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5‐HT 2A Receptor Activation and Nitric Oxide Synthesis: A Possible Mechanism Determining Migraine Attacks
Author(s) -
Srikiatkhachorn Anan,
Suwattanasophon Chalalai,
Ruangpattanatawee Unchalee,
PhansuwanPujito Pansiri
Publication year - 2002
Publication title -
headache: the journal of head and face pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.14
H-Index - 119
eISSN - 1526-4610
pISSN - 0017-8748
DOI - 10.1046/j.1526-4610.2002.02142.x
Subject(s) - nociception , spinal trigeminal nucleus , agonist , medicine , migraine , endocrinology , nitric oxide , ketanserin , nitric oxide synthase , anesthesia , chemistry , cortical spreading depression , receptor , vasodilation , trigeminal nerve , central nervous system , 5 ht receptor , serotonin
Objective .—To determine the effect of the 5‐HT 2A receptor in control of spinal nociception, cerebral circulation, and nitric oxide synthase (nNOS) expression in trigeminovascular neurons. Background .—The plasticity of the 5‐HT 2A receptor is a possible factor determining the course of migraine. Up‐regulation of this receptor has been demonstrated to correlate with the increasing frequency of migraine attacks and may underlie the development of chronic daily headache. Methods .—Adult male Wistar rats were divided into groups receiving the 5‐HT 2A agonist, 1,2,5‐dimethoxy‐4‐iodophenyl‐2‐aminopropane (DOI), nitroglycerin, or normal saline. The tail flick test and chemical nociception‐evoked Fos‐expression in dorsal horn neurons were used as indicators of nociception. Regional cerebral blood flow was monitored using laser Doppler flowmetry. Expression of Fos and nNOS was studied using immunohistochemical method. Results .—Administration of DOI led to the shortening of tail flick latency (1.3 ± 0.2 and 7.2 ± 0.6 seconds for DOI‐treated and control groups, respectively). The number of Fos‐immunoreactive neurons was also greater in the DOI‐treated group compared with the control group. DOI also produced long‐lasting cerebral hyperemia (123% of baseline value) associated with the enlargement of perivascular nNOS‐immunoreactive nerve fibers and increased nNOS‐immunoreactive neurons in trigeminal ganglia and trigeminal nucleus caudalis. These findings resembled those observed in the rats exposed to nitroglycerin. Conclusion .—Our results suggest that activation of the 5‐HT 2A receptor leads to an enhancement of NO production in trigeminovascular pathway. NO may trigger migraine attacks by inducing cerebral vasodilation and sensitizing the perivascular nociceptors and central nociceptive neurons in trigeminovascular system. Up‐regulation of this pronociceptive receptor can increase headache attacks and contributes to the development of chronic daily headache.