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Intravenously administered oxotremorine and atropine, in doses known to affect pain threshold, affect 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: Pharmacology and Toxicology, ISSN 0901-9928, Vol. 90, no 4, 187-192 p.Article in journal (Refereed) Published
Abstract [en]

Abstract:Both systemically and intrathecally administered cholinergic agonists produce antinociception while cholinergic antagonists decrease pain threshold. The mechanism and the site of action of these substances are not known. In the present study it was hypothesized that systemically administered muscarinic agonists and antagonists modify nociceptive threshold by affecting intraspinal release of acetylcholine (ACh). Catheters were inserted into the femoral vein in rats maintained on isoflurane anaesthesia for administration of oxotremorine (10–300 μg/kg) and atropine (0.1, 10, 5000 μg/kg). Spinal microdialysis probes were placed intraspinally at approximately the C2–C5 spinal level for sampling of acetylcholine and dialysis delivery of atropine (0.1, 1, 10 nM). Additionally, the tail-flick behaviour was tested on conscious rats injected intraperitoneally with saline, atropine (10, 100 and 5000 μg/kg), or subcutaneously with oxotremorine (30, 100, 300 μg/kg). Subcutaneous administration of oxotremorine (30, 100, 300 μg/kg) significantly increased the tail-flick latency. These doses of oxotremorine dose-dependently increased the intraspinal release of acetylcholine. Intravenously administered atropine, in a dose that produced hyperalgesia (5000 μg/kg) in the tail-flick test, significantly decreased the intraspinal release of acetylcholine. Our results suggest an association between pain threshold and acetylcholine release in spinal cord. It is also suggested that an approximately 30% increase in basal ACh release produces antinociception and that a 30% decrease in basal release produces hyperalgesia.

Place, publisher, year, edition, pages
Blackwell , 2002. Vol. 90, no 4, 187-192 p.
National Category
Biomedical Laboratory Science/Technology
Identifiers
URN: urn:nbn:se:uu:diva-7215DOI: 10.1034/j.1600-0773.2002.900403.xOAI: oai:DiVA.org:uu-7215DiVA: diva2:131038
Available from: 2006-10-18 Created: 2006-10-18 Last updated: 2009-10-13Bibliographically 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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