There are bi-directional interactions between the autonomic nervous system (ANS) and pain. This is likely underpinned by a substantial overlap between brain areas of the central autonomic network and areas involved in pain processing and modulation. To date, however, relatively little is known about the neuronal substrates of the ANS-pain association. Here, we acquired resting state fMRI scans in 21 healthy subjects at rest and during tonic noxious cold stimulation. As indicators of autonomic function, we examined how heart rate variability (HRV) frequency measures were influenced by tonic noxious stimulation and how these variables related to participants’ pain perception and to brain functional connectivity in regions known to play a role in both ANS regulation and pain perception, namely the right dorsal anterior cingulate cortex (dACC) and periaqueductal gray (PAG). Our findings support a role of the cardiac ANS in brain connectivity during pain, linking functional connections of the dACC and PAG with measurements of low frequency (LF)-HRV. In particular, we identified a three-way relationship between the ANS, cortical brain networks known to underpin pain processing, and participants’ subjectively reported pain experiences. LF-HRV both at rest and during pain correlated with functional connectivity between the seed regions and other cortical areas including the right dorsolateral prefrontal cortex (dlPFC), left anterior insula (AI), and the precuneus. Our findings link cardiovascular autonomic parameters to brain activity changes involved in the elaboration of nociceptive information, thus beginning to elucidate underlying brain mechanisms associated with the reciprocal relationship between autonomic and pain-related systems.

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA‐Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega‐analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between‐country transfer of subject‐level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega‐analyses.

There is a strict interaction between the autonomic nervous system (ANS) and pain, which might involve descending pain modulatory mechanisms. The periaqueductal grey (PAG) is involved both in descending pain modulation and ANS, but its role in mediating this relationship has not yet been explored. Here, we sought to determine brain regions mediating ANS and descending pain control associations. Thirty participants underwent conditioned pain modulation (CPM) assessments, in which they rated painful pressure stimuli applied to their thumbnail, either alone or with a painful cold contralateral stimulation. Differences in pain ratings between ‘pressure‐only’ and ‘pressure + cold’ stimuli provided a measure of descending pain control. In 18 of the 30 participants, structural scans and two functional MRI assessments, one pain‐free and one during cold‐pain were acquired. Heart rate variability (HRV) was simultaneously recorded. Normalised low‐frequency HRV (LF‐HRVnu) and the CPM score were negatively correlated; individuals with higher LF‐HRVnu during pain reported reductions in pain during CPM. PAG‐ventro‐medial prefrontal cortex (vmPFC) and PAG‐rostral ventromedial medulla (RVM) functional connectivity correlated negatively with the CPM. Importantly, PAG‐vmPFC functional connectivity mediated the strength of the LF‐HRVnu‐CPM association. CPM response magnitude was also negatively correlated with vmPFC GM volume. Our multi‐modal approach, using behavioural, physiological and MRI measures, provides important new evidence of interactions between ANS and descending pain mechanisms. ANS dysregulation and dysfunctional descending pain modulation are characteristics of chronic pain. We suggest that further investigation of body‐brain interactions in chronic pain patients may catalyse the development of new treatments. image Key points: Heart rate variability (HRV) is associated with descending pain modulation as measured by the conditioned pain modulation protocol (CPM). There is an association between CPM scores and the functional connectivity between the periaqueductal grey (PAG) and ventro‐medial prefrontal cortex (vmPFC). CPM scores are also associated with vmPFC grey matter volume. The strength of functional connectivity between the PAG and vmPFC mediates the association between HRV and CPM. Our data provide new evidence of interactions between the autonomic nervous system and descending pain mechanisms.

Objective: Spontaneous or experimentally induced high blood pressure (BP) is associated with reduced pain perception, known as BP-related hypoalgesia. Despite its clinical implications, such as the interference with early detection of myocardial infarction in ‘at risk’ groups, the size of the association between high BP and pain has not yet been quantified. Moreover, the distinct association between high BP and physiological or psychological components of pain has not yet been considered so far. The aim of this study was to overcome this gap by performing separate meta-analyses on nociceptive response versus quantifiable perceptual measures of pain in relation to high BP. Methods: PubMed and Web of Knowledge databases were searched for English language studies conducted in humans. Fifty-nine studies were eligible for the analyses. Pooled effect sizes (Hedges’ g) were compared. Random effect models were used. Results show that higher BP is significantly associated with lower nociceptive response (g = 0.38; k = 6) and reduced pain perception, assessed by quantifiable measures (g = 0.48; k = 59). Results: The association between BP and pain perception, derived from highly heterogeneous studies, was characterized by significant publication bias. BP assessment, pain assessment, site of pain stimulation, percentage of female participants in the sample, and control for potential confounders were significant moderators. Conclusion: Current meta-analytic results confirm the presence of BP-related hypoalgesia and point towards the need for a better understanding of its underlying mechanisms.