Delayed L-DOPA-induced hyperalgesia.
Previously we reported on L-DOPA's antinociceptive effect on substance P-induced nociceptive behaviors in mice [Shimizu T, Iwata S, Morioka H, Masuyama T, Fukuda T, Nomoto M. Antinociceptive mechanism of L-DOPA. Pain 2004;110;246-9.]. Since significant hyperalgesia was noted following antinociception, our study was designed to investigate the mechanism of this hyperalgesia. Nociceptive behaviors were enhanced 2 h after L-DOPA administration. L-DOPA induced hyperalgesia occurred after conversion to dopamine because co-administration of benserazide, a DOPA decarboxylase inhibitor, completely abolished the L-DOPA-induced hyperalgesia. The D2 receptor agonist, quinpirole, depressed these behaviors entirely, while the D1 antagonist, SCH23390, inhibited the enhancement of these behaviors by L-DOPA. The D2 receptor antagonist, sulpiride, which induced hyperalgesia of the substance P-induced behaviors in naive mice, did not have any effects on L-DOPA-induced hyperalgesia. Spinal cord dopamine content increased rapidly after L-DOPA administration, exhibiting levels 100 times greater than baseline, and then returned to control after 1 h. These results suggested that the dopaminergic inhibitory system for pain sensation was temporarily impaired by excess amounts of exogenous dopamine that were derived from L-DOPA and both D1 and D2 receptors were involved in L-DOPA-induced hyperalgesia.
Shimizu
T
T
Department of Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan.
Iwata
S
S
Miyata
A
A
Fukuda
T
T
Nomoto
M
M
D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced*; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D051379:Mice; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000502:physiology
D001552:Benzazepines; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D007980:Levodopa; D001545:Benserazide; C071262:SK&F 82958