The effect of peripherally administered CDP-choline in an acute inflammatory pain model: the role of alpha7 nicotinic acetylcholine receptor.
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 alpha7 nicotinic acetylcholine receptors (alpha7nAChR). Previous reports also suggest that the peripheral cholinergic system has an antiinflammatory role mediated by alpha7nAChRs 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 microL, 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 microL.


RESULTS
CDP-choline (1, 2.5, 5 micromol; 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 alpha7nAChR 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 micromol) 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-alpha 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 alpha7nAChRs in the carrageenan-induced inflammatory pain model.
Department of Pharmacology and Clinical Pharmacology, Uludag University, Görükle, Bursa, Turkey. sgurun@uludag.edu.t
Mine Sibel
MS
Gurun
Renee
R
Parker
James C
JC
Eisenach
Michelle
M
Vincler
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002351:Carrageenan; D003566:Cytidine Diphosphate Choline / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007267:Injections; D008297:Male; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000700:Analgesics; D000893:Anti-Inflammatory Agents; C579165:Chrna7 protein, rat; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D014409:Tumor Necrosis Factor-alpha; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D003566:Cytidine Diphosphate Choline; D002351:Carrageenan; D000157:Aconitine