Axonal Change, Neuronal, Pain
Conditions
Keywords
neuropathy, axonal excitability, myelinated nerve, human, ectopic discharge, flupirtine
Brief summary
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.
Interventions
DRUGflupirtine
Potassium channel opener (SNEPCO)
Sponsors
Ludwig-Maximilians - University of Munich
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* voluntarily * age \> 18 years old
Exclusion criteria
* current use of medication (e.g. analgetics, antiepileptics, antidepressants, etc.) * prevailing organic disease (e.g. diabetes, vascular or neurologic illness, etc.) * previous physical trauma of the forearm (e.g. burning, surgery) * primary organ failure * pregnancy and lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Axonal Excitability as assessed with QTrac | Change of neuronal excitability from Baseline (before) to two hours after intervention | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ectopic Discharge | Change of neuronal excitability from Baseline (before) to two hours after intervention | Further secondary outcome measures were power content for the surface EMG and the ranked summed scores for the McGill pain questionnaire. |
Countries
Germany
Outcome results
None listed