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Intravenously administered lidocaine in therapeutic doses increases the intraspinal release of acetylcholine in rats
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
2002 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 317, no 2, 93-6 p.Article in journal (Refereed) Published
Abstract [en]

The local anesthetic lidocaine suppresses different pain conditions when administered systemically. Part of the antinociceptive effect appears to be mediated via receptor mechanisms. We have previously shown that muscarinic and nicotinic agonists that produce antinociception increase the intraspinal release of acetylcholine. In the present study it was hypothesized that systemically administered lidocaine is acting through the same mechanisms as cholinergic agonists and affects the intraspinal release of acetylcholine. Microdialysis probes were placed in anesthetized rats for sampling of acetylcholine. Ten and 30 mg/kg lidocaine injected intravenously significantly increased the intraspinal release of acetylcholine. The effect of lidocaine could be reduced by pretreatment with intraspinally administered atropine or mecamylamine. Our results suggest that the antinociceptive effect produced by systemically administered lidocaine is mediated through an action on muscarinic and nicotinic receptors.

Place, publisher, year, edition, pages
Elsevier , 2002. Vol. 317, no 2, 93-6 p.
Keyword [en]
Lidocaine; Spinal cord; Pain; Microdialysis; Acetylcholine; Muscarinic; Nicotinic
National Category
Biomedical Laboratory Science/Technology
Identifiers
URN: urn:nbn:se:uu:diva-7227DOI: 10.1016/S0304-3940(01)02440-5OAI: oai:DiVA.org:uu-7227DiVA: diva2:131039
Available from: 2006-10-24 Created: 2006-10-24 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Acetylcholine in Spinal Pain Modulation: An in vivo Study in the Rat
Open this publication in new window or tab >>Acetylcholine in Spinal Pain Modulation: An in vivo Study in the Rat
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The spinal cord is an important component in the processing and modulation of painful stimuli. Nerve signals from the periphery are relayed and further conducted to the brain (nociception) in the spinal cord, and the most essential modulation of painful information (antinociception) occurs here. Several neurotransmitters are involved in spinal pain modulation, among them acetylcholine. However, the role of acetylcholine has previously been little investigated.

In the present thesis, the acetylcholine release in the spinal cord was studied in vivo. By using spinal microdialysis on anaesthetised rats, the effects on the intraspinal acetylcholine release of various receptor ligands and analgesic agents were examined. This, together with pain behavioural tests and in vitro pharmacological assays, was used to evaluate the role of acetylcholine in spinal pain modulation. The four studies in this thesis resulted in the following conclusions:

An increased release of spinal acetylcholine is associated with an elevated pain threshold, while a decreased acetylcholine release is associated with hyperalgesia, as seen after systemic treatment with a muscarinic agonist and an antagonist.

Lidocaine is a potent analgesic when given systemically. It was found to produce an increase of intraspinal acetylcholine after intravenous injection of analgesic doses. This effect was attenuated after muscarinic, and abolished after nicotinic, receptor blockade.

Various a2-adrenergic ligands, associated with nociceptive or antinociceptive effects, were found to affect intraspinal acetylcholine release via action on nicotinic receptors.

Finally, the involvement of spinal acetylcholine in the analgesic effects of aspirin and paracetamol was examined. It was found that spinal acetylcholine could participate in the analgesic effects of aspirin, but not of paracetamol.

The present thesis provides data that clearly demonstrate a relationship between intraspinal acetylcholine and antinociception, and elucidate interactions between acetylcholine and other mechanisms that mediate antinociception in the spinal cord.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 55 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 19
Keyword
Laboratory animals, Pain, Nociception, Antinociception, Acetylcholine, Muscarinic, Nicotinic, Spinal cord, Microdialysis, Försöksdjursvetenskap
National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:uu:diva-4834 (URN)91-554-6178-6 (ISBN)
Public defence
2005-04-22, B41, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2005-03-30 Created: 2005-03-30 Last updated: 2009-10-14Bibliographically approved

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