Muscle sympathetic nerve activity‐coupled changes in brain activity during sustained muscle pain

Abstract

IntroductionLong‐lasting experimental muscle pain elicits divergent muscle sympathetic responses, with some individuals exhibiting a persistent increase in muscle sympathetic nerve activity (MSNA), and others a decrease. These divergent responses are thought to result from sustained functional changes in specific brain regions that modulate the cardiovascular responses to pain.AimThe aim of this study was to investigate brain regions that are functionally coupled to the generation of an MSNA burst at rest and to determine their behavior during tonic muscle pain.MethodsFunctional magnetic resonance imaging of the brain was performed concurrently with microelectrode recording of MSNA from the common peroneal nerve during a 40 min infusion of hypertonic saline into the ipsilateral tibialis anterior muscle of 37 healthy human subjects.ResultsAt rest, blood oxygen level‐dependent signal intensity coupled to bursts of MSNA increased in the rostral ventrolateral medulla, insula, dorsolateral prefrontal cortex, posterior cingulate cortex, and precuneus and decreased in the region of the midbrain periaqueductal gray. During pain, MSNA‐coupled signal intensity was greater in the region of the nucleus tractus solitarius, midbrain periaqueductal gray, dorsolateral prefrontal, medial prefrontal, and anterior cingulate cortices, than at rest. Conversely, MSNA‐coupled signal intensity decreased during pain in parts of the prefrontal cortex.ConclusionsThese results suggest that multiple brain regions are recruited in a burst‐to‐burst manner, and the magnitude of these signal changes is correlated to the overall change in MSNA amplitude during tonic muscle pain.

The role of the paravertebral ganglia in human sympathetic neural discharge patterns

“…; Kobuch et al . ). In this conjecture, the strength of preganglionic inputs to postganglionic neurons possessing larger diameter axons would reflect a subpopulation of descending neural signals from higher cortical sites that are not under direct baroreflex regulation.…”

Identifying Increases in Activity of the Human RVLM Through MSNA-Coupled fMRI

“…Mean data, showing the correlations between the change in BOLD signal intensity and change in MSNA burst amplitude, from 37 participants are illustrated in Figure 7. These results indicate that several areas of the brain are engaged in a burst-to-burst manner, with the magnitudes of these changes in signal intensity being correlated to the overall change in MSNA amplitude during tonic muscle pain (Kobuch et al, 2018). Interestingly, some important brain regions did not display pain-related changes.…”

“…At rest, BOLD signal intensity was strongly coupled to bursts of MSNA in the RVLM, insula, dlPFC, PCC, and precuneus, and decreased in the region of the midbrain PAG. During pain, MSNA-coupled BOLD signal intensity was significantly higher in the region of the NTS and ventrolateral PAG on the right, dlPFC and ACC on the right, and insula and mPFC on the left; conversely, MSNA-coupled signal intensity decreased during pain in parts of the left dlPFC and mPFC (Kobuch et al, 2018). Mean data, showing the correlations between the change in BOLD signal intensity and change in MSNA burst amplitude, from 37 participants are illustrated in Figure 7.…”

“…We recently examined functional changes in the brain during experimental muscle pain, induced by a 40-min infusion of hypertonic saline into a leg muscle, which causes a sustained increase in MSNA in some participants but a sustained decrease in others; the pattern is reproducible in a given individual and we recently showed that those in whom MSNA increased during tonic muscle pain exhibited increases in BOLD signal intensity in several areas (Kobuch et al, 2017(Kobuch et al, , 2018, including the anterior insula and anterior medial prefrontal cortex (mPFC) on the left, and dlPFC and anterior cingulate cortex (ACC) on the right, while signal intensity decreased in the mPFC and dlPFC on the left (Figure 5). We also saw an increase in signal intensity in the left DMH, which fits with the role of this nucleus in the generation of autonomic responses to stress (DiMicco et al, 2002;Fontes et al, 2017).…”

“…In all regions there is a significant linear relationship between the change in BOLD signal intensity and the change in burst amplitude of MSNA. Reproduced, with permission, from Kobuch et al (2018).…”