To understand neurochemical brain responses to pain, proton magnetic resonance spectroscopy (1H-MRS) is used in humans in vivo to examine various metabolites. Recent MRS investigations have adopted a functional approach, where acquisitions of MRS are performed over time to track task-related changes. Previous studies suggest glutamate is of primary interest, as it may play a role during cortical processing of noxious stimuli. The objective of this study was to examine the metabolic effect (i.e., glutamate) in the anterior cingulate cortex during noxious stimulation using fMRS. The analysis addressed changes in glutamate and glutamate + glutamine (Glx) associated with the onset of pain, and the degree by which fluctuations in metabolites corresponded with continuous pain outcomes. Results suggest healthy participants undergoing tonic noxious stimulation demonstrated increased concentrations of glutamate and Glx at the onset of pain. Subsequent reports of pain were not accompanied by corresponding changes in glutamate of Glx concentrations. An exploratory analysis on sex revealed large effect size changes in glutamate at pain onset in female participants, compared with medium-sized effects in male participants. We propose a role for glutamate in the ACC related to the detection of a noxious stimulus.
Contact heat evoked potentials (CHEPs) represent an objective and non-invasive measure to investigate the integrity of the nociceptive neuraxis. The clinical value of CHEPs is mostly reflected in improved diagnosis of peripheral neuropathies and spinal lesions. One of the limitations of conventional contact heat stimulation is the relatively slow heating ramp (70 °C/s). This is thought to create a problem of desynchronized evoked responses in the brain, particularly after stimulation in the feet. Recent technological advancements allow for an increased heating ramp of contact heat stimulation, however, to what extent these improve the acquisition of evoked potentials is still unknown. In the current study, 30 healthy subjects were stimulated with contact heat at the hand and foot with four different heating ramps (i.e., 150 °C/s, 200 °C/s, 250 °C/s, and 300 °C/s) to a peak temperature of 60 °C. We examined changes in amplitude, latency, and signal-to-noise ratio (SNR) of the vertex (N2-P2) waveforms. Faster heating ramps decreased CHEP latency for hand and foot stimulation (hand: F = 18.41, p < 0.001; foot: F = 4.19, p = 0.009). Following stimulation of the foot only, faster heating ramps increased SNR (F = 3.32, p = 0.024) and N2 amplitude (F = 4.38, p = 0.007). Our findings suggest that clinical applications of CHEPs should consider adopting faster heating ramps up to 250 °C/s. The improved acquisition of CHEPs might consequently reduce false negative results in clinical cohorts. From a physiological perspective, our results demonstrate the importance of peripherally synchronizing afferents recruitment to satisfactorily acquire CHEPs.
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