title: Triptans attenuate capsaicin-induced CREB phosphorylation within the trigeminal nucleus caudalis: a mechanism to prevent central sensitization?
abstract: The c-AMP-responsive element binding protein (CREB) and its phosphorylated product (P-CREB) are nuclear proteins expressed after stimulation of pain-producing areas of the spinal cord. There is evidence indicating that central sensitization within dorsal horn neurons is dependent on P-CREB transcriptional regulation. The objectives of the study were to investigate the expression of P-CREB in cells in rat trigeminal nucleus caudalis after noxious stimulation and to determine whether pre-treatment with specific anti-migraine agents modulate this expression. CREB and P-CREB labelling was investigated within the trigeminal caudalis by immunohistochemistry after capsaicin stimulation. Subsequently, the effect of i.v. pre-treatment with either sumatriptan (n = 5), or naratriptan (n = 7) on P-CREB expression was studied. Five animals pre-treated with i.v. normal saline were served as controls. CREB and P-CREB labelling was robust in all animal groups within Sp5C. Both naratriptan and sumatriptan decreased P-CREB expression (p = 0.0003 and 0.0013) within the Sp5C. Triptans attenuate activation of CREB within the central parts of the trigeminal system, thereby leading to potential inhibition of central sensitization. P-CREB may serve as a new marker for post-synaptic neuronal activation within Sp5C in animal models relevant to migraine.
authors.affiliation: Headache Group, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. dmitsikostas@ath.forthnet.gr
authors.forename: Dimos D
authors.initials: DD
authors.lastname: Mitsikostas
authors.forename: Yolande E
authors.initials: YE
authors.lastname: Knight
authors.forename: Michele
authors.initials: M
authors.lastname: Lasalandra
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kavantzas
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goadsby
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000633:toxicity; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects* / Q000378:metabolism*; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D010146:Pain / Q000378:metabolism; D010766:Phosphorylation; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000633:toxicity; D018170:Sumatriptan / Q000494:pharmacology; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects* / Q000378:metabolism*; D014363:Tryptamines / Q000494:pharmacology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D010880:Piperidines; D018689:Sensory System Agents; D014363:Tryptamines; D018170:Sumatriptan; C106783:naratriptan; D002211:Capsaicin