Inter-Individual Responses to Experimental Muscle Pain: Baseline Physiological Parameters Do Not Determine Whether Muscle Sympathetic Nerve Activity Increases or Decreases During Pain

Abstract

We have previously reported that there are inter-individual differences in the cardiovascular responses to experimental muscle pain, which are consistent over time: intramuscular infusion of hypertonic saline, causing pain lasting ~60 min, increases muscle sympathetic nerve activity (MSNA)—as well as blood pressure and heart rate—in certain subjects, but decrease it in others. Here, we tested the hypothesis that baseline physiological parameters (resting MSNA, heart rate, blood pressure, heart rate variability) determine the cardiovascular responses to long-lasting muscle pain. MSNA was recorded from the common peroneal nerve, together with heart rate and blood pressure, during a 45-min intramuscular infusion of hypertonic saline solution into the tibialis anterior of 50 awake human subjects (25 females and 25 males). Twenty-four subjects showed a sustained increase in mean amplitude of MSNA (160.9 ± 7.3%), while 26 showed a sustained decrease (55.1 ± 3.5%). Between the increasing and decreasing groups there were no differences in baseline MSNA (19.0 ± 1.5 vs. 18.9 ± 1.2 bursts/min), mean BP (88.1 ± 5.2 vs. 88.0 ± 3.8 mmHg), HR (74.7 ± 2.0 vs. 72.8 ± 1.8 beats/min) or heart rate variability (LF/HF 1.8 ± 0.2 vs. 2.2 ± 0.3). Furthermore, neither sex nor body mass index had any effect on whether MSNA increased or decreased during tonic muscle pain. We conclude that the measured baseline physiological parameters cannot account for the divergent sympathetic responses during tonic muscle pain.

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

“…Consistent with our previous investigations, we found that tonic muscle pain resulted in divergent muscle sympathetic responses [Fazalbhoy et al, ; Kobuch et al, ]. Since these opposite MSNA responses were associated with different signal intensity changes in cortical regions involved in higher‐order emotional and cognitive function, such as the prefrontal and cingulate cortices, one might expect that psychological differences underlie the different MSNA responses.…”

“…We recently found that prolonged muscle pain, induced by intramuscular infusion of hypertonic saline, is accompanied by two patterns of change in MSNA, with subjects showing either a sustained increase or a sustained decrease in MSNA [Fazalbhoy et al, , 2014Kobuch et al, 2015Kobuch et al, , 2016 for review see Burton et al, 2016]. These divergent patterns of MSNA are reproducible over time [Fazalbhoy et al, 2014], and not based on sex, or differences in resting MSNA, blood pressure, or heart rate [Kobuch et al, 2015]. Moreover, anxiety and attitudes to pain do not account for these divergent sympathetic responses to muscle pain [Kobuch et al, 2016].…”

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.…”

“…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, 2012Kobuch, Fazalbhoy, Brown, Henderson, & Macefield, 2017;Kobuch, Fazalbhoy, Brown, & Macefield, 2015. These individual differences are reliable across multiple experimental sessions in individuals (Fazalbhoy et al, 2014) and are not influenced by sex, age, anxiety levels, attitudes to pain, or resting MSNA, BP, or HR levels (Kobuch et al, 2015(Kobuch et al, , 2016.…”

“…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., , ). 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., ).…”