Mechanismenbasierte Therapie neuropathischer Schmerzen

ZUSAMMENFASSUNG

Neuropathische Schmerzen entstehen als direkte Folge einer Erkrankung oder Läsion des somatosensorischen Systems. In der Allgemeinbevölkerung haben sie eine Prävalenz von bis zu 10 %, bei Diabetikern bis zu 30 %. Typisch ist das gleichzeitige Auftreten von Plus- (Schmerz, Hyperalgesie) und Minussymptomen (Hypästhesie, Hypoalgesie) für thermische und/oder mechanische Reize, wobei unterschiedliche Symptomkonstellationen unabhängig von der Krankheitsätiologie auftreten. Die genaue Analyse der sensorischen Symptome erlaubt Rückschlüsse über die Mechanismen der Schmerzentstehung (z. B. periphere und zentrale Sensibilisierung, Störung endogener Schmerzhemmung), was zusammen mit der Kenntnis der pharmakologischen Angriffspunkte der üblicherweise eingesetzten Medikamente (Antikonvulsiva, Antidepressiva, Opioide und topisch applizierte Wirkstoffe) eine gezieltere Pharmakotherapie ermöglicht. Einige Studien konnten einen Zusammenhang zwischen dem sensorischen Profil und dem Therapieeffekt verschiedener Medikamente nachweisen. Weitere Studien sind notwendig, um diesbezüglich leitlinienrelevante Empfehlungen für die individuelle Therapieauswahl auszusprechen.

