Research funded by the Facial Pain Research Foundation provides insights into the role of brain inflammation in patients with Trigeminal Neuralgia
Jerry Krbec MBA, FPRF Trustee
At the last Society for Neuroscience Annual Meeting, research conducted by professors John Neubert and Mingzhou Ding and their colleagues, supported by the Facial Pain Research Foundation was presented. The name of the presentation was “Free Water as a Neural Marker of Trigeminal Neuralgia”. This research was part of the FPRF focus on identifying pain pathways in TN.
Imaging free water is a new methodology based upon diffusion MRI. Measuring the level of free water between cells in brain structures indicates the level of neuroinflammation present in those structures. The role that inflammation plays in TN is currently being hotly debated, so this was very topical and timely research.
Previous analysis done by the team had shown that of all the brain white matter structures imaged for free water in TN patients, the pontine crossing tract (PCT), which is a white matte tract close to the trigeminal nuclei, showed particular sensitivity to TN-related neuroinflammation. The PCT connects signals from the brainstem to the cerebellum and may also include part of the tract that links the trigeminal nerve to the thalamus. The thalamus is the area of the brain that routes most pain signals, including TN pain, to higher brain levels where pain is actually perceived. They imaged 27 patients that had TN1 or TN2 with and without surgical treatment.
In the TN1 non-surgical group, the level of inflammation correlated very tightly to the length of disease duration in these patients. (See Fig. 2.) This means that the longer a patient had TN, the more inflammation was present in their PCT. In the TN1 patients with prior surgery, there were still high levels of inflammation measured but the amount of inflammation no longer correlated with disease duration. For some reason surgery seems to not decrease the inflammation present, but it does disturb the relationship between neuroinflammation and disease progression.
In TN2 patients with or without surgery there was no statistically significant relationship between disease duration and inflammation, suggesting that there is a difference in the cause of the two conditions. (See Fig. 3.)
This study has revealed much about the role of inflammation in the brains of TN patients. We have learned that in the brain white matter of TN patients, the only location with significant inflammation present is the pontine crossing tract (PCT). The PCT is in the same area that gives rise to the trigeminal nerve, and from where trigeminal pain signals are transmitted to the higher levels of the brain. Inflammation anywhere in the body normally causes pain so this obviously provides researchers with a new target area to direct therapies towards.
It was also found that the amount of inflammation in the brain of TN1 patients increases the longer they have had the disease which may indicate some sort of cumulative impact or progression of the disease over time. The finding that this same relationship over time doesn’t hold true in TN2 patients or patients that have had surgery makes the issue of inflammation and disease progression more difficult to understand. The data maybe providing more conformation that there are differences in the mechanisms causing TN1 and TN2 pain which may be why the progression relationship is lost. While more research is needed to unravel what is occurring, this study also validated the usefulness of using the measurement of free water levels to tract the inflammation that is present in the brain.