Specificity of hemodynamic brain responses to painful stimuli: a functional near-infrared spectroscopy study

Meryem A Yücel, Christopher M Aasted, Mihayl P Petkov, David Borsook, David A Boas, Lino Becerra, Meryem A Yücel, Christopher M Aasted, Mihayl P Petkov, David Borsook, David A Boas, Lino Becerra

Abstract

Assessing pain in individuals not able to communicate (e.g. infants, under surgery, or following stroke) is difficult due to the lack of non-verbal objective measures of pain. Near-infrared spectroscopy (NIRS) being a portable, non-invasive and inexpensive method of monitoring cerebral hemodynamic activity has the potential to provide such a measure. Here we used functional NIRS to evaluate brain activation to an innocuous and a noxious electrical stimulus on healthy human subjects (n = 11). For both innocuous and noxious stimuli, we observed a signal change in the primary somatosensory cortex contralateral to the stimulus. The painful and non-painful stimuli can be differentiated based on their signal size and profile. We also observed that repetitive noxious stimuli resulted in adaptation of the signal. Furthermore, the signal was distinguishable from a skin sympathetic response to pain that tended to mask it. Our results support the notion that functional NIRS has a potential utility as an objective measure of pain.

Conflict of interest statement

D.A.B. is an inventor on a technology licensed to TechEn, a company whose medical pursuits focus on noninvasive optical brain monitoring. D.A.B.'s interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies.

Figures

Figure 1. Localized hemodynamic response to left…
Figure 1. Localized hemodynamic response to left thumb innocuous and noxious electrical stimuli.
Ipsilateral (left hemisphere) and contralateral (right hemisphere) hemodynamic response to left thumb innocuous (top panels) and noxious electrical stimuli (bottom panels). Group average results (n = 11) for the changes in HbO (red), HbR (blue), HbT (green). The letters a, b and c on the top right panel correspond to the same letters on Figure 7, panel B and Table 1.
Figure 2. Comparison of the hemodynamic response…
Figure 2. Comparison of the hemodynamic response to innocuous and noxious stimuli in the first three minutes on the motor-sensory region.
Changes in HbO (top, left) and HbR (bottom, left) as a response to innocuous stimuli (blue) and noxious stimuli (red). Yellow bars show the interval chosen to obtain the mean responses depicted in the scatter plots and stars indicate a statistically significant difference. The right panels show a scatter plot comparing the hemodynamic response for each subject averaged over the yellow bar during the first three minutes for HbO (top) and HbR (bottom). The horizontal green bar shows the stimulus duration.
Figure 3. Comparison of the hemodynamic response…
Figure 3. Comparison of the hemodynamic response to innocuous and noxious stimuli in the first three minutes on the frontal region.
Changes in HbO (top, left) and HbR (bottom, left) as a response to innocuous stimuli (blue) and noxious stimuli (red). Yellow bars show the interval chosen to obtain the mean responses depicted in the scatter plots. The right panels show a scatter plot comparing the hemodynamic response for each subject averaged over the yellow bar during the first three minutes for HbO (top) and HbR (bottom). The horizontal green bar shows the stimulus duration.
Figure 4. Habituation in the hemodynamic response…
Figure 4. Habituation in the hemodynamic response to noxious stimuli on the motor-sensory region.
Comparison of HbO (top, left panels) and HbR changes (bottom, left panels) in response to innocuous and noxious electrical stimuli in the first three minutes (blue) with the HbO and HbR changes in the second three minutes (red). Error bars represent the standard error across subjects (n = 11). Yellow bars show the interval chosen to obtain the mean response depicted for each subject in the scatter plots and stars indicate a statistically significant difference. The right panels show scatter plots comparing the hemodynamic response averaged over the yellow bar during the first and second three minutes for HbO (top) and HbR (bottom). The horizontal green bar shows the stimulus duration.
Figure 5. Habituation in the hemodynamic response…
Figure 5. Habituation in the hemodynamic response to noxious stimuli on the frontal region.
Comparison of HbO (top, left panels) and HbR changes (bottom, left panels) in response to innocuous and noxious electrical stimuli in the first three minutes (blue) with the HbO and HbR changes in the second three minutes (red). Error bars represent the standard error across subjects (n = 11). Yellow bars show the interval chosen to obtain the mean response depicted for each subject in the scatter plots and stars indicate a statistically significant difference. The right panels show scatter plots comparing the hemodynamic response averaged over the yellow bar during the first and second three minutes for HbO (top) and HbR (bottom). The horizontal green bar shows the stimulus duration.
Figure 6. Hemodynamic response to left thumb…
Figure 6. Hemodynamic response to left thumb noxious electrical stimuli at long separation channels (panels A and B) and short separation channels (panels C and D) without short separation regression.
Group average results (n = 11) for the changes in HbO (red), HbR (blue), HbT (green). The letter-number combinations on panel D (from s1 to s6) correspond to the same letter-number combinations on Figure 7, panel B.
Figure 7. Probe placement and stimulus paradigm.
Figure 7. Probe placement and stimulus paradigm.
The locations of the detectors (blue dots), the sources (red dots), the channels (green lines) and the sensitivity profile are shown for one subject (panel A). The optodes and the channels are displayed on the scalp and the sensitivity profile is displayed on the cortex. The sensitivity profile is displayed on a logarithmic scale and spans two orders of magnitude (arbitrary units). The channels used for frontal (purple) and motor-sensory (pink) regions are labelled with stars. The letter-number combinations on panel B (long separation channels: a, b, c and short separation channels: s1 to s6) correspond to the same letter-number combinations on Figure 1, Figure 6 and Table 1. Panel C: Stimulus paradigm: innocuous stimuli (blue lines), noxious stimuli (green lines).

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