The effect of peripherally administered cdp-choline in an acute inflammatory pain model: The role of α7 nicotinic acetylcholine receptor

Abstract

BACKGROUND: CDP-choline (citicholine; cytidine-5'-diphosphate choline) is an endogenously produced nucleotide which, when injected intracerebroventricularly, exerts an antinociceptive effect in acute pain models mediated by central cholinergic mechanisms and alpha 7 nicotinic acetylcholine receptors (alpha 7nAChR). Previous reports also suggest that the peripheral cholinergic system has an antiinflammatory role mediated by alpha 7nAChRs on macrophages.

METHODS: We used male Sprague-Dawley rats to assess the antihypersensitivity and antiinflammatory effect of CDP-choline after intraplantar injection of carrageenan (100 mu L, 2%). Mechanical paw withdrawal thresholds and paw thickness were measured by Randall-Selitto testing and microcallipers, respectively. All drugs were administered intraplantarly in a volume 50 mu L.

RESULTS: CDP-choline (1, 2.5, 5 mu mol; intraplantar) increased the mechanical paw withdrawal threshold and decreased paw edema in a dose- and time-dependent manner in the carrageenan-injected hindpaw. CDP-choline administration to the noninflamed contralateral hindpaw did not alter ipsdateral inflammation. Methyllycaconitine (100 nmol), a selective alpha 7nAChR antagonist, completely blocked the effects of CDP-choline when administered to the inflamed hindpaw. However, the administration of methyllycaconitine to the contralateral hindpaw did not block the effects of CDP-choline in the ipsilateral paw. The administration of CDP-choline (5 mu mol) 10 min after carrageenan administration to the ipsilateral hindpaw did not reduce swelling and edema but did significantly reduce hypersensitivity. Treatment with CDP-choline decreased tumor necrosis factor-a production in the rat paw tissue after carrageenan.

CONCLUSIONS: The results of this study suggest that intraplantar CDP-choline has antihypersensitivity and antiinflammatory effects mediated via alpha 7nAChRs in the carrageenan-induced inflammatory pain model.