Unravelling the neuropsychophysiological link between stress and pain : a protocol

Background: Stress has been suggested as an important contributing factor in the development and persistence of musculoskeletal pain but the underlying mechanisms between (dys)function of the major stress systems (i.e. the autonomic nervous system and the hypothalamus-pituitary-adrenal axis) and of pain sensitivity and pain processing remain unclear. Although stress and pain interactions may confer vulnerability to pain chronification, a comprehensive characterization of the multiple stress systems and their interactions with pain is lacking. Aims: The primary aim of this study is to characterize the stress system (dys)function (i.e., including basal levels, their reactivity and recovery to acute stress and chronic stress levels) in musculoskeletal pain groups with varying pain duration and extent, and to investigate the interaction between stress and pain at neuropsychophysiological level. The secondary aim is to define the contribution of stress to trajectories of pain, including chronification and recovery. Methods: A study with a cross-sectional and a longitudinal arm will be performed in musculoskeletal pain groups with varying pain characteristics, i.e. chronic widespread pain (fibromyalgia) and chronic as well as subacute localized pain (low back pain), and in pain-free controls (n=35/group). Localized pain groups will be reassessed after six months to characterize pain trajectories (recovered versus persisting). A mixture of neuropsychophysiological assessments will be used to assess stress and pain characteristics and functionality including questionnaires, autonomic measures (i.e., alpha-amylase, blood pressure, heart rate (variability), pre-ejection period, respiration rate, skin conductance and temperature), hormonal measures (i.e., cortisol and oxytocin), quantitative sensory testing (i.e., pain thresholds and pain tolerances, conditioned pain modulation and temporal summation of pain), and magnetic resonance imaging (brain activity). Discussion: The anticipated results will provide crucial insights on the role of stress in the extent of pain symptomatology and in conferring risk for pain chronicity and will shed light on the underlying neuropsychophysiological mechanisms of stress and pain interactions.