Central circuitry responsible for the divergent sympathetic responses to tonic muscle pain in humans

Abstract

Experimentally induced tonic muscle pain evokes divergent muscle vasoconstrictor responses, with some individuals exhibiting a sustained increase in muscle sympathetic nerve activity (MSNA), and others a sustained decrease. These patterns cannot be predicted from an individual's baseline physiological or psychological measures. The aim of this study was to investigate whether the different muscle sympathetic responses to tonic muscle pain were associated with differential changes in regional brain activity. Functional magnetic resonance imaging (fMRI) of the brain was performed concurrently with microelectrode recording of MSNA from the peroneal nerve during a 40-min infusion of hypertonic saline into the ipsilateral tibialis anterior muscle. MSNA increased in 26 and decreased in 11 of 37 subjects during tonic muscle pain. Within the prefrontal and cingulate cortices, precuneus, nucleus accumbens, caudate nucleus, and dorsomedial hypothalamus, blood oxygen level dependent (BOLD) signal intensity increased in the increasing-MSNA group and remained at baseline or decreased in the decreasing-MSNA group. Similar responses occurred in the dorsolateral pons and in the region of the rostral ventrolateral medulla. By contrast, within the region of the dorsolateral periaqueductal gray (dlPAG) signal intensity initially increased in both groups but returned to baseline levels only in the increasing-MSNA group. These results suggest that the divergent sympathetic responses to muscle pain result from activation of a neural pathway that includes the dlPAG, an area thought to be responsible for the behavioral and cardiovascular responses to psychological rather than physical stressors. Hum Brain Mapp 38:869-881, 2017. © 2016 Wiley Periodicals, Inc.

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

“…Hypertonic saline infusion into the tibialis anterior muscle induced pain that was described as dull, aching, and throbbing. Consistent with our previous investigations, we found that tonic muscle pain evoked increases in MSNA amplitude in some individuals and decreases in others (Fazalbhoy et al., , ; Kobuch et al., , , ). These changes began approximately 20 volumes (160 s) after the start of the hypertonic infusion, at approximately the same time as subjects began to perceive pain, and remained fairly stable for the duration of the pain period.…”

“…In our previous study, we found that the insular cortex did not display sustained signal intensity changes coupled to sustained changes in MSNA during tonic muscle pain (Kobuch et al., ). This is surprising given the growing body of the literature describing insular cortex changes during various cardiovascular challenges (Beissner et al., ; Butcher & Cechetto, ; Harper et al., ; Henderson et al., ; Macefield et al., ; Macey et al., ).…”

“…We have since shown that prolonged (~45 min) muscle pain in humans evokes a mixed cardiovascular response, with some individuals showing a sustained MSNA increase, and others a sustained decrease (Fazalbhoy, Birznieks, & Macefield, , ; Kobuch, Fazalbhoy, Brown, Henderson, & Macefield, ; Kobuch, Fazalbhoy, Brown, & Macefield, , ). These individual differences are reliable across multiple experimental sessions in individuals (Fazalbhoy et al., ) and are not influenced by sex, age, anxiety levels, attitudes to pain, or resting MSNA, BP, or HR levels (Kobuch et al., , ).…”

“…These individual differences are reliable across multiple experimental sessions in individuals (Fazalbhoy et al., ) and are not influenced by sex, age, anxiety levels, attitudes to pain, or resting MSNA, BP, or HR levels (Kobuch et al., , ). Using concurrent functional magnetic resonance imaging (fMRI) and microneurography, we recently found that areas of the prefrontal, cingulate and precuneus cortices, hypothalamus, midbrain, and medulla displayed sustained increases in BOLD (blood oxygen level dependent) signal intensity in those individuals who displayed sustained increases in MSNA compared with those who displayed sustained decreases (Kobuch et al., ). That study explored continuous signal intensity changes throughout the whole scanning period, with subjects separated into two groups according to whether they exhibited an increase or a decrease in MSNA during pain (Kobuch et al., ).…”

“…Using concurrent functional magnetic resonance imaging (fMRI) and microneurography, we recently found that areas of the prefrontal, cingulate and precuneus cortices, hypothalamus, midbrain, and medulla displayed sustained increases in BOLD (blood oxygen level dependent) signal intensity in those individuals who displayed sustained increases in MSNA compared with those who displayed sustained decreases (Kobuch et al., ). That study explored continuous signal intensity changes throughout the whole scanning period, with subjects separated into two groups according to whether they exhibited an increase or a decrease in MSNA during pain (Kobuch et al., ). However, while investigating overall signal intensity changes associated with sustained increases or decreases in MSNA responses during tonic muscle pain, it did not explore MSNA‐coupled changes in BOLD signal intensity, that is, regions in which signal intensity increased or decreased during each MSNA burst.…”