Segerdahl, M., Finnerup, N. B., Jensen, T. S., & Sindrup, S. H.
- Affiliations
- Odense University Hospital (DK)
- Aarhus University Hospital (DK)
- BG University Hospital Bergmannsheil Bochum (DE)
- Lundbeck (Denmark) (DK)
- Venue
- Pain
- Published
- 2014-11
- Volume
- 155
- Issue
- 11
- Pages
- 2263-2273
- ISSN
- 0304-3959 (ISSN-L)
- OpenAlex
- W2041635174
- Cited by
- 440
- References
- 36
- Citations by year
- 2026: 18 · 2025: 14 · 2024: 20 · 2023: 28 · 2022: 38 · 2021: 51 · 2020: 59 · 2019: 40 · 2018: 49 · 2017: 42 · 2016: 46 · 2015: 28 · 2014: 3 · 2013: 1
- FWCI
- 26.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Funders
- Pfizer
- Astellas Pharma
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Keywords
- oxcarbazepine, peripheral neuropathic pain, pain phenotypes, quantitative sensory testing, postherpetic neuralgia, traumatic nerve injury, surgical nerve injury, polyneuropathy, treatment response prediction, pain intensity
- MeSH terms
- Oxcarbazepine, Adult, Aged, Aged, 80 and over, Carbamazepine, Double-Blind Method, Female, Humans, Male, Middle Aged, Pain, Pain Measurement, Peripheral Nervous System Diseases, Treatment Outcome, Cross-Over Studies, Young Adult, Voltage-Gated Sodium Channel Blockers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
