Sex differences in the reactivity of gastric myoelectrical activity and heart rate variability as putative psychophysiological markers in human pain research

Abstract

Background: This study explored the potential of electrogastrography (EGG) and heart rate variability (HRV) as psychophysiological markers in experimental pain research related to the gut-brain axis. We investigated responses to the experience of pain from the visceral (rectal distension) and somatic (cutaneous heat) pain modalities, with a focus on elucidating sex differences in EGG and HRV responses.

Methods: In a sample of healthy volunteers (29 males, 43 females), EGG and ECG data were collected during a baseline and a pain phase. Data were analyzed for changes in gastric myoelectrical activity and cardiac autonomic regulation, with special attention to sex-specific patterns and correlations with perceptual responses to visceral and somatic pain stimuli, assessed by visual analogue scale ratings.

Results: Acute pain induced significant instability in EGG slow-wave frequency and amplitude, increased tachygastria, and decreased normogastric spectral power, without evidence of sex differences. HRV analyses revealed increases in SDNN, RMSSD, and pNN50 during pain, indicating sympathovagal regulation changes. While there were no significant sex differences in EGG responses, only female participants exhibited significant correlations between visceral pain unpleasantness and EGG alterations. HRV measures, particularly time-domain parameters, showed sex differences, independent of pain-induced autonomic reactivity.

Conclusion: The experience of pain in the lower abdominal region may induce impaired gastric motility. EGG and HRV are sensitive to acute pain and offer insight into pain mechanisms along the gut-brain axis. While EGG responses were consistent across sexes, HRV revealed sex-specific differences, suggesting that autonomic regulation and gastric motility may be modulated differently by pain and psychosocial factors. Further research in patients with chronic visceral pain is warranted.

Keywords: autonomic nervous system; electrogastrography; gut-brain axis; heart rate variability; psychophysiology; sex differences; stress; visceral pain.

Figure 1

Illustration of EGG and ECG electrode positions. This figure was created using BioRender (www.biorender.com).

Figure 2

Relative Condition effects for the instability factor of the dominant frequency (IC_F, left panel) and amplitude (IC_A, right panel) of the EGG rhythm in the Pain vs. the NoPain conditions. The median relative Condition effect of the parameters (squares) and the 95% confidence intervals are presented with different colors for the whole sample of all subjects (green), females (black), and males (red). The plots were calculated by two nonparametric statistical models using the statistical toolbox nparLD (Noguchi et al., 2012) including (i) one group of all subjects and one repeated factor Condition and (ii) a Group factor (females and males), a factor Condition and Condition*Group interaction. Only Condition effects were statistically significant (for details, see text and Table 3).

Figure 3

Relative Condition effects for the normo-to-tachy ratio (NTT, left panel) and the power distributions of normal and tachygastric power distributions (Pow_n and Pow_t; middle and right panel respectively) in the Pain vs. the NoPain conditions. The median relative Condition effect of the parameters (squares) and the 95% confidence intervals are presented with different colors for the whole sample of all subjects (green), females (black), and males (red). The plots were calculated by two nonparametric statistical models using the statistical toolbox nparLD (Noguchi et al., 2012) including (i) one group of all subjects and a repeated factor Condition and (ii) a group factor (females and males), a factor Condition and Condition*Group interaction. Only Condition effects were statistically significant (for details, see text and Table 3).

Figure 4

Relative Condition effects for the time-domain HRV parameters standard deviation of the NN intervals (SDNN, left panel), root mean square of successive RR interval differences (RMSSD, middle panel), and percentage of adjacent NN intervals that differ from each other by more than 50 milliseconds (pNN50, right panel) between in the Pain vs. the NoPain conditions. The median relative Condition effect of the parameters (squares) and the 95% confidence intervals are presented with different colors for the whole sample of all subjects (green), females (black), and males (red). The plots were calculated by two nonparametric statistical models using the statistical toolbox nparLD (Noguchi et al., 2012) including (i) one group of all subjects and one repeated factor Condition and (ii) a Group factor (females and males), a factor Condition and Condition*Group interaction. Condition effects were statistically significant for all parameters; Group effects were significant for RMSSD and pNN50 (for details, see text and Table 4).

Figure 5

Correlations between perceived visceral pain intensity and unpleasantness, assessed with VAS, and the EGG parameters instability factor of frequency (A,B) and the normo-to-tachy ratio (C,D). Groups are presented with different colors for females (black) and for males (red). The non-parametric estimation of Kendall’s Tau correlation coefficients was significant only in the female group (for details, see Supplementary Table S1).