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Effect of topical administration of l ‐arginine on formalin‐induced nociception in the mouse: a dual role of peripherally formed NO in pain modulation
Author(s) -
Kawabata Atsufumi,
Manabe Sachiko,
Manabe Yuki,
Takagi Hiroshi
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13108.x
Subject(s) - nociception , microgram , pharmacology , chemistry , arginine , medicine , in vitro , biochemistry , receptor , amino acid
1 We investigated the effects of intraplantar (i.pl.) administration of l ‐arginine and N G ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME) on formalin‐induced behavioural nociception in the mouse. 2 l ‐ but not d ‐arginine, at 0.1 − 1 μg per paw, coadministered with i.pl. formalin, enhanced the second‐but not the first‐phase nociceptive responses, whereas it was without significant effects at 3 μg per paw, and conversely, produced antinociception at 10 μg per paw, resulting in a bell‐shaped dose‐response curve. 3 l ‐NAME at 0.1 − 1 μg per paw, when administered i.pl., exhibited antinociceptive activity in the second phase in a dose‐dependent manner, although its d ‐enantiomer produced no effect. 4 An antinociceptive dose (1 μg per paw) of l ‐NAME (i.pl.) considerably reduced the increase in second‐phase nociception elicited by low doses (1 μg per paw) of i.pl. l ‐arginine. The second‐phase nociception decrease induced by a large dose (10 μg per paw) of i.pl. l ‐arginine was markedly reversed by i.pl. l ‐NAME at 0.1 μg per paw, raising it to a level above that of the control (formalin only). 5 These results suggest that peripheral NO plays a dual role in nociceptive modulation, depending on the tissue level, inducing either nociceptive or antinociceptive responses.