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Slow axonal Kv7 potassium channels are found along unmyelinated axons and at the nodes of Ranvier of myelinated axons in peripheral nerve. As such the pharmacological activation of Kv7 channels offers a potential means of reducing the excitability of peripheral axons. To determine whether this is the case for human peripheral myelinated axons, the effect of the Kv7 channel agonist flupirtine on the electrical excitability of A fibres was examined in both isolated segments of human sural nerve in vitro and in motor axons of the median nerve supplying abductor pollicus brevis in vivo. Axonal excitability was assessed in 21 human sural nerve fascicles in vitro and in 20 volunteers in vivo using threshold tracking in QTRAC (© Institute of Neurology, London, UK). Strength-duration time constant, rheobase current, relative refractory period (RRP), post spike superexcitability at 5 and 7 ms and threshold electrotonus over the 90 100 ms period were used as indices of electrical excitability. In addition, suppression of ectopic discharge in a model of upper limb ischaemia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo first | Experimental | Volunteers receive placebo first and after a cross-over period of at least 7 days flupirtine second. On the days of the experiment outcome is taken as the change in excitability from Baseline (all measures before intervention) to a timepoint two hours after intervention |
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| Flupirtine first | Experimental | Volunteers receive flupirtine first and after a cross-over period of at least 7 days placebo second. On the days of the experiment outcome is taken as the change in excitability from Baseline (all measures before intervention) to a timepoint two hours after intervention |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| flupirtine | Drug | Potassium channel opener (SNEPCO) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Axonal Excitability as assessed with QTrac | The primary outcome parameter of axonal excitability was the relative refractory period (RRP) as assessed with threshold tracking techniques. Strength-duration time constant, rheobase current, refractoriness determined at 2 and 2.5 ms, superexcitability at 7 ms and threshold electrotonus over the 90 100 ms period were used as secondary outcome measures. | Change of neuronal excitability from Baseline (before) to two hours after intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Ectopic Discharge | Further secondary outcome measures were power content for the surface EMG and the ranked summed scores for the McGill pain questionnaire. | Change of neuronal excitability from Baseline (before) to two hours after intervention |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dominik Irnich, MD, PhD | Multidisciplinary Pain Unit Department of Anaesthesiology University of Munich Pettenkoferstr. 8a D-80336 Munich | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Multidisciplinary Pain Unit Department of Anaesthesiology University of Munich Pettenkoferstr. 8a | Munich | Bavaria | 80336 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23394517 | Result | Fleckenstein J, Sittl R, Averbeck B, Lang PM, Irnich D, Carr RW. Activation of axonal Kv7 channels in human peripheral nerve by flupirtine but not placebo - therapeutic potential for peripheral neuropathies: results of a randomised controlled trial. J Transl Med. 2013 Feb 8;11:34. doi: 10.1186/1479-5876-11-34. |
| Label | URL |
|---|---|
| Homepage of the respective Journal | View source |
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| ID | Term |
|---|---|
| D010146 | Pain |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C034161 | flupirtine |
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