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ANALGESIA

The Effect of Peripherally Administered CDP-Choline in an Acute Inflammatory Pain Model: The Role of 7 Nicotinic Acetylcholine Receptor

Mine Sibel Gurun, MD, PhD^*, Renee Parker, BS, James C. Eisenach, MD, PhD, and Michelle Vincler, PhD

From the *Department of Pharmacology and Clinical Pharmacology, Uludag University, Bursa, Turkey; and Department of Anesthesiology, Wake Forest University, School of Medicine, Winston-Salem, North Carolina.

Address correspondence and reprint requests to Mine Sibel Gurun, MD, PhD, Department of Pharmacology and Clinical Pharmacology, Uludag University, 16059, Görükle, Bursa, Turkey. Address e-mail to sgurun{at}uludag.edu.tr.

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 7 nicotinic acetylcholine receptors (7nAChR). Previous reports also suggest that the peripheral cholinergic system has an antiinflammatory role mediated by 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 µL, 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 µL.

RESULTS: CDP-choline (1, 2.5, 5 µmol; 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 ipsilateral inflammation. Methyllycaconitine (100 nmol), a selective 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 µmol) 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- 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 7nAChRs in the carrageenan-induced inflammatory pain model.