Effect of the Kv7-channel Opener Flupirtine on the Excitability of Human Peripheral Myelinated Axons in Vivo

Ludwig-Maximilians - University of Munich20 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Masking

QUADRUPLE

Enrollment

Conditions

Axonal Change, Neuronal Pain

Interventions

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: Change of neuronal excitability from Baseline (before) to two hours after intervention

Secondary Outcomes

Ectopic Discharge

Further secondary outcome measures were power content for the surface EMG and the ranked summed scores for the McGill pain questionnaire.