NDLI: Antinociceptive and anti-inflammatory effects of choline in a mouse model of postoperative pain.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Rowley, T. J. McKinstry, A. Greenidge, E. Smith, W. Flood, P.
Description	Country affiliation: United States Author Affiliation: Rowley TJ ( Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.)
Abstract	BACKGROUND: Choline is a dietary supplement that activates alpha7 nicotinic receptors. alpha7 nicotinic activation reduces cytokine production by macrophages and has antinociceptive activity in inflammatory pain models. We hypothesized that systemic administration of choline would reduce the inflammatory response from macrophages and have antinociceptive efficacy in a murine model of postoperative pain. METHODS: We studied the response of wild-type and alpha7 nicotinic knockout mice to heat and punctate pressure after a model surgical procedure. We investigated the effect of genotype and choline treatment on alpha-bungarotoxin binding to, and their production of tumour necrosis factor (TNF) from, macrophages. RESULTS: Choline provided moderate antinociception. The ED(50) for choline inhibition of heat-induced allodynia was 1.7 mg kg(-1) h(-1). The ED(50) for punctate pressure threshold was 4.7 mg kg(-1) h(-1) choline. alpha7 nicotinic knockout mice had no change in hypersensitivity to heat or pressure and were significantly different from littermate controls when treated with choline 5 mg kg(-1) h(-1) (P<0.05, 0.01). Choline 100 mM reduced binding of alpha-bungarotoxin to macrophages by 72% and decreased their release of TNF by up to 51 (sd 11)%. There was no difference by genotype in the inhibition of TNF release by choline. CONCLUSIONS: Systemic choline is a moderately effective analgesic via activation of alpha7 nicotinic acetylcholine receptors. The antinocicepive effect may not be mediated by a reduction of TNF pathway cytokine release from macrophages. Although choline at millimolar concentrations clearly inhibits the release of TNF, this effect is not alpha7 subunit-dependent and occurs at concentrations likely higher than reached systemically in vivo.
File Format	HTM / HTML
ISSN	00070912
e-ISSN	14716771
DOI	10.1093/bja/aeq113
Journal	British Journal of Anaesthesia
Issue Number	2
Volume Number	105
Language	English
Publisher	Oxford University Press
Publisher Date	2010-08-01
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Discipline Anesthesiology Analgesics, Non-narcotic Therapeutic Use Anti-inflammatory Agents, Non-steroidal Choline Pain, Postoperative Prevention & Control Animals Drug Evaluation, Preclinical Hot Temperature Macrophages, Peritoneal Drug Effects Metabolism Mice Mice, Inbred C57bl Mice, Knockout Models, Animal Physical Stimulation Receptors, Nicotinic Deficiency Genetics Tumor Necrosis Factor-alpha Biosynthesis Alpha7 Nicotinic Acetylcholine Receptor Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Anesthesiology and Pain Medicine

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