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Intravenously administered lidocaine in therapeutic doses increases the intraspinal release of acetylcholine in rats
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Försöksdjursvetenskap.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Försöksdjursvetenskap.
2002 (engelsk)Inngår i: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 317, nr 2, s. 93-6Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Elsevier , 2002. Vol. 317, nr 2, s. 93-6
Emneord [en]
Lidocaine; Spinal cord; Pain; Microdialysis; Acetylcholine; Muscarinic; Nicotinic
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-7227DOI: 10.1016/S0304-3940(01)02440-5OAI: oai:DiVA.org:uu-7227DiVA, id: diva2:131039
Tilgjengelig fra: 2006-10-24 Laget: 2006-10-24 Sist oppdatert: 2017-12-14bibliografisk kontrollert
Inngår i avhandling
1. Acetylcholine in Spinal Pain Modulation: An in vivo Study in the Rat
Åpne denne publikasjonen i ny fane eller vindu >>Acetylcholine in Spinal Pain Modulation: An in vivo Study in the Rat
2005 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2005. s. 55
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 19
Emneord
Laboratory animals, Pain, Nociception, Antinociception, Acetylcholine, Muscarinic, Nicotinic, Spinal cord, Microdialysis, Försöksdjursvetenskap
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-4834 (URN)91-554-6178-6 (ISBN)
Disputas
2005-04-22, B41, BMC, Husargatan 3, Uppsala, 09:15 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2005-03-30 Laget: 2005-03-30 Sist oppdatert: 2009-10-14bibliografisk kontrollert

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