Dohrn MF

OpenAlex Profile
2
EM Publications
17
h-index
(940 citations, 111 total works)

Research Topics

Hereditary Neurological Disorders (33) Pain Mechanisms and Treatments (19) Genetic Neurodegenerative Diseases (17) Botulinum Toxin and Related Neurological Disorders (17) Ion channel regulation and function (11)

Erythromelalgia Publications

Assessing the impact of pain-linked Nav1.7 variants: An example of two variants with no biophysical effect.

Le Cann K, Meents JE, Sudha Bhagavath Eswaran V, Dohrn MF, Bott R , et al.
Channels (Austin, Tex.) •

Mutations in the voltage-gated sodium channel Nav1.7 are linked to human pain. The Nav1.7/N1245S variant was described before in several patients suffering from primary erythromelalgia and/or olfactory hypersensitivity. We have identified this variant in a pain patient and a patient suffering from severe and life-threatening orthostatic hypotension. In addition, we report a female patient suffering from muscle pain and carrying the Nav1.7/E1139K variant. We tested both Nav1.7 variants by whole-cell voltage-clamp recordings in HEK293 cells, revealing a slightly enhanced current density for the N1245S variant when co-expressed with the β1 subunit. This effect was counteracted by an enhanced slow inactivation. Both variants showed similar voltage dependence of activation and steady-state fast inactivation, as well as kinetics of fast inactivation, deactivation, and use-dependency compared to WT Nav1.7. Finally, homology modeling revealed that the N1245S substitution results in different intramolecular interaction partners. Taken together, these experiments do not point to a clear pathogenic effect of either the N1245S or E1139K variant and suggest they may not be solely responsible for the patients' pain symptoms. As discussed previously for other variants, investigations in heterologous expression systems may not sufficiently mimic the pathophysiological situation in pain patients, and single nucleotide variants in other genes or modulatory proteins are necessary for these specific variants to show their effect. Our findings stress that biophysical investigations of ion channel mutations need to be evaluated with care and should preferably be supplemented with studies investigating the mutations in their context, ideally in human sensory neurons.

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[Neuropathic pain syndromes and channelopathies].

Dohrn MF, Lampert A, Üçeyler N, Kurth I
Der Internist •

The causes for neuropathic pain are manifold and remain unexplained in the majority of cases. In recent years a growing number of pain syndromes have been attributed to mutations in genes encoding voltage-gated sodium channels. Hence, this group of rare diseases should be considered in the differential diagnostics of neuropathic pain. Evaluation of topic-related literature and discussion of own experiences as well as consideration of current guidelines. Alterations in the electrical excitability of nociceptive neurons by pathogenic mutations in sodium channels lead to disease patterns, such as small fiber neuropathy and various pain syndromes. This article summarizes the knowledge on these genetic diseases and discusses the differential diagnosis of neuropathic pain. Current treatment concepts are presented and the predominantly experimental approaches to targeted modulation of sodium channels are discussed. The treatment of patients with chronic neuropathic pain requires interdisciplinary cooperation and is often difficult due to an unsatisfactory treatment response. Increasing knowledge on rare genetically determined channelopathies can contribute to the development of novel pharmaceuticals since ion channels are central players in the processing of pain.

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