Linking Pain Sensation to the Autonomic Nervous System: The Role of the Anterior Cingulate and Periaqueductal Gray Resting-State Networks

Abstract

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.

Approach-Avoidance Decisions Under Threat: The Role of Autonomic Psychophysiological States

“…A region that may play a critical role in integrating value across modalities is the anterior cingulate cortex (ACC; Botvinick et al, 2004 ; Aupperle et al, 2015 ; Schlund et al, 2016 ). Importantly, the dorsal ACC (dACC) shows specific modulation of connectivity with the amygdala by exposure to threat ( Carlson et al, 2013 ) and with the PAG by nociceptive stimuli ( Hohenschurz-Schmidt et al, 2020 ). Although much literature localizes value integration in the dACC, some research also points to the neighboring subgenual area ( Talmi et al, 2009 ; Park et al, 2011 ) and broader regions of the cingulate cortex ( Roy et al, 2014 ; Gold et al, 2015 ).…”

Increased sympathetic and haemodynamic responses to exercise and muscle metaboreflex activation in post‐menopausal women with rheumatoid arthritis

“…inflammatory reflex; Tracey, 2002), as well as between autonomic dysfunction and pain (Hohenschurz‐Schmidt et al . 2020). This is the first study to show that the haemodynamic responses to exercise and muscle metaboreflex activation are associated with inflammation and pain in a chronic inflammatory and painful disease.…”

Safe in my heart: resting heart rate variability longitudinally predicts emotion regulation, worry and sense of safeness during COVID-19 lockdown

“…One-hundred and seventy-two healthy individuals, whose resting vmHRV was assessed between May 2018 and October 2019 (Time 0; T0) during participation in previous studies (16)(17)(18)(19), were recruited. Specific information about vmHRV assessment can be found in the original studies (16)(17)(18)(19).…”