SUMATRIPTAN CAN INHIBIT TRIGEMINAL AFFERENTS BY AN EXCLUSIVELY NEURALMECHANISM

Mechanical distortion of the human cranial venous sinuses. is painful as is cranial venous sinus distension during migraine. Sumatriptan, th e serotonin (5HT)(1B/D)-like receptor agonist, is highly effective in relieving migraine headache and part of its action may be due to const riction of cranial dural blood vessels. Using immunohistochemical dete ction of the immediate early gene Fos, we have mapped the spatial patt ern of neural activation in the caudal medulla and the upper cervical spinal cord (CI, C2 and C3) in cats following either electrical or mec hanical stimulation of the superior sagittal sinus. Fourteen cats were anaesthetized with alpha-chloralose and prepared for physiological mo nitoring of blood pressure, heart rate, rectal temperature and expired CO2. Electrical stimulation evoked significant increases in the (medi an) numbers of Fos-positive cells in laminae I and IIo of the superfic ial dorsal horn of CI, C2 and C3 cervical spinal cord (88, 92 and 18 c ells, respectively) and of the trigeminal nucleus caudalis (TNC) (81 c ells). Mechanical stimulation revealed a similar pattern of neural act ivation but with reduced intensity in laminae I and Ilo of the TNC (38 cells) and of CI and C2 (32 and 31 cells, respectively). The temporal is muscle was stimulated mechanically in the control group and the num bers and distribution of Fos-positive cells were no different from tho se in non-stimulated controls. Treatment with sumatriptan reduced the numbers of Fos-positive cells found in laminae I and Ilo of the TNC an d C2 (6, 13 cells and 9 cells, respectively) after mechanical stimulat ion. These data suggest that the neural effect of sumatriptan alone is sufficient for significant attenuation of transmission in the trigemi nal system. The fact that sumatriptan can inhibit trigeminal activatio n without its vascular effects suggests that drugs without a significa nt activity on blood vessels may be effective in the treatment of migr aine.