Circadian-rhythm-dependent effects of L-N-G-nitroarginine methyl ester (L-NAME) on morphine-induced analgesia

Guney H., Gorgun C., Tunctan B., Uludag O., Hodoglugil U., Abacioglu N., ...More

CHRONOBIOLOGY INTERNATIONAL, vol.15, no.3, pp.283-289, 1998 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 15 Issue: 3
  • Publication Date: 1998
  • Doi Number: 10.3109/07420529808998690
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.283-289
  • Gazi University Affiliated: Yes


Circadian changes in the interactions between L-N-G-nitroarginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, and morphine-induced antinociception were investigated by the mouse hot-plate test. Both the basal pain sensitivity and morphine-induced analgesia undergo significant 24h variations. L-NAME (40 mg/kg, ip) alone did not show any antinociceptive activity, but potentiated morphine-induced analgesia when combined with morphine at all injection times. In terms of percentage absolute potentiation (%AP), L-NAME dramatically augmented the analgesic effect of morphine in the late dark period at 19 hours after lights on (HALO). It is concluded that nitric oxide (NO) is involved in the modulation of the analgesic effect of morphine; thus, the L-NAME and morphine combination might be beneficial in alleviating pain.