Periaqueductal gray matter dysfunction in migraine: Cause or the burden ofillness?

Objective.-The periaqueductal gray matter (PAG) is at the center of a power ful descending antinociceptive neuronal network. We studied iron homeostasi s in the PAG as an indicator of function in patients with episodic migraine (EM) between attacks and patients with chronic daily headache (CDH) during headache. High-resolution magnetic resonance techniques were used to map t he transverse relaxation rates R2, R2*, and R2' in the PAG, red nucleus (RN ), and substantia nigra (SN). R2' is a measure of non-heme iron in tissues. Methods.-Seventeen patients diagnosed with EM with and without aura, 17 pat ients diagnosed with CDH and medication overuse, and 17 normal adults (N) w ere imaged with a 3.0-tesia magnetic resonance imaging system. For each sub ject, mean values of the relaxation rates, R2 (1/T2), R2* (1/T2*), and R2' (R2* - R2) were obtained for the PAG, RN, and SN. R2, R2*, and R2' values o f the EM, CDH, and N groups were compared using analysis of variance, Stude nt t test, and correlation analysis. Results-in the PAG, there was a significant increase in mean R2' and R2* va lues in both the EM and CDH groups (P<.05) compared with the N group, but n o significant difference in these values was demonstrated between the EM an d CDH groups, or between those with migraine with or without aura in the EM group. Positive correlations were found for duration of illness with R2' i n the EM and CDH groups. A decrease in mean R2' and R2* values also was obs erved in the RN and SN of the CDH group compared with the N and EM groups ( P<.05), explained best by flow activation due to head pain. Conclusions.-Iron homeostasis in the PAG was selectively, persistently, and progressively impaired in the EM and CDH groups, possibly caused by repeat ed migraine attacks. These results support and emphasize the role of the PA G as a possible "generator" of migraine attacks, potentially by dysfunction al control of the trigeminovascular nociceptive system.