TY - JOUR
T1 - Extracranial activation of ATP-sensitive potassium channels induces vasodilation without nociceptive effects
AU - Al-Karagholi, Mohammad Al-Mahdi
AU - Ghanizada, Hashmat
AU - Hansen, Jakob Moller
AU - Aghazadeh, Sameera
AU - Skovgaard, Lene Theil
AU - Olesen, Jes
AU - Ashina, Messoud
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Introduction: Levcromakalim opens ATP-sensitive potassium channels (KATP channel) and induces head pain in healthy volunteers and migraine headache in migraine patients, but no pain in other parts of the body. KATP channels are expressed in C- and Aδ-fibers, and these channels might directly activate nociceptors and thereby evoke pain in humans. Methods: To assess the local effect of KATP channel opening in trigeminal and extra-trigeminal regions, we performed a crossover, double-blind, placebo-controlled study in healthy volunteers. Participants received intradermal and intramuscular injections of levcromakalim and placebo in the forehead and the forearms. Results: Intradermal and intramuscular injections of levcromakalim did not evoke more pain compared to placebo in the forehead (p > 0.05) and the forearms (p > 0.05). Intradermal injection of levcromakalim caused more flare (p < 0.001), skin temperature increase (p < 0.001), and skin blood flow increase (p < 0.001) compared to placebo in the forehead and the forearms. Conclusion: These findings suggest that it is unlikely that levcromakalim induces head pain by direct activation of peripheral neurons.
AB - Introduction: Levcromakalim opens ATP-sensitive potassium channels (KATP channel) and induces head pain in healthy volunteers and migraine headache in migraine patients, but no pain in other parts of the body. KATP channels are expressed in C- and Aδ-fibers, and these channels might directly activate nociceptors and thereby evoke pain in humans. Methods: To assess the local effect of KATP channel opening in trigeminal and extra-trigeminal regions, we performed a crossover, double-blind, placebo-controlled study in healthy volunteers. Participants received intradermal and intramuscular injections of levcromakalim and placebo in the forehead and the forearms. Results: Intradermal and intramuscular injections of levcromakalim did not evoke more pain compared to placebo in the forehead (p > 0.05) and the forearms (p > 0.05). Intradermal injection of levcromakalim caused more flare (p < 0.001), skin temperature increase (p < 0.001), and skin blood flow increase (p < 0.001) compared to placebo in the forehead and the forearms. Conclusion: These findings suggest that it is unlikely that levcromakalim induces head pain by direct activation of peripheral neurons.
KW - K-ATP channel
KW - levcromakalim
KW - pain
KW - nociception
KW - intradermal injection
KW - intramuscular injection
U2 - 10.1177/0333102419888490
DO - 10.1177/0333102419888490
M3 - Journal article
C2 - 31696739
SN - 0333-1024
JO - Cephalalgia
JF - Cephalalgia
ER -