Background & Aims
Conditioned pain modulation (CPM) (i.e., diffuse noxious inhibitory controls) is the psychophysical test of the ‘pain inhibits pain’ phenomenon. CPM responses vary between individuals, with some showing inefficient CPM [1,2]. CPM magnitude predicts post-operative pain [3] and response to pharmacological treatments [4], suggesting it might have a clinical use. CPM quantifies the functioning of the descending inhibitory pathways that are under top-down modulation of subcortical and cortical brain areas [5]. Recent studies highlight the role of vagal activity in pain modulation [6,7]. Yet, its direct involvement in CPM and CPM efficacy was not examined. Thus, this study aimed to examine the role of the vagus in CPM response and efficiency in healthy women as part of a large study that focused on the female population. Further, as the vagal activity and reactivity are moderated by weight, psychological traits, and emotional state, these factors were also included in the analyses.
Methods
Eighty-six healthy females completed questionnaires measuring anxiety, mood, emotion regulation, fear of pain, and pain catastrophizing. Afterward, 5 minutes of electrocardiogram (ECG) recording at rest was measured. Then, the temperature of heat pain-60 (60 on 0-100 numerical pain scale; NPS) was determined and used for 60-second tonic heat pain applied to the forearm (i.e. test-stimulus), alone and during conditioning stimulus (contralateral hand immersion in a hot water bath). Pain ratings were provided every 10 seconds using the NPS. ECG was recorded 60 seconds before (baseline), during (reactivity), and after (recovery) the test stimulus, alone and during conditioning stimulus. ECG at rest, baseline, reactivity, and recovery were analyzed at time-domain of heart rate variability (HRV). Statistical analyses included correlations between baseline measures and CPM efficacy, logistic regression to predict CPM responsiveness, and mixed model ANOVA to examine vagal pain reactivity.
Results
Forty-seven participants (54.6%) showed a CPM effect (i.e. CPM responders). CPM magnitude did not correlate with pain-60 temperature, demographic, or psychological factors. Comparisons between responders and non-responders revealed between-groups differences only in HRV measure of root mean square of successive differences (log rMSSD) at rest [responders:1.549 (0.25), non-responders:1.43 (0.24); t(82)=2.044, p=.044]. Logistic regression showed that among all collected baseline variables, log rMSSD at rest and body mass index (BMI) significantly predicted CPM response (?2(2)=8.23, p=.016), explained 13.6% of the variance and correctly predicted 63.6% of cases.
During both tonic heat pain and CPM, rMSSD decreased compared to baseline [log rMSSD change .49 (95% CI, .02 to .078), p<.001; log rMSSD change .097 (95% CI, .048 to 0.147), p<.001; respectively], similarly in responders and non-responders. Lastly, higher rMSSD values during CPM correlated with the CPM magnitude (r=-.355 p<.001)
Conclusions
Our findings underscore the significant influence of vagal activity on CPM efficiency. Specifically, the individual basic vagal tone in females predicts CPM efficiency; a higher vagal tone is associated with greater CPM efficiency. Moreover, vagal reactivity during CPM is related to the efficiency of pain inhibition. Hence, our comprehensive approach, integrating psychological and physiological measures, yields direct evidence into the regulatory role of the vagus during pain inhibition. These findings have implications for the development of mechanism-based treatments for chronic pain conditions characterized by impaired CPM. Future intervention studies should explore whether interventions aimed at enhancing vagal tone can improve CPM efficacy, and accordingly, incorporate them as part of a pain management strategy.
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