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The following is a summary of “Nocebo Effect on Pain-Related Autonomic Responses in a State of Experimentally-Induced Sensitization,” published in the April 2025 issue of European Journal of Pain by Allmendinger et al. 

Heightened autonomic responses associated with pain were noted following induced secondary mechanical hyperalgesia (SMH) in both healthy individuals and various chronic pain groups, and stimulus-related autonomic responses could be altered by positive and negative expectations regarding the stimulus.  

Researchers conducted a retrospective study to analyze the impact of negative expectations on pain-related autonomic responses following experimentally induced SMH.  

They recruited 40 healthy participants (20 females), assigning them to either a NOCEBO or a NAÏVE group. Phasic skin conductance responses (SCR) and tonic background skin conductance levels (SCL) were recorded following 10 pinprick stimuli applied to both volar forearms, 1 arm (EXP-arm) received stimuli before (PRE) and after (POST), an experimental heat pain model to generate SMH, while the other arm served as the control (CTRL-arm). The NOCEBO group was informed that stimuli would be “more intense and painful” in the POST-assessment, while the NAÏVE group received no such instructions. Pain ratings were measured on a numeric rating scale (NRS) of 4 across all assessments to standardize subjective pain perception.  

The results showed that only the combination of induced SMH and negative expectation (i.e., EXP-arm in the NOCEBO group) significantly increased pinprick-evoked phasic SCRs (P < 0.001) from PRE to POST. Tonic background SCL increased from PRE to POST (P < 0.01), regardless of stimulation area (i.e., EXP-arm or CTRL-arm) or group (i.e., NOCEBO or NAÏVE).  

Investigators concluded that the findings indicated a facilitating influence of top-down modulatory processes, specifically negative expectations, on autonomic responses related to pain following experimentally induced SMH. 

Source: onlinelibrary.wiley.com/doi/10.1002/ejp.70029