Decreased Plasma Methionine-Enkephalin Levels in Cluster Headache Patients

作者：Mosnaim Aron D^*; Maturana Patricio; Puente Javier; Wolf Marion E

来源：American Journal of Therapeutics, 2012, 19(3): 174-179.

DOI：10.1097/MJT.0b013e3182456a61

• methionine-enkephalin plasma levels
• cluster headache
• migraine headache
• longitudinal studies
• enkephalins and pain modulation
• aminopeptidase inhibitors

Results from a longitudinal study (blood drawn at days 29, 64, 89,124, 142, and 182 of the protocol) shows that the concentration of platelet-poor plasma (PPP) methionine(5)-enkephalin (MET) in healthy, drug-free, white male individuals (n = 5) remains within a relatively narrow range, well within the experimental error of the analytical procedures used. Interindividual differences fail to reach statistical significance [x +/- SD and range (MET picograms per mL of PPP) of 91.2 +/- 15.1, 67.1 +/- 113.5; 69.6 +/- 7.5, 66.1-90.1; 76.6 +/- 12.6, 58.5-93.1; 86.8 +/- 10.9, 76.3-107.4; and 84.5 +/- 11.4, 68.9-103.4; for subjects 1-5, respectively]. MET levels were similar to those recorded from single samples obtained from a group of 24 white male, age-comparable, drug-free healthy volunteers [x +/- 6 SD and range (picograms of MET per mL of PPP) of 83.3 +/- 15.1 and 57.4-119.1]. The controls%26apos; range for all the subjects (n = 29) was 57.4-119.1 pgMET/mL PPP. Compared with the controls, individual patients with cluster headache (CH) show a much wider variation in PPP MET levels (blood drawn at different time intervals, at least 10 samples per patient, over a period of 221-298 days), with many (slightly over half) of single values below the controls range; no single MET level was above the controls range [x +/- SD and range (picograms of MET per mL of PPP) of 56.4 +/- 27.7, 6.1-100.5; 72.6 +/- 20.5, 43.0-113.0; 46.0 +/- 28.5, 10.0-92.6; 53.6 +/- 27.5, 13.0-101.0; 52.0 +/- 26.1, 17.5-83.6; 63.5 +/- 22.3, 21.7-91.3 for individuals A-F, respectively]. Although interindividual differences within the patients%26apos; group were not statistically significant, their peptide levels were significantly lower than those of controls. Neither the presence of unspecified %26quot;headaches between clinic visits%26apos;%26apos; and %26quot;daily headaches%26quot; (patients E and F, respectively), nor the use of a number of drugs known to lack inhibitory activity upon the aminopeptidase-MET degradation reaction, seemed to significantly influence MET concentration. The results could lead to a better understanding of the etiology of the pain associated with CH, with the relative changes in plasma peptide perhaps reflecting the patients%26apos; vulnerability to such a condition. Pharmacological modulation of MET function may prove useful in the treatment of CH-associated pain, whether the development of such drugs could find useful pharmacological applications remains to be explored.

• 出版日期2012-5