Fear of pain and cortisol reactivity predict the strength of stress-induced hypoalgesia

I Timmers, A L Kaas, C W E M Quaedflieg, E E Biggs, T Smeets, J R de Jong, I Timmers, A L Kaas, C W E M Quaedflieg, E E Biggs, T Smeets, J R de Jong

Abstract

Background: Acute stress can have an effect on pain sensitivity, yet the direction of the effect - whether it is hypoalgesic or hyperalgesic - is mixed across studies. Moreover, which part of the stress response influences pain sensitivity is still unclear. In the current experimental study, we aim to examine the effect of acute stress on heat pain thresholds and pain tolerance levels in healthy participants, while taking into account individual differences in stress responses.

Methods: Forty-two healthy participants were randomly assigned to either a well-validated stress paradigm: the Maastricht Acute Stress Task (MAST; combining physical and psychological stressors) or to a nonstressful version of the task. Heat pain thresholds and tolerance levels were assessed at three times: prior to the MAST, immediately after the MAST during the presumed sympatho-adrenal medullary (SAM) response, and 15 min after MAST to cover the presumed hypothalamus-pituitary-adrenal (HPA) axis response. Stress responses were assessed both subjectively and physiologically.

Results: We observed that the acute stress induction led to increased heat pain thresholds, an effect that was present only in participants showing a cortisol response following stress induction and only in the presumed HPA axis time window. The strength of this hypoalgesic effect was further predicted by the change in cortisol and by fear of pain levels.

Conclusions: Our findings indicate that the HPA axis - and not the autonomic - stress response specifically underlies this stress-induced hypoalgesic effect, having important implications for clinical states with HPA axis dysfunctions.

Significance: This experimental study shows that an acute stress induction - that combines physical and psychological stressors - increases heat pain thresholds, but not tolerance in healthy participants. Furthermore, the magnitude of this stress-induced hypoalgesic effect is predicted by cortisol reactivity and fear of pain, revealing specific involvement of the HPA axis stress system and interactions with pain-related psychosocial aspects.

© 2018 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

Figures

Figure 1
Figure 1
Overview of the study procedure. The study procedure is presented plus the timing of the different measures and the presumed time windows for the two stress responses (SAM stress response in light grey; HPA axis stress response in dark grey). The thermometer with the thermode and response button (top) represents the pain threshold and tolerance measures. Note that for the analyses, baseline measures at t10 and t45 were averaged (tbaseline), except for blood pressure (MAP). MAST, Maastricht Acute Stress Task; PANAS, positive and negative affect schedule; SAM, sympatho‐adrenal medullary, HPA, hypothalamus–pituitary–adrenal.
Figure 2
Figure 2
Overview of the manipulation checks. Presented are (A) subjective stress measures, (B) autonomic measures [MAP, mean arterial pressure], and (C) cortisol measures. Significant effects are indicated with an asterisk (*p < 0.05) in the figure (black: main effects; in colour: specific group effect). Note that presumed time windows for the sympatho‐adrenal medullary (SAM) stress response (t55) and hypothalamus–pituitary–adrenal (HPA) axis stress response (t70) are highlighted by light and dark grey backgrounds, respectively.
Figure 3
Figure 3
Pain threshold and pain tolerance levels, per group. Presented are pain threshold and pain tolerance levels per group and per time point. Note that the main effect of time on pain thresholds was only significant in the stress group. Presented are estimated marginal means and standard errors (SE).
Figure 4
Figure 4
Correlations with the effect of stress on pain thresholds. Presented are correlations between the pain threshold difference t70–tbaseline and delta cortisol (A), fear of pain (B). Note that relevant statistics on outliers and influential cases has been checked.
Figure 5
Figure 5
Hypothalamus–pituitary–adrenal axis effects on pain threshold and pain tolerance levels. Presented are pain threshold and pain tolerance levels per cortisol responder group and per time point. Presented are estimated marginal means and standard errors (SE). Note that the main effect of time on pain thresholds was only significant in the cortisol responders, and not in both other groups.

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