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Suter, M. R.

Publications and source records attributed to Suter, M. R..

2 recordsLinked to original sources

Simulating a medical expertise: a robust novel stress induction paradigm in chronic pain patients

Maladaptive stress responses may exacerbate chronic widespread pain (CWP) and deserve further investigations. Yet, existing stress induction paradigms lack relevance for individuals with this condition. Hence, we developed the Social Benefits Stress Test (SBST), adapted from the Trier Social Stress Test. Instead of a job interview, the main task consists in justifying the inability to work. Forty women with CWP in the context of hypermobile Ehlers-Danlos syndrome or hypermobility spectrum disorders were included. They underwent a 30-min baseline, the new stress task and a recovery period. The psychophysiological stress response was captured using self-reported stress ratings, salivary cortisol and - amylase levels, as well as continuous physiological monitoring of heart rate variability (HRV) and electrodermal activity (EDA). Compared to baseline, the analysis revealed a significant and transient increase in stress ratings during the stress task, associated with a peak in salivary biomarkers concentrations. The HRV signal analysis showed a significant decrease in high frequency power (HF), and increases in heart rate, low frequency power (LF) and in LF/HF ratio. The EDA analysis revealed a significant increase in skin conductance level (SCL) tonic component and skin conductance response (SCR). Subjective stress ratings positively correlated with changes in salivary biomarkers, LF/HF ratio and EDA outcomes. The SBST induced a reproducible moderate stress response across subjective and physiological measures in a population of CWP patients, validating this task as a relevant experimental model of social stress in chronic pain. The SBST is a useful tool to study the relationship between stress and chronic pain. PerspectiveThis manuscript presents the Social Benefits Stress Test (SBST) as a novel paradigm to assess stress reactivity in chronic widespread pain patients. By simulating the challenge of justifying work incapacity, it elicits a reproducible stress response, supporting its use as a model to study stress-pain interactions and evaluate therapeutic interventions.

neuroscience↗

Kir2.1 modulation in macrophages sensitises dorsal root ganglion neurons through TNF secretion after nerve injury

Macrophages and satellite glial cells are found between injured and uninjured neurons in the lumbar dorsal root ganglia (DRG). We explored the mechanism of neuro-immune and neuron-glia crosstalk leading to hyperexcitability of DRG neurons. After spared nerve injury (SNI), CX3CR1+ resident macrophages became activated, proliferated and increased inward-rectifying potassium channel Kir2.1 currents. Conditioned medium (CM) by macrophages, obtained from DRG of SNI mice, sensitised small DRG neurons from naive mice. However, treatment with CM from GFAP+ glial cells did not affect neuronal excitability. When subjected to this macrophage-derived CM, DRG neurons had increased spontaneous activity, current-evoked responses and voltage-gated NaV1.7 and NaV1.8 currents. Silencing Kir2.1 in macrophages after SNI prevented the induction of neuronal hyperexcitability from their CM. Blocking vesicular exocytosis or soluble tumour necrosis factor (TNF) in CM or interfering with the downstream intracellular p38 pathway in neurons, also prevented neuronal hyperexcitability. Blocking protein trafficking in neurons reduced the effect of CM, suggesting that the hyperexcitable state resulted from changes in NaV channel trafficking. These results suggest that DRG macrophages, primed by peripheral nerve injury, contribute to neuron-glia crosstalk, NaV channel dysregulation and neuronal hyperexcitability implicated in the development of neuropathic pain. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=87 SRC="FIGDIR/small/545843v2_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@2591acorg.highwire.dtl.DTLVardef@7ebc82org.highwire.dtl.DTLVardef@8a2c4corg.highwire.dtl.DTLVardef@1624244_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