Two TRPV1 receptor antagonists are effective in two different experimental models of migraine
Standard
Two TRPV1 receptor antagonists are effective in two different experimental models of migraine. / Meents, Jannis E; Hoffmann, Jan; Chaplan, Sandra R; Neeb, Lars; Schuh-Hofer, Sigrid; Wickenden, Alan; Reuter, Uwe.
in: J HEADACHE PAIN, Jahrgang 16, 24.06.2015, S. Art. 57.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Two TRPV1 receptor antagonists are effective in two different experimental models of migraine
AU - Meents, Jannis E
AU - Hoffmann, Jan
AU - Chaplan, Sandra R
AU - Neeb, Lars
AU - Schuh-Hofer, Sigrid
AU - Wickenden, Alan
AU - Reuter, Uwe
PY - 2015/6/24
Y1 - 2015/6/24
N2 - BACKGROUND: The capsaicin and heat responsive ion channel TRPV1 is expressed on trigeminal nociceptive neurons and has been implicated in the pathophysiology of migraine attacks. Here we investigate the efficacy of two TRPV1 channel antagonists in blocking trigeminal activation using two in vivo models of migraine.METHODS: Male Sprague-Dawley rats were used to study the effects of the TRPV1 antagonists JNJ-38893777 and JNJ-17203212 on trigeminal activation. Expression of the immediate early gene c-fos was measured following intracisternal application of inflammatory soup. In a second model, CGRP release into the external jugular vein was determined following injection of capsaicin into the carotid artery.RESULTS: Inflammatory up-regulation of c-fos in the trigeminal brain stem complex was dose-dependently and significantly reduced by both TRPV1 antagonists. Capsaicin-induced CGRP release was attenuated by JNJ-38893777 only in higher dosage. JNJ-17203212 was effective in all doses and fully abolished CGRP release in a time and dose-dependent manner.CONCLUSION: Our results describe two TRPV1 antagonists that are effective in two in vivo models of migraine. These results suggest that TRPV1 may play a role in the pathophysiological mechanisms, which are relevant to migraine.
AB - BACKGROUND: The capsaicin and heat responsive ion channel TRPV1 is expressed on trigeminal nociceptive neurons and has been implicated in the pathophysiology of migraine attacks. Here we investigate the efficacy of two TRPV1 channel antagonists in blocking trigeminal activation using two in vivo models of migraine.METHODS: Male Sprague-Dawley rats were used to study the effects of the TRPV1 antagonists JNJ-38893777 and JNJ-17203212 on trigeminal activation. Expression of the immediate early gene c-fos was measured following intracisternal application of inflammatory soup. In a second model, CGRP release into the external jugular vein was determined following injection of capsaicin into the carotid artery.RESULTS: Inflammatory up-regulation of c-fos in the trigeminal brain stem complex was dose-dependently and significantly reduced by both TRPV1 antagonists. Capsaicin-induced CGRP release was attenuated by JNJ-38893777 only in higher dosage. JNJ-17203212 was effective in all doses and fully abolished CGRP release in a time and dose-dependent manner.CONCLUSION: Our results describe two TRPV1 antagonists that are effective in two in vivo models of migraine. These results suggest that TRPV1 may play a role in the pathophysiological mechanisms, which are relevant to migraine.
U2 - 10.1186/s10194-015-0539-z
DO - 10.1186/s10194-015-0539-z
M3 - SCORING: Journal article
C2 - 26109436
VL - 16
SP - Art. 57
JO - J HEADACHE PAIN
JF - J HEADACHE PAIN
SN - 1129-2369
ER -