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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.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.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.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.
View details for DOI 10.1093/bja/aeq113
View details for Web of Science ID 000280013800016
View details for PubMedID 20511332