TY - JOUR

T1 - Involvement of adenosine signaling pathway in migraine pathophysiology

T2 - a systematic review of preclinical studies

AU - Thuraiaiyah, Janu

AU - Kokoti, Lili

AU - Al-Karagholi, Mohammad Al-Mahdi

AU - Ashina, Messoud

PY - 2022

Y1 - 2022

N2 - Background Adenosine is a purinergic signaling molecule with a wide range of physiological functions including anti- and pronociceptive properties. Adenosine receptors are expressed in the trigeminovascular system, and adenosine receptor antagonist, caffeine, relieves migraine headache. We performed a systematic review of the literature of preclinical data addressing the role of adenosine in migraine pathophysiology. Methods PubMed and EMBASE were searched for pre-clinical studies on the role of adenosine in migraine pathophysiology on September 5(th), 2021. Results A total of 2510 studies were screened by title and abstract. Of these, thirteen pre-clinical studies evaluating adenosine, adenosine A1, A2A and A3 receptors were included. These studies showed that adenosine signaling pathway is involved in controlling vascular tone. Furthermore, electrical stimulation of the trigeminal ganglion modulates the expression of adenosine A(1) and A(2A) receptors in the trigeminal ganglion and trigeminal nucleus caudalis implicating adenosine signaling pathway in pain transmission. Conclusion Preclinical studies showed that adenosine has a dual effect on vasodilation and trigeminal pain pathway due to different receptor activation, suggesting a possible role of adenosine in migraine pathophysiology. Studies investigating pharmacological characteristics of subtypes of adenosine receptors are needed to further elucidate their role as a potential target for migraine treatment.

AB - Background Adenosine is a purinergic signaling molecule with a wide range of physiological functions including anti- and pronociceptive properties. Adenosine receptors are expressed in the trigeminovascular system, and adenosine receptor antagonist, caffeine, relieves migraine headache. We performed a systematic review of the literature of preclinical data addressing the role of adenosine in migraine pathophysiology. Methods PubMed and EMBASE were searched for pre-clinical studies on the role of adenosine in migraine pathophysiology on September 5(th), 2021. Results A total of 2510 studies were screened by title and abstract. Of these, thirteen pre-clinical studies evaluating adenosine, adenosine A1, A2A and A3 receptors were included. These studies showed that adenosine signaling pathway is involved in controlling vascular tone. Furthermore, electrical stimulation of the trigeminal ganglion modulates the expression of adenosine A(1) and A(2A) receptors in the trigeminal ganglion and trigeminal nucleus caudalis implicating adenosine signaling pathway in pain transmission. Conclusion Preclinical studies showed that adenosine has a dual effect on vasodilation and trigeminal pain pathway due to different receptor activation, suggesting a possible role of adenosine in migraine pathophysiology. Studies investigating pharmacological characteristics of subtypes of adenosine receptors are needed to further elucidate their role as a potential target for migraine treatment.

KW - Headache

KW - Adenosine receptor

KW - Pre-clinical

KW - Pain

KW - RECEPTOR AGONIST GR79236

KW - SENSITIVE K+ CHANNELS

KW - ADENOSINE-A1-RECEPTOR AGONIST

KW - PEPTIDE RELEASE

KW - ANTAGONIST

KW - PHARMACOLOGY

KW - STIMULATION

U2 - 10.1186/s10194-022-01412-0

DO - 10.1186/s10194-022-01412-0

M3 - Review

C2 - 35382738

VL - 23

JO - Journal of Headache and Pain

JF - Journal of Headache and Pain

SN - 1129-2369

M1 - 43

ER -