Neurochemical dynamics of acute orofacial pain in the human trigeminal brainstem nuclear complex

Abstract

The trigeminal brainstem sensory nuclear complex is the first central relay structure mediating orofacial somatosensory and nociceptive perception. Animal studies suggest a substantial involvement of neurochemical alterations at such basal CNS levels in acute and chronic pain processing. Translating this animal based knowledge to humans is challenging. Human related examining of brainstem functions are challenged by MR related peculiarities as well as applicability aspects of experimentally standardized paradigms. Based on our experience with an MR compatible human orofacial pain model, the aims of the present study were twofold: 1) from a technical perspective, the evaluation of proton magnetic resonance spectroscopy at 3 T regarding measurement accuracy of neurochemical profiles in this small brainstem nuclear complex and 2) the examination of possible neurochemical alterations induced by an experimental orofacial pain model. Data from 13 healthy volunteers aged 19-46 years were analyzed and revealed high quality spectra with significant reductions in total N-acetylaspartate (N-acetylaspartate + N-acetylaspartylglutamate) (-3.7%, p = 0.009) and GABA (-10.88%, p = 0.041) during the pain condition. These results might reflect contributions of N-acetylaspartate and N-acetylaspartylglutamate in neuronal activity-dependent physiologic processes and/or excitatory neurotransmission, whereas changes in GABA might indicate towards a reduction in tonic GABAergic functioning during nociceptive signaling. Summarized, the present study indicates the applicability of H-MRS to obtain neurochemical dynamics within the human trigeminal brainstem sensory nuclear complex. Further developments are needed to pave the way towards bridging important animal based knowledge with human research to understand the neurochemistry of orofacial nociception and pain.

Alterations in cortical excitability during pain: A combined TMS-EEG Study

“…While our findings are consistent with some studies that show increases in GABAergic activity in response to pain (Gross et al, 2007;Kupers, Danielsen, Kehlet, Christensen, & Thomsen, 2009;Schulz et al, 2015), other studies have also reported reduced GABAergic activity in response to experimental pain (Cleve, Gussew, & Reichenbach, 2015;De Matos, Hock, Wyss, Ettlin, & Brügger, 2017). Differences between studies can be attributed to the duration of the noxious stimulus (tonic pain lasting several seconds/minutes vs. transient pain stimuli lasting <1second).…”

Improving magnetic resonance spectroscopy in the brainstem periaqueductal gray using spectral registration

“…Because these previous studies did not report spectral quality measures, a direct quality comparison is not possible. However, the spectral quality achieved here is comparable or even superior to studies, which examined other brainstem VOIs of larger size [44][45][46][47][48][49] and superior to one study with a brainstem VOI of similar size. 50 Spectral registration improving SNR and NAA linewidth by ∼5% and 23%, respectively, is relevant for several reasons.…”

Improving magnetic resonance spectroscopy in the brainstem periaqueductal grey using spectral registration

“…Because these previous studies did not report spectral quality measures, a direct quality comparison is not possible. However, the here achieved spectral quality is comparable or even superior to studies which examined other brainstem VOIs of larger size [44][45][46][47][48][49] and superior to one study with a brainstem VOI of similar size. 50 Regarding GABA, PRESS sequences have limitations because GABA's signal overlaps with resonances from other metabolites and is therefore difficult to detect.…”