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.
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Headache Medicine, v.2, n.2, p.41-45, Apr./May/Jun. 2011