Nocebo Effect on Pain‐Related Autonomic Responses in a State of Experimentally‐Induced Sensitization
Bibliographic record
Abstract
BACKGROUND: Enhanced pain-related autonomic responses were reported after experimentally-induced secondary mechanical hyperalgesia (SMH) in healthy individuals as well as in a variety of chronic pain cohorts. Stimulus-induced autonomic responses can also be modulated by positive and negative expectations towards the applied stimulus. This study aimed to investigate the influence of negative expectations on pain-related autonomic responses after experimentally-induced SMH. METHODS: Forty healthy participants (20 females) were recruited and assigned to a NOCEBO or a NAïVE group. Phasic skin conductance responses (SCR) and tonic background skin conductance level (SCL) were recorded in response to 10 pinprick stimuli applied to both volar forearms. On one arm, all stimuli were applied (EXP-arm) before (PRE) and after (POST) an experimental heat pain model to induce SMH. The other arm served as the control (CTRL-arm). The NOCEBO group was instructed that the stimuli will be 'more intense and painful' in the POST-assessment. The NAïVE group did not receive any instructions. Pain ratings were matched to a numeric rating scale 4 across all assessments to control for subjective pain perception. RESULTS: Only the combination of induced SMH and negative expectation (i.e., EXP-arm in the NOCEBO group) increased the pinprick-evoked phasic SCRs (p < 0.001) from PRE to POST. Tonic background SCL increased from PRE to POST (p < 0.01) independent of stimulation area (i.e., EXP-arm or CTRL-arm) or group (i.e., NOCEBO or NAïVE). CONCLUSIONS: These results demonstrate facilitatory effects of top-down modulatory processes (i.e., negative expectations) on pain-related autonomic responses after experimentally-induced SMH. SIGNIFICANCE: This study showed a facilitatory effect of negative expectation on enhanced pain-related autonomic responses in a state of experimentally-induced sensitisation in healthy participants. Hence, pain-related autonomic responses are shaped by both bottom-up (nociceptive input) and top-down (expectation) modulatory processes. This leads to the clinical implication that increased pain-related autonomic responses reported in individuals with chronic pain might not solely reflect pain hypersensitivities through nociceptive sensitisation, but also exaggerated negative expectation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".