44 Headache Medicine, v.2, n.2, p.41-45, Apr./May/Jun. 2011
PERES MF, VIEIRA DS, MASRUHA MR, GONÇALVES AL, MERCANTE JP, NAFFAH-MAZZACORATTI MG
In contrast, a recent study in combat related
postraumatic stress disorder showed the opposite. CSF
and plasma orexin-A concentrations were significantly
lower in the patients with PTSD as compared with healthy
subjects, as wel as strongly and negatively correlated with
PTSD severity as measured by the Clinician-Administered
PTSD Scale (CAPS) in patients with PTSD.
19
These findings,
in the same direction as our study, suggest a low orexin-A
activity in anxiety.
The hypothalamus is a key region in the brain
regulating important aspects of defense mechanisms and
survival such as pain, sleep-wake cycle, appetite, hormonal
and metabolism balance, reproduction. Although limited
evidence is found in the literature, it is not surprising that
an important defense mechanism such as anxiety might
be regulated in the hypothalamus and possibly in
orexinergic neurons. One can hypothesize orexin could
play a role in regulating anxiety in CM, and migrainous
patients with lowered orexin-A levels could develop anxiety
because orexin is deficient. On the other hand, the excess
of anxiety commonly experienced by CM patients could
lead to a depletion in orexin levels.
Lowered orexin-A levels have been extensively linked
to excessive daytime sleepiness in narcolepsy and other
conditions due to a loss of orexinergic neurons.
24
We have
not found a difference in patients versus controls, nor a
correlation with BMI and EDS in our sample. It is less likely
that a loss in orexinergic neurons happen in this chronic
migraine context.
We could not find a difference between patients and
controls, these could be due to the lack of an adequate
control population, our controls were not absolutely free
of symptoms; they underwent a LP to rule out a
neurological condition and they could have experienced
pain and anxiety during the procedure.
This orexinergic system has been considered as a
potential target for the treatment of sleep disorders, it may
be also a potentially important therapeutic agent for
migraine and anxiety in the future.
We hope to encourage further studies focusing the
orexinergic system and the hypothalamus in migraine and
anxiety.
REFERENCES
1. Eriksson KS, Sergeeva OA, Haas HL, Selbach O. Orexins/
hypocretins and aminergic systems. Acta Physiol (Oxf). 2010;
198(3):263-75.
2. de Lecea L. A decade of hypocretins: past, present and future of the
neurobiology of arousal. Acta Physiol (Oxf). 2010;198(3):203-8.
3. Arias-Carrion O, Bradbury M. The sleep-wake cycle, the
hypocretin/orexin system and narcolepsy: advances from
preclinical research to treatment. CNS Neurol Disord Drug
Targets. 2009;8(4):232-4.
4. Queiroz LP, Peres MF, Piovesan EJ, Kowacs F, Ciciarelli M, Souza
J, et al. A nationwide population-based study of migraine in
Brazil. Cephalalgia. 2009;29(6):642-9.
5. Peres MF, Sanchez del Rio M, Seabra ML, Tufik S, Abucham J,
Cipolla-Neto J, et al. Hypothalamic involvement in chronic
migraine. J Neurol Neurosurg Psychiatry. 2001;71(6):747-51.
6. Rainero I, De Martino P, Pinessi L. Hypocretins and primary
headaches: neurobiology and clinical implications. Expert Rev
Neurother. 2008;8(3):409-16.
7. Holland PR, Akerman S, Goadsby PJ. Modulation of nociceptive
dural input to the trigeminal nucleus caudalis via activation of
the orexin 1 receptor in the rat. Eur J Neurosci. 2006;24
(10):2825-33.
8. Holland PR, Akerman S, Goadsby PJ. Orexin 1 receptor activation
attenuates neurogenic dural vasodilation in an animal model of
trigeminovascular nociception. J Pharmacol Exp Ther. 2005;
315(3):1380-5.
9. Bartsch T, Levy MJ, Knight YE, Goadsby PJ. Differential modulation
of nociceptive dural input to [hypocretin] orexin A and B receptor
activation in the posterior hypothalamic area. Pain. 2004;
109(3):367-78.
10. Rainero I, Rubino E, Valfre W, Gallone S, De Martino P, Zampella
E, et al. Association between the G1246A polymorphism of the
hypocretin receptor 2 gene and cluster headache: a meta-analysis.
J Headache Pain. 2007;8(3):152-6.
11. Pinessi L, Binello E, De Martino P, Gallone S, Gentile S, Rainero
I, et al. The 1246G-->A polymorphism of the HCRTR2 gene is
not associated with migraine. Cephalalgia. 2007; 27 (8):945-
9.
12. Schurks M, Limmroth V, Geissler I, Tessmann G, Savidou I,
Engelbergs J, et al. Association between migraine and the
G1246A polymorphism in the hypocretin receptor 2 gene.
Headache. 2007;47(8):1195-9.
13. Peterlin BL, Rosso AL, Rapoport AM, Scher AI. Obesity and
migraine: the effect of age, gender and adipose tissue
distribution. Headache. 2010;50(1):52-62.
14. Bigal ME. Correlation of increase in phosphene threshold with
reduction of migraine frequency: a comment. Headache. 2009;
49(5):783-4.
15. Peterlin BL, Rapoport AM, Kurth T. Migraine and obesity:
epidemiology, mechanisms, and implications. Headache.
2010;50(4):631-48. Comment in Headache. 2010; 50(4):649.
16. Sarchielli P, Rainero I, Coppola F, Rossi C, Mancini M, Pinessi L,
et al. Involvement of corticotrophin-releasing factor and orexin-
A in chronic migraine and medication-overuse headache: findings
from cerebrospinal fluid. Cephalalgia. 2008;28(7):714-22.
17. Suzuki M, Beuckmann CT, Shikata K, Ogura H, Sawai T. Orexin-
A (hypocretin-1) is possibly involved in generation of anxiety-
like behavior. Brain Res. 2005;1044(1):116-21.
18. Johnson PL, Truitt W, Fitz SD, Minick PE, Dietrich A, Sanghani S,
et al. A key role for orexin in panic anxiety. Nat Med. 2010;
16(1):111-5.