2002 Wolff Award. 5 -HT2A receptor activation and nitric oxide synthesis: a possible mechanism determining migraine attacks.
OBJECTIVE
To determine the effect of the 5-HT2A receptor in control of spinal nociception, cerebral circulation, and nitric oxide synthase (nNOS) expression in trigeminovascular neurons.


BACKGROUND
The plasticity of the 5-HT2A 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-HT2A 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.


CONCLUSIONS
Our results suggest that activation of the 5-HT2A 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.
Srikiatkhachorn
Anan
A
Department of Physiology, King Chulalongkorn Memorial Hospital and Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
Suwattanasophon
Chalalai
C
Ruangpattanatawee
Unchalee
U
Phansuwan-Pujito
Pansiri
P
D000818:Animals; D002560:Cerebrovascular Circulation / Q000502:physiology; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D009619:Nociceptors / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*
D011985:Receptors, Serotonin; D009569:Nitric Oxide