• Literatur

• 1 Attal N, de Andrade DC, Adam F. et al Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, doubleblind, placebo-controlled trial.. Lancet Neurol 2016; 15: 555-565 doi: 10.1016/S1474-4422(16)00017-X
• 2 Backonja MM, Attal N, Baron BouhassiraR. et al Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus.. Pain 2013; 154: 1807-1819 doi: 10.1016/j.pain.2013.05.047
• 3 Baron R, Maier C, Attal N. et al Peripheral neuropathic pain: A mechanism-related organizing principle based on sensory profiles.. Pain 2017; 158: 261-272 doi: 10.1097/j.pain.0000000000000753
• 4 Blankenburg M, Boekens H, Hechler T. et al Reference values for quantitative sensory testing in children and adolescents: developmental and gender differences of somatosensory perception.. Pain 2010; 149: 76-88 doi: 10.1016/j.pain.2010.01.011
• 5 Christoph T, De Vry J, Tzschentke TM. Tapentadol, but not morphine, selectively inhibits diseaserelated thermal hyperalgesia in a mouse model of diabetic neuropathic pain.. Neurosci Lett 2010; 470: 91-94 doi: 10.1016/j.neulet.2009.12.020
• 6 Cox JJ, Reimann F, Nicholas AK. et al An SCN9A channelopathy causes congenital inability to experience pain.. Nature 2006; 444: 894-498 doi: 10.1038/nature05413
• 7 Cruccu G, Sommer C, Anand P. et al EFNS guidelines on neuropathic pain assessment: revised 2009.. Eur J Neurol 2010; 17: 1010-1018 doi:10.111/j.1468-1331.2010.02969.x
• 8 Demant DT, Lund K, Finnerup NB. et al Pain relief with lidocaine 5 % patch in localized peripheral neuropathic pain in relation to pain phenotype: a randomised, double-blind, and placebocontrolled, phenotype panel study.. Pain 2015; 156: 2234-2244 doi: 10.1097/j.pain.0000000000000266
• 9 Demant DT, Lund K, Vollert J. et al The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study.. Pain 2014; 155: 2263-73 doi: 10.1016/j.pain.2014.08.014
• 10 Edwards RR, Haythornthwaite JA, Tella P. et al Basal heat pain thresholds predict opioid analgesia in patients with postherpetic neuralgia.. Anesthesiology 2006; 104: 1243-1248
• 11 Eisenberg E, Midbari A, Haddad M, Pud D. Predicting the analgesic effect to oxycodone by ‘static’ and ‘dynamic’ quantitative sensory testing in healthy subjects.. Pain 2010; 151: 104-109 doi: 10.1016/j.pain.2010.06.025
• 12 Facer P, Casula MA, Smith GD. et al Differential expression of the capsaicin receptor TRPV1 and related novel receptors TRPV3, TRPV4 and TRPM8 in normal human tissues and changes in traumatic and diabetic neuropathy.. BMC Neurol 2007; 07: 11 doi:10.1186/147-2377-7-11
• 13 Finnerup NB, Attal N, Haroutounian S. et al Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis.. Lancet Neurol 2015; 14: 162-173 doi: 10.1016/S1474-4422(14)70251-0
• 14 Finnerup NB, Sindrup SH, Bach FW. et al Lamotrigine in spinal cord injury pain: a randomized controlled trial.. Pain 2002; 96: 375-383 doi: 10.1016/S0304-3959(01)00484-5
• 15 Förster M, Helfert S, Dierschke R. et al Evaluation of the antihyperalgesic effect of tapentadol in two human evoked pain models – the TapCap-Mentho pilot trial.. Expert Opin Pharmacother 2016; 17: 1717-1725 doi: 10.1080/14656566.2016.1201071
• 16 Freynhagen R, Baron R, Gockel U, Tölle TR. Pain-DETECT: a new screening questionnaire to identify neuropathic components in patients with back pain.. Curr Med Res Opin 2006; 22: 1911-1920 doi: 10.1185/030079906X132488
• 17 www.dgn.org/leitlinien/2373-ll62-2012-pharmakologisch-nicht-interventionelle-therapie-chronisch-neuropathischer-schmerzen (letzter Zugriff: 30.05.2018)
• 18 www.awmf.org/leitlinien/detail/ll/030-114.html (letzter Zugriff: 30.05.2018)
• 19 Holbech JV, Bach FW, Finnerup NB. et al Pain phenotype as a predictor for drug response in painful polyneuropathy-a retrospective analysis of data from controlled clinical trials.. Pain 2016; 157: 1305-1313 doi: 10.1097/j.pain.0000000000000563
• 20 Krumova EK, Zeller M, Westermann A, Maier C. Lidocaine patch (5 %) produces a selective, but incomplete block of Aδ and C fibers.. Pain 2012; 153: 273-280 doi: 10.1016/j.pain.2011.08.020
• 21 La Cesa S, Tamburin S, Tugnoli V. et al How to diagnose neuropathic pain? The contribution from clinical examination, pain questionnaires and diagnostic tests.. Neurol Sci 2015; 36: 2169-2175 doi: 10.1007/s10072-015-2382-z
• 22 Leone C, Biasiotta A, La Cesa S. et al Pathophysiological mechanisms of neuropathic pain.. Future Neurology 2011; 06: 497-509 doi: 10.2217/fnl.11.23
• 23 McDonnell A, Schulman B, Ali Z. et al Inherited erythromelalgia due to mutations in SCN9A: natural history, clinical phenotype and somatosensory profile.. Brain 2016; 139 (Pt 4) 1052-1065 doi: 10.1093/brain/aww007
• 24 Magerl W, Krumova EK, Baron R. et al Reference data for quantitative sensory testing (QST): refined stratification for age and a novel method for statistical comparison of group data.. Pain 2010; 151: 598-605 doi: 10.1016/j.pain.2010.07.026
• 25 Maier C, Baron R, Tölle TR. et al Quantitative sensory testing I; the German Research Network on Neuropathic Pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes.. Pain 2010; 150: 439-450 doi: 10.1016/j.pain.2010.05.002
• 26 Mainka T, Malewicz NM, Baron R. et al Presence of hyperalgesia predicts analgesic efficacy of topically applied capsaicin 8 % in patients with peripheral neuropathic pain.. Eur J Pain 2016; 20: 116-119 doi: 10.1002/ejp.703
• 27 Max MB. Towards physiologically based treatment of patients with neuropathic pain.. Pain 1990; 42: 131-137 doi: 10.1016/0304-3959(90)91156-D
• 28 Nickel FT, Seifert F, Lanz S, Maihöfner C. Mechanisms of neuropathic pain.. Eur Neuropsychopharmacol 2012; 22: 81-91 doi: 10.1016/j.euroneuro.2011.05.005
• 29 Pfau DB, Krumnova EK, Trede RD. et al Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): reference data for the trunk and application in patients with chronic postherpetic neuralgia.. Pain 2014; 155: 1002-1015 doi: 10.1016/j.pain.2014.02.004
• 30 Simpson DM, Schifitto G, Clifford DB. et al Pregabalin for painful HIV neuropathy: a randomized, double-blind, placebocontrolled trial.. Neurology 2010; 74: 413-420 doi: 10.1212/WNL.0b013e3181ccc6ef
• 31 Treede RD, Jensen TS, Campbell JN. et al Neuropathic pain: redefinition and a grading system for clinical and research purposes.. Neurology 2008; 70: 1630-1635 doi: 10.1212/01.wnl.0000282763.29778.59
• 32 van Hecke O, Austin SK, Khan RA. et al Neuropathic pain in the general population: a systematic review of epidemiological studies.. Pain 2014; 155: 654-662 doi: 10.1016/j.pain.2013.11.013
• 33 Vollert J, Kramer M, Barosso A. et al Symptom profiles in the painDETECT Questionnaire in patients with peripheral neuropathic pain stratified according to sensory loss in quantitative sensory testing.. Pain 2016; 157: 1810-1818 doi: 10.1097/j.pain.0000000000000588
• 34 Walk D, Sehgal N, Moeller-Bertram T. et al Quantitative sensory testing and mapping: a review of nonautomated quantitative methods for examination of the patient with neuropathic pain.. Clin J Pain 2009; 25: 632-640 doi: 10.1097/AJP.0b013e3181a68c64
• 35 Wasner G, Kleinert A, Binder A. et al Postherpetic neuralgia: topical lidocaine is effective in nociceptor-deprived skin.. J Neurol 2005; 252: 677-686 doi: 10.1007/s00415-005-0717-z
• 36 Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain.. Science 2000; 288: 1765-1769 doi: 10.1126/science.288.5472.1765
• 37 Yarnitsky D, Granot M, Granovsky Y. Pain modulation profile and pain therapy: between pro- and antinociception.. Pain 2014; 155: 663-665 doi: 10.1016/j.pain.2013.11.005
• 38 Yarnitsky D, Granot M, Nahman-Averbuch H. et al Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy.. Pain 2012; 153: 1193-1198 doi: 10.1016/j.pain.2012.02.021