Clonidine reduces the excitability of spinal dorsal horn neurones
1 Clinic for Anaesthesiology, Intensive Care Medicine, and Pain Therapy, Giessen, Germany
2 Department of Physiology, Justus-Liebig-University, D-35392 Giessen, Germany
3 Department of Anaesthesiology and Intensive Care Medicine, Medical University Graz, Austria
* Corresponding author: Clinic for Anaesthesiology Intensive Care Medicine, and Pain Therapy, Rudolf-Buchheim-Straße 7, 35392 Giessen, Germany. E-mail: matthias.wolff{at}physiologie.med.uni-giessen.de
BACKGROUND: Clonidine has often been applied in combination with local anaesthetics for spinal or epidural anaesthesia. This study was designed to investigate the local anaesthetic-like action of clonidine in superficial dorsal horn neurones. The superficial laminae of the dorsal horn contain three groups of neurones: tonic-, adapting-, and single-spike-firing neurones which are important neuronal structures for pain transmission, receiving most of their primary sensory input from A
and C fibres.
METHODS: Whole cell patch clamp recordings from spinal cord slices of Wistar rats were used to study the action of clonidine on the generation of single and series of action potentials. Voltage clamp recordings in isolated somata were performed to study the effect of clonidine on voltage-gated Na+ and different types of K+ currents.
RESULTS: Firing frequencies of trains of action potentials in tonic-firing neurones are reduced at low concentrations (10 µM) of clonidine, but not in adapting- or single-spike-firing neurones. High concentrations of clonidine (700 µM) are necessary to modify the shape of single action potentials. Low concentrations of clonidine shift the steady-state inactivation curve of Na+ currents to more negative potentials. At clinical concentrations (6–100 µM) clonidine partially inhibits voltage-gated Na+ and K+ channels.
CONCLUSIONS: Clonidine suppresses the generation of action potentials in tonic-firing spinal dorsal horn neurones. This may be explained, in part, by an interaction with voltage-gated Na+ and K+ currents. Clonidine could therefore contribute to analgesia during local anaesthesia.
Keywords: ion channels, voltage gated; pharmacology, clonidine; spinal cord, sensory block
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