417: Altered Sensitivity and Habituation in Chronic Pain: Sensitization and Predictive Coding Converge

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic primary musculoskeletal pain, Psychology, Pain in Special Populations , Imaging (e.g. fMRI, PET, MRS)

Background and Aims: Chronic pain is increasingly conceptualized as a disorder involving central sensitization and altered predictive processing. Central sensitization reflects amplified nociceptive signaling leading to greater sensitivity to stimuli, whereas predictive models indicate a potential disruption in prediction error processing when sensory inputs deviate from expectation. These mechanisms are not mutually exclusive and may jointly contribute to altered pain perception in chronic pain. Here, we examined whether chronic pain subjects differ from healthy controls in shock sensitivity and habituation, and whether psychological vulnerability measure moderate these processes.

Methods: Adults with chronic pain (CP) and healthy controls (HC) completed validated psychological measures and an fMRI cue-target shock paradigm involving repeated high and low intensity stimuli (approximately 130 trials per subject). Participants rated each stimulus on a 0-10 scale. Linear mixed-effects models predicted trial-by-trial pain ratings with a base model including: group, cue, shock condition, and trial sequence. Moderator models added one standardized questionnaire score at a time to assess their influence in rating patterns, with respect to group membership and shock condition. False discovery rate (FDR) correction was applied within predefined families of interaction terms (sensitivity and habituation families).

Results: CP participants demonstrated reduced differentiation between painful/nonpainful stimuli (group*shock,beta=-0.3,p<0.005). Higher baseline sensitivity (higher ratings to 4mA shock) significantly reduced the intensity discrimination within the CP group (group*shock*4mArating,beta=-1.3,p<0.001). CP also exhibited reduced habituation across trials (group*trial,beta=1.6,p<0.05). Psychological vulnerability measures significantly moderated group differences in shock level discrimination, where higher scores of negative affect and anxiety-related measures reduced sensory discrimination, surviving FDR correction (group*shock*moderator, all q<0.05). Of note, higher resilience scores in CP indicate stimuli difference more like HC’s (group*shock*resilience,beta=1.2,p<0.001).

Conclusions: CP was characterized by altered stimulus intensity encoding and reduced habituation to repeated noxious stimuli, consistent with combined central gain amplification and impaired predictive updating. Diminished difference between nonpainful and painful stimuli and higher ratings to the common 4mA shock indicate that shock levels were closer together in the CP group, with lower stimuli experienced as painful. Reduced habituation may reflect reduced ability to adjust internal models to filter out nonthreatening stimuli. Psychological factors shaped these alterations: increased negative affectivity measures amplified the reduced sensory discrimination, whereas resilience attenuated this pattern. Patients may benefit from cognitive-behavioral, exposure-based, or neuromodulatory interventions.

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Presenting Author: Rahwa Netsanet
Submitting Author: Rahwa Netsanet

Senior Author: Joshua Brown

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Rahwa Netsanet: B.S. - Indiana University
• Sisney Cheung: NA - Indiana University
• Sruthilatha Sakthi Velavan: B.S. - Marian University
• Mariah Evans: B.S. - Indiana Unviersity
• Kendall Moore: B.S. - Indiana University
• Joshua W. Brown: PhD - Indiana Unversity