Electron Microscopic and Proteomic Comparison of Terminal Branches of the Trigeminal Nerve in Patients with and without Migraine Headaches.

November, 2014

BACKGROUND: The purpose of this study was to compare the ultrastructural appearance and protein expression of the zygomaticotemporal branch of the trigeminal nerve in patients with and without migraine headaches.

METHODS: After confirmation of migraine headache diagnosis on 15 patients, a 5-mm segment of the zygomaticotemporal branch of the trigeminal nerve that is routinely removed during migraine surgery was compared to similarly sized nerve segments obtained from 15 control patients without a history of migraine headaches, who underwent an endoscopic forehead lift where this nerve is routinely transected. The segments were snap-frozen at -80°C for the downstream proteomics analysis. In addition, the cytoarchitectural differences of the nerve segments obtained from the 15 migraine and 15 control subjects were examined in detail under the electron microscope.

RESULTS: Analysis of liquid chromatography/tandem mass spectrometry data sets identified differentially expressed proteins and networks composed of highly connected molecular modules (p = 10 and p = 10) in patients with migraine headaches. The nerves from patients with migraine headaches had a linear organization, disrupted myelin sheaths and target axons, and discontinuous neurofilaments that were poorly registered with the discontinuous myelin sheaths, suggesting axonal abnormality.

CONCLUSIONS: This study offers electron microscopic and proteomic evidence of axonal abnormality and deregulation of the myelination process in patients with migraine headaches compared with controls, offering the first objective evidence to support the role of peripheral mechanisms in the migraine headache cascade and an explanation as to why the surgical treatment of migraine headaches is efficacious.

Fig. 1. Comparison of the organization of myelin sheaths and axons in control- and migraine-derived nerves. (Above) Longitudinal sections through control-derived nerves. Low-magnification images labeled with antibodies to myelin basic protein (MBP) (above, left), neurofilaments (above, center), and the merged image (above, right). Myelin sheaths and their associated axons are uniformly distributed throughout the nerve, and the nerve demonstrates a characteristic wavy organization. (Center) Higher magnification images showing the close juxtaposition of myelin sheaths labeled with myelin basic protein (center, left) and their axons labeled with neurofilament (center, center). (Center, right) Merged image. (Center) Longitudinal sections through a migraine-derived nerve labeled with antibodies to myelin basic protein (above, left and center, left), neurofilaments (above, center and center, center), and the merged image (above, right and center, right). Note that in contrast to control nerves, the nerve has a less wavy appearance, the myelin sheaths are more pronounced, and the neurofilament labeling is discontinuous along the length of the axon. Regions of intense neurofilament staining are interspersed with a lack of neurofilament staining. (Below) An additional example of a migraine-derived nerve showing the disorganization of myelin sheaths, the lack of continuity of neurofilament expression, and the lack of tight correlation between myelin basic protein labeling and neurofilaments.

Results from: Guyuron B, Yohannes E, Miller R, Chim H, Reed D, Chance MR. Plast Reconstr Surg. 2014 Nov;134(5):796e-805e. doi: 10.1097/PRS.0000000000000696.