Attenuation by butalbital of capsaicin-induced c-fos-like immunoreactivity in trigeminal nucleus caudalis.
We examined the effects of butalbital (30, 100, and 1000 micrograms/kg) on the number of cells expressing c-fos-like immunoreactivity (c-fos-LI), a marker of neuronal activation, within lamina I, IIo of the trigeminal nucleus caudalis and the nucleus of the solitary tract 2 hours after the intracisternal injection of capsaicin (0.1 mL; 15.25 mg/mL) or vehicle in urethane-anesthetized guinea pigs (N = 45). Robust c-fos-LI was observed within nuclei of cells in the trigeminal nucleus caudalis after capsaicin (329 +/- 35). Butalbital dose-dependently reduced the number of labeled cells to a maximum of 66% (1000 micrograms/kg intraperitoneally [i.p.], P < .01) in lamina I, IIo but not within area postrema, medial reticular nucleus, or the nucleus of the solitary tract. Pretreatment with bicuculline (30 micrograms/kg i.p.) blocked the effect of butalbital, thereby suggesting the importance of the GABAA receptor to activation involved in the transmission of nociceptive information. Our studies suggest the possibility that GABAA receptors might provide an important therapeutic target in migraine and related headache disorders.
Departments of Neurology and Neurosurgery, Massachusetts General Hospital, 149 13th Street, CNY 6403, Charlestown, MA 02129, USA.
F M
FM
Cutrer
D D
DD
Mitsikostas
G
G
Ayata
M
M
Sanchez del Rio
D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014275:Trigeminal Caudal Nucleus / Q000378:metabolism*
D001463:Barbiturates; D016760:Proto-Oncogene Proteins c-fos; C004470:butalbital; D002211:Capsaicin