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We would like to thank you for your interest in the treatment of chronic neuropathic pain. Due to limitations in text length, a CME article cannot provide comprehensive information about all details. Thus, suggestions of readers regarding topics relevant to clinical practice are even more important, and we are happy to discuss them.

The meta-analysis by Finnerup et al. published in Lancet Neurology mentions for the substance classes of tricyclic antidepressants (TCAs) 16 positive studies for the agents amitriptyline, clomipramine, desipramine, imipramine, maprotiline, and nortriptyline (1). Nevertheless, a general recommendation for the use of TCAs is made which is not based on the evidence supporting the efficacy of individual substances, but on the principle postulated for the treatment of neuropathic pain with TCAs which assumes the underlying mechanism of action is a modification of the functionality of descending noradrenergic (and serotonergic) systems (2). As this active principle is shared by all members of the TCA group, a general recommendation is made (1). The reason for not mentioning the SSNRI milnacipran is that for this substance—in contrast to duloxetine and venlafaxine—no studies evaluating its use in patients with neuropathic pain are available. Providing a detailed list of market approvals—and these can vary between products of different manufacturers even if the active ingredient is the same—is beyond the scope of a CME article of this type. For this reason, we explicitly highlighted this fact.

A proper diagnosis precedes the use of any medication in pain therapy. Therefore, the diagnostic evaluation is the first step of the treatment algorithm presented by us. Thus, we agree with Mr. Hoffmann that any uncritical prescription should be avoided, even though this was not stated by us in our article. Rather it is important to ensure that treatment is provided for one of the approved indications, e.g. neuropathic pain.

The concept of “mixed pain“ represents a constellation in pain patients which is accepted by the European Medicines Agency in its guideline for the development of pain therapies (3). Radiculopathy is a pain syndrome which often does not respond sufficiently to treatment, as is the case with other conditions, for example chemotherapy-induced polyneuropathy (1). A neuropathic pain component is not present in all back pain patients. Rather, as we have highlighted, its prevalence lies in the range of 16 to 25%. Therefore, it is clear that not in every patient back pain can be alleviated with drugs targeting neuropathic pain. Furthermore, we have explicitly stated the efficacy of pregabalin for the treatment of neuropathic pain, using the number needed to treat (NNT). An NNT of 7.7 clearly shows that treatment with pregabalin (alone) cannot achieve adequate pain reduction in all patients with neuropathic pain. Thus, the aim of our CME article was to highlight the difficulties in the pharmacological therapy of chronic neuropathic pain and to educate about possible approaches to alleviating this pain (4).

DOI: 10.3238/arztebl.2017.0193

PD Dr. med. Andreas Binder, Prof. Dr. med. Ralf Baron
Sektion Neurologische Schmerzforschung und -therapie
Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany
andreas.binder@uksh.de

Conflict of interest statement
PD Dr. Binder has served as a paid consultant for Pfizer, Grünenthal, Astellas, and Mundipharma. He has received reimbursement of meeting participation fees and of travel and accommodation expenses from Astellas, Pfizer, and Grünenthal. He has been paid for the preparation of continuing medical education events by Astellas, Pfizer, and Grünenthal. He has received financial support from Grünenthal and Pfizer for a research project that he initiated.

Prof. Baron has served as a paid consultant for Pfizer, Genzyme, Grünenthal, Mundipharma, Allergan, Sanofi Pasteur, Medtronic, Eisai, Lilly, Boehringer Ingelheim, Astellas, Novartis, Bristol Myers-Squibb, Biogenidec, AstraZeneca, Merck, Abbvie, Daiichi Sankyo, Glenmark Pharmaceuticals, Seguris, Teva, Genetech, Galapagos, and Kyowa Kirin GmbH. He has received payment for authorship and co-authorship of publications on topics related to that of this article from Pfizer, Genzyme, Grünenthal, Mundipharma, Sanofi Pasteur, Medtronic, Eisai, Lilly, Boehringer Ingelheim, Astellas, Desitin, Teva Pharma, Bayer-Schering MSD, Seguris, Novartis, Bristol Myers-Squibb, Biogenidec, AstraZeneca, Merck, Abbvie, Daiichi Sankyo, and Glenmark Pharmaceuticals.

He has received reimbursement of meeting participation fees and of travel and accommodation expenses, as well as lecture honoraria, from Pfizer, Genzyme, Grünenthal, Mundipharma, Sanofi Pasteur, Medtronic, Eisai, Lilly, Boehringer Ingelheim, Astellas, Desitin, Teva Pharma, Bayer-Schering, MSD, and bioCSL. He has received payment for carrying out clinical trials on behalf of Grünenthal and Pfizer. He has received financial support from Pfizer, Genzyme, Grünenthal, and Mundipharma for a research project that he initiated.

1.
Finnerup NB, Attal N, Haroutounian S, et al.: Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis. Lancet Neurol 2015; 14: 162–73 CrossRef
2.
Baron R, Binder A, Wasner G: Neuropathic pain: Diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol 2010; 9: 807–19 CrossRef
3.
Guideline on the clinical development of medicinal products intended fort the treatment of pain. 6.2.4. Mixed Pain. European Medicines Agency Science Medicines Health. 17 Dezember 2015; EMA/CHMP/970057/2011.
4.
Binder A, Baron R: The pharmacological therapy of chronic neuropathic pain. Dtsch Arztebl Int 2016; 113: 616–26 VOLLTEXT
1. Finnerup NB, Attal N, Haroutounian S, et al.: Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis. Lancet Neurol 2015; 14: 162–73 CrossRef
2. Baron R, Binder A, Wasner G: Neuropathic pain: Diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol 2010; 9: 807–19 CrossRef
3. Guideline on the clinical development of medicinal products intended fort the treatment of pain. 6.2.4. Mixed Pain. European Medicines Agency Science Medicines Health. 17 Dezember 2015; EMA/CHMP/970057/2011.
4.Binder A, Baron R: The pharmacological therapy of chronic neuropathic pain. Dtsch Arztebl Int 2016; 113: 616–26 VOLLTEXT

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