Investigating the effects of artificial baroreflex stimulation on pain perception: A comparative study in no-pain and chronic low back pain individuals

The autonomic nervous system (ANS) and pain exhibit a reciprocal relationship, where acute pain triggers ANS responses, whereas resting ANS activity can influence pain perception. Nociceptive signalling can also be altered by 'top-down' processes occurring in the brain, brainstem and spinal cord, known as 'descending modulation'. By employing the conditioned pain modulation (CPM) paradigm, we previously revealed a connection between reduced low-frequency heart rate variability and CPM. Individuals with chronic pain often experience both ANS dysregulation and impaired CPM. Baroreceptors, which contribute to blood pressure and heart rate variability regulation, may play a significant role in this relationship, although their involvement in pain perception and their functioning in chronic pain have not been sufficiently explored. In the present study, we combined artificial 'baroreceptor stimulation' in both pressure pain and CPM paradigms, seeking to explore the role of baroreceptors in pain perception and descending modulation. In total, 22 individuals with chronic low back pain (CLBP) and 29 individuals with no-pain (NP) took part in the present study. We identified a differential modulation of baroreceptor stimulation on pressure pain between the groups of NP and CLBP participants. Specifically, NP participants perceived less pain in response to baroreflex activation, whereas CLBP participants exhibited increased pain sensitivity. CPM scores were associated with baseline measures of baroreflex sensitivity in both CLBP and NP participants. Our data support the importance of the baroreflex in chronic pain and a possible mechanism of dysregulation involving the interaction between the ANS and descending pain modulation. imageKey points Baroreflex stimulation has different effects on pressure pain in participants with chronic pain compared to matched individuals with no-pain. Baroreceptor activation decreases pain in participants with no-pain but increases pain perception in participants with chronic pain. Baroreflex sensitivity is associated with conditioned pain modulation in both groups of chronic pain and no-pain participants. The reactivity of the baroreflex during autonomic stress demonstrated a positive correlation with Pain Trait scores in participants with chronic back pain. figure legend There is a strict interaction between the autonomic nervous system (ANS), as expression of the cardiovascular state of the body, and pain. Nociception is modulated by 'top-down' descending pain control systems from the brain to the brainstem and spinal cord. Here, we perturbed the ANS by applying a non-painful negative pressure at the level of the carotid bifurcation to stimulate baroreceptors and we evaluated the integrity of a pain modulation mechanism by a conditioned pain modulation (CPM) assessment, in which participants received noxious pressure (used as test stimulus) delivered simultaneously with a continuous pressure stimulation (used as conditioning stimulus) on the thumbnails. We aimed to examine the relationship between ANS reactivity and CPM efficiency in two groups of 'no-pain' and 'chronic low back pain' participants, with a focus on the specific involvement of baroreceptors in this interaction. In our sample, baroreflex activation decreased pain in pain-free participants but increased pain perception in those with chronic pain, indicating that this activation may play a role in the ANS-pain interaction and that is disrupted in chronic pain states. We suggest the potential importance of the baroreflex in pain perception and indicate potential avenues of exploiting these mechanisms to improve treatment of individuals with chronic pain. image