Attenuation by butalbital of capsaicin-induced C-fos-like immunoreactivity in trigeminal nucleus caudalis

We examined the effects of butalbital (30, 100, and 1000 μg/kg) on the number of cells expressing c-fos-like immunoreactivity (c-fos-LI), a marker of neuronal activation, within lamina I, II(o) 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 μg/kg intraperitoneally [IP], P<.01) in lamina I, II(o) but not within area postrema, medial reticular nucleus, or the nucleus of the solitary tract. Pretreatment with bicuculline (30 μg/kg IP) blocked the effect of butalbital, thereby suggesting the importance of the GABA(A) receptor to activation involved in the transmission of nociceptive information. Our studies suggest the possibility that GABA(A) receptors might provide an important therapeutic target in migraine and related headache disorders.