Baseline vagal tone and pain reactivity: linking autonomic function to endogenous pain inhibition in women

Abstract – Introduction: – Conditioned pain modulation (CPM) is a laboratory test of the efficacy of endogenous pain inhibition. Although the vagus nerve is thought to contribute to analgesia via descending inhibitory pathways, its role in CPM remains unclear. In addition, as vagal tone fluctuates across the menstrual cycle due to hormonal changes, the menstrual cycle's influence on the vagal–CPM association warrants investigation.Methods: – Sixty-seven healthy females completed psychological questionnaires and underwent psychophysical assessments (1-minute tonic heat pain [THP] given alone and during CPM). An electrocardiogram was recorded at rest, and in 1-minute segments before, during, and after the THP alone, as well as during a conditioning stimulus (CPM paradigm). Heart rate variability was assessed using time- and frequency-domain indices. Menstrual phase was categorized as either follicular or luteal based on standard cycle-length division.Results: – The interaction between the resting root mean square of successive differences (RMSSD) and the menstrual cycle predicted better CPM efficiency. Post-hoc analysis revealed that the vagal–CPM association emerged solely in the follicular phase (β = −1.05, P = 0.010). Nevertheless, psychological factors did not influence the vagal–CPM association. The RMSSD broadly changed under pain with conditioning compared to baseline, with higher levels of RMSSD positively associated with CPM magnitude.Conclusions: – The findings suggest a tentative menstrual cycle–dependent association between baseline vagal tone and pain inhibition in healthy females. Further, greater vagal activity contributes to more efficient pain inhibition. Future studies should use within-subject designs to examine how interactions between vagal and sympathetic activity across the menstrual cycle influence pain modulation.