Clonidine reduces the excitability of spinal dorsal horn neurones.
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 Adelta 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 microM) of clonidine, but not in adapting- or single-spike-firing neurones. High concentrations of clonidine (700 microM) 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 microM) 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.
Wolff
M
M
Clinic for Anaesthesiology, Intensive Care Medicine, and Pain Therapy, Giessen, Germany. matthias.wolff@physiologie.med.uni-giessen.de
Heugel
P
P
Hempelmann
G
G
Scholz
A
A
Mühling
J
J
Olschewski
A
A
D000200:Action Potentials / Q000187:drug effects; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism
D000700:Analgesics; D024642:Potassium Channels, Voltage-Gated; D012964:Sodium; D003000:Clonidine; D011188:Potassium