Tuberoinfundibular Dopaminergic Transmission in Children Migraine

I n 1977 S i c u t e r i i d e n t i f i e d i n dopamine t h e s e c o n d n e u r o t r a n s m i t t e r i n v o l v e d i n m i g r a i n e p a t h o g e n e s i s . T h i s h y p o t h e s i s was s u p p o r t e d by c l i n i c a l aiid c l i n i c a l p h a r m a c o l o g i c a l o b s e r v a t i o n s ' . P r o l a c t i o n ( P R L ) , t h e hormone s e c r e t e d by d i s t i n c t a c i d o p h i l c e l l s of t h e a n t e r i o r p i t u i t a r y g l a n d 2 , h a s been u s e d a s a n i n d e x i n t h e s t u d y of tlie dop a r n i n e r g i c f u n c t i o n i n migrairie3. I n f a c t , PRL re lease from mammotroph c e l l s o f t h e p i t u i t a r y g l a n d is u n d e r i n h i b i t o r y c o n t r o l of t h e d o p e m i n e r g i c i n f u n d i b u l a r h y p o t h a l a m i c s y s t e m ( T 1 D A l 4 . Dopamine, r e l e a s e d by T I D A s y s t e m thrw&i p o r t a l r e t r o g r a d e c i r c u l a t i o n , r e a c h e s t h e niamriiotroph c e l l s where i ts i n h i b i t o r y a c t i c n d e v e l o p s 5 . T h i s a c t i o n is inodu la t ed by hormones s u c h a s es t rog e n s a n d t h y r o t r o p i n r e l e a s i n g hormone ( T R H 16. I t h a s been s u g g e s t e d t h a t m i g r a i n e p a t h o l o g y nay be c h a r a c t e r i z e d by t h e oc c u r r e r i c e of d o p a m i n e r g i c r e c e p t o r s u p e r s e n s i t i v i t y due t o r e d u c e d s y n t h e s i s of t h e n e u r ~ t r a n s m i t t e r ~ . ~ ~ ~ . T h i s of d r u g s c a p a b l e of a f f e c t i n g t h e a c t i v i t y of t h e t u b e r o i n f u n d i b o l a r dopamin e r g i c s y s t e m ( T I D A ) , e i t h e r a t p r e or p o s t s y n a p t i c l e v e l , e.g. 1-DOPA, nom i f e n s i n e , s u l p i r i d e and l i s u r i d e . I t r e m a i n s c o n t r o v e r s i a l w h e t h e r h i g h p l a s m a e s t r o g e n c o n c e n t r a t i o n s may fac i l i t a t e t h i s anomalylQ*ll . I n f a c t , t h e y m o d u l a t e t h e r e c e p t o r i a l s e n s i t i v i t y l 2 r l3 and a c t i v i t y of mono-aminoxydase ( M A O ) and dvFeiiiir,t-.R--t13dI'oxylhsti ( E F l i ) enzyiiies whicli i .egu1at.e dopanlilre s y n t h e s i s and c a t a b o l i s m 1 4 . I t is u~ known w h e t h e r t h e s e a n o m a l i e s p r o v e e v i d e n t i n c h i l d r e n ' s h e a d a c h e , a patl i6logic coricli t ivri i n which t h e i n t e r f e r e n c e of s e x u a l horaiones are t o b e consL d e r e d i n s i g n i f j carit''. The airli of t h i s work was t o tes t p r o l a c t i n ylasri,;, l e v e l s i r , ti g ~ ~ ? i l ? of mig r a i n o u s c h i l d r e n , i n h e a d a c h e f r e e p e r i o d s , a f t e r acjii8.i n i s t r a t i o n o f p l a c e b o and d o p a m i n e a g o n i s t d r u g s , known t o a f f e c t t h e a c t i v i t y of T I D A . biATEnIALS A N G METHODS a ) P a t i e n t s and c o n t r o l s The c h i l d r e n ( f i v e males, f i v e females), a l l a f f e c t e d by common m i g r a i n e were examined t o d e t e r m i n e p r o l a c t i n p l a sma l e v e l s bef0r .e and a f t e r pha rmaco log i c a l tests. The d i a g n o s i s was made a c c o r d i r i g t o t h e c r i t e r i a d e f i n e d by t h e "Ad hoc Committee o n C l a s s i f i c a t i o n of headache"16. The r a n g e of age was 6 t o 10 y e a r s ( T a b l e 1 ) . The case h i s t o r y of e a c h p a t i e n t i n d i c a t e d t h e o c c u r r e n c e of m i g r a i n e a t t a c k s for a t l eas t o n e y e a r and a f r e q u e n c y of two-four a t t a c k s p e r rrionth. A l l c h i l d r e n showed p o s i t i v e m i g r a i n e f a m i l y h i s t o r y . The n e u r o l o g i c a l e x a m i n a t i o n a n d conimon r o u t i n e l a b o r a t o r y t iematochemical tes ts were norma l i n a l l s u b j e c t s . When a d m i t t e d t o t h e p r e s e n t s t u d y , c h i l d r e n d i d ' n t s u f f e r m i g r a i n e a t t a c k i n t h e p r e v i o u s s e v e n d a y s a n d d u r i n g t h e same p e r i o d t h e y had n o t t a k e n any m e d i c a t i o n . The c o n t r o l g r o u p c o n s i s t e d of c h i l d r e n ma tched fo r age and sex w i t h p a t i m t s . In fo rmed c o n s e n t was o b t a i n e d a f t e r n a t u r e o f t h e p r o c e d u r e had b e e n f u l l y e x p l a i n e d t o t h e c h i l d r e n ' s p a r e n t s . b ) b loda l i t y of p r o l a c t i n s t u d y P r o l a c t i n p l a s m a l e v e l s were t e s t e d a t 9 a . m . i n b a s a l c o n d i t i o n s and t h e n -