TY - JOUR
T1 - The NMDA receptor antagonist MK-801 reduces capsaicin-induced c-fos expression within rat trigeminal nucleus caudalis
AU - Mitsikostas, Dimos D.
AU - Sanchez Del Rio, Margarita
AU - Waeber, Christian
AU - Moskowitz, Michael A.
AU - Cutrer, F. Michael
N1 - Funding Information:
The authors are grateful to Masao Sasamata, Ph.D. and Shobu Namura, M.D., Ph.D., for their assistance. This study was supported in part by the Hellenic Navy, General Staff (D.D.M.); by the International Headache Society research fellowship award 1997 (M.S.R.); and by NS 01803 (F.M.C.) and NS 35611 (C.W. and M.A.M.) of the National Institutes of Health.
PY - 1998/5
Y1 - 1998/5
N2 - The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) was examined on c-fos-like immunoreactivity (c- fos-LI) in urethane-anesthetized Sprague-Dawley rats using a polyclonal antibody. C-fos, an indicator of neuronal activation, was assessed within the trigeminal nucleus caudalis (TNC), area postrema, lateral reticular and solitary tract nuclei 2 h after intracisternal injection of capsaicin. C- fos-positive cells were counted at three representative levels corresponding to obex, -2.05 mm and -6.45 mm in 18 tissue sections (50 μm). A weighted average was obtained reflecting total brainstem expression within lamina I, II of TNC using a recently validated method. Capsaicin (0.1, 1, 5, 10 and 15 nmol) caused a dose-dependent labeling of cells in lamina I, II at obex similar to that previously reported after intracisternal blood or carrageenin administration in rats and guinea pigs. MK-801 (0.3, 1 and 3 mg/kg) administered i.p. 30 min before capsaicin (5 nmol in 100 μl artificial CSF) reduced significantly and dose-dependently (12%, 36% and 47%, respectively) the c-fos-LI cells in TNC at each level from rostral to caudal but not in solitary tract, area postrema and lateral reticular nuclei, and for unexplained reasons, increased c-fos-LI within the inferior olive. These results suggest that NMDA receptors provide a potential therapeutic target for cephalic pain (e.g. migraine) due to trigeminovascular activation from meningeal afferents.
AB - The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) was examined on c-fos-like immunoreactivity (c- fos-LI) in urethane-anesthetized Sprague-Dawley rats using a polyclonal antibody. C-fos, an indicator of neuronal activation, was assessed within the trigeminal nucleus caudalis (TNC), area postrema, lateral reticular and solitary tract nuclei 2 h after intracisternal injection of capsaicin. C- fos-positive cells were counted at three representative levels corresponding to obex, -2.05 mm and -6.45 mm in 18 tissue sections (50 μm). A weighted average was obtained reflecting total brainstem expression within lamina I, II of TNC using a recently validated method. Capsaicin (0.1, 1, 5, 10 and 15 nmol) caused a dose-dependent labeling of cells in lamina I, II at obex similar to that previously reported after intracisternal blood or carrageenin administration in rats and guinea pigs. MK-801 (0.3, 1 and 3 mg/kg) administered i.p. 30 min before capsaicin (5 nmol in 100 μl artificial CSF) reduced significantly and dose-dependently (12%, 36% and 47%, respectively) the c-fos-LI cells in TNC at each level from rostral to caudal but not in solitary tract, area postrema and lateral reticular nuclei, and for unexplained reasons, increased c-fos-LI within the inferior olive. These results suggest that NMDA receptors provide a potential therapeutic target for cephalic pain (e.g. migraine) due to trigeminovascular activation from meningeal afferents.
KW - Inferior olive
KW - MK-801
KW - Migraine
KW - N-Methyl-D-aspartate
KW - Pain
KW - Trigeminal nucleus caudalis
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U2 - 10.1016/S0304-3959(98)00051-7
DO - 10.1016/S0304-3959(98)00051-7
M3 - Article
C2 - 9696479
AN - SCOPUS:0031745826
SN - 0304-3959
VL - 76
SP - 239
EP - 248
JO - Pain
JF - Pain
IS - 1-2
ER -