Clonidine reduces the excitability of spinal dorsal horn neurones. 2007

M Wolff, and P Heugel, and G Hempelmann, and A Scholz, and J Mühling, and A Olschewski
Clinic for Anaesthesiology, Intensive Care Medicine, and Pain Therapy, Giessen, Germany. matthias.wolff@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 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.

UI MeSH Term Description Entries
D008297 Male Males
D011188 Potassium An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D003000 Clonidine An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION. Catapres,Catapresan,Catapressan,Chlophazolin,Clofelin,Clofenil,Clonidine Dihydrochloride,Clonidine Hydrochloride,Clonidine Monohydrobromide,Clonidine Monohydrochloride,Clopheline,Dixarit,Gemiton,Hemiton,Isoglaucon,Klofelin,Klofenil,M-5041T,ST-155,Dihydrochloride, Clonidine,Hydrochloride, Clonidine,M 5041T,M5041T,Monohydrobromide, Clonidine,Monohydrochloride, Clonidine,ST 155,ST155
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000700 Analgesics Compounds capable of relieving pain without the loss of CONSCIOUSNESS. Analgesic,Anodynes,Antinociceptive Agents,Analgesic Agents,Analgesic Drugs,Agents, Analgesic,Agents, Antinociceptive,Drugs, Analgesic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012964 Sodium A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. Sodium Ion Level,Sodium-23,Ion Level, Sodium,Level, Sodium Ion,Sodium 23
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats

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