Investigating the Effects of Artificial Baroreflex Stimulation on Pain Perception: A Comparative Study in Healthy Participants and Individuals with Chronic Low Back Pain

The autonomic nervous system (ANS) and pain exhibit a reciprocal relationship, whereupon acute pain triggers ANS responses, while 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, our previous study revealed a connection between reduced low-frequency heart rate variability (HRV) and CPM. Chronic pain patients often experience both ANS dysregulation and impaired CPM. Baroreceptors, which contribute to blood pressure and HRV regulation, may play a significant role in this relationship, but their involvement in pain perception and their functioning in chronic pain have not been sufficiently explored. In this 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. 22 patients with chronic low back pain (CLBP) and 29 healthy controls (HC) took part in this study. We identified a relationship between baroreflex functioning and perception of pressure pain, finding differential modulation of pressure pain between diagnostic groups. Specifically, HC participants perceived less pain in response to baroreflex activation, whereas CLBP patients exhibited increased pain sensitivity. CPM scores were associated with baseline measures of baroreflex efficiency in both patients and controls. Our data support the importance of the baroreflex in chronic pain and a possible mechanism of dysregulation involving the interaction between the autonomic nervous system and descending pain modulation. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Effic-Grunenthal Award 2019 and the Medical Research Council. Dr Matthew Howard is supported by the NIHR Biomedical Research Centre and Clinical Research Facility at South London and Maudsley NHS Foundation Trust and King's College London. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Research Ethics committee of King's College London gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.