Functional Neuroimaging of Nociceptive and Pain‐Related Activity in the Spinal Cord and Brain: Insights From Neurovascular Coupling Studies

Abstract

Spinal cord and brain processes underlie pain perception, which produces systemic cardiovascular changes. In turn, the autonomic nervous system regulates vascular function in the spinal cord and brain in order to adapt to these systemic changes, while neuronal activity induces local vascular changes. Thus, autonomic regulation and pain processes in the brain and spinal cord are tightly linked and interrelated. The objective of this topical review is to discuss work on neurovascular coupling during nociceptive processing in order to highlight supporting evidence and limitations for the use of cerebral and spinal fMRI to investigate pain mechanisms and spinal nociceptive processes. Work on functional neuroimaging of pain is presented and discussed in relation to available neurovascular coupling studies and related issues. Perspectives on future work are also discussed with an emphasis on differences between the brain and the spinal cord and on different approaches that may be useful to improve current methods, data analyses and interpretation. In summary, this review highlights the lack of data on neurovascular coupling during nociceptive stimulation and indicates that hemodynamic and BOLD responses measured with fMRI may be biased by nonspecific vascular changes. Future neuroimaging studies on nociceptive and pain-related processes would gain further understanding of neurovascular coupling in the brain and spinal cord and should take into account the effects of systemic vascular changes that may affect hemodynamic responses. Anat Rec, 301:1585-1595, 2018. © 2018 Wiley Periodicals, Inc.

fMRI indicates cortical activation through TRPV1 modulation during acute gouty attacks

“…Indeed, elevated MABP has been considered a confounding variable of fMRI hemodynamic responses 28,29 . This is an issue in nociceptive fMRI: noxious stimuli not only elicit neural activity that cause hemodynamic changes, but also abrupt changes in MABP that can lead to a stimulus-correlated increase in the influx of oxygenated blood from the periphery into the brain vasculature and thus to an increase in cerebral blood flow (CBF) 30 . The BOLD effects of large veins are prone to reflect abrupt elevations in MABP in response to the stimulus.…”

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“…Both abrupt elevations in MABP and remote vasodilatory projections of arousal nuclei can produce hemodynamic readouts that are indistinguishable from neurovascular coupling. This problem has hardly been explored and is currently considered a major hurdle for interpreting experimental data related to nociceptive fMRI in (ventilated) rodents (Paquette et al, 2018).…”

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“…Functional magnetic resonance imaging (fMRI) allows the investigation of a wide variety of brain functions in human and animal models, including pain mechanisms (Apkarian et al, 2011;Da Silva & Seminowicz, 2019;Duerden & Albanese, 2013;Lowe et al, 2007;Paquette et al, 2018;van der Miesen et al, 2019;Wager et al, 2013). The most common fMRI methods rely on the blood oxygen level-dependent (BOLD) signal (Ogawa et al, 1990).…”

“…Therefore, isoflurane and medetomidine may affect vascular functions and NVC differently and may produce differences in stimulus‐related BOLD signal changes, leading to different conclusions on brain activity (Nasrallah et al, 2014). In addition, noxious stimulation evokes increases in mean arterial pressure (MAP), which may not be compensated by autoregulation (Jeffrey‐Gauthier et al, 2013; Uchida et al, 2017; Paquette et al, 2018, Paquette, Tokunaga, et al, 2019b). This may affect NVC differently under medetomidine and isoflurane anaesthesia, considering their different effects on vascular functions.…”