211: Biopsychosocial phenotypes of CPSP: physical activity, biomarkers and cortical activity

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic postsurgical pain, Pain in Special Populations , Imaging (e.g. fMRI, PET, MRS), Pain in special populations (e.g. neonates, children, teens, elderly, neurodegenerative diseases)

Background and Aims: Although chronic postsurgical pain (CPSP) in adolescents and young adults (AYAs) is increasingly recognized as a heterogeneous
condition, existing studies have largely examined psychological, physiological, or neurobiological factors in isolation. Critically, no prior work has integrated
objective physical performance with stress biomarkers and resting-state cortical hemodynamics to identify biopsychosocial phenotypes of CPSP in this
population. Based on these considerations, the aim of this study was to identify biopsychosocial phenotypes of physical performance using a clustering approach
that integrates pain interference, psychological symptoms, physical fitness, hair cortisol concentration, and resting state cortical hemodynamic activity in AYAs
with CPSP.

Methods: This observational cross-sectional study included AYAs aged 18–30 years with CPSP persisting ≥ 3 months after surgery. Self-reported measures
assessed pain interference, anxiety (both assessed by PROMIS measures) and pain catastrophizing (PCS). Physical performance was evaluated using a 1-
minute sit-to-stand (1-STS) test with heart rate and oxygen saturation. Chronic stress was measured via hair cortisol concentration. Resting-state cortical
hemodynamic activity was assessed during a 10-minute functional near-infrared spectroscopy (fNIRS) assessment. Unsupervised hierarchical clustering (Ward’s
method) identified biopsychosocial phenotypes, which were compared across psychological, physiological, stress, and fNIRS measures, excluding sit-to-stand variables to avoid circularity.

Results: Thirty-two individuals with CPSP (70% female; mean age = 25.4 years) were included. Based on 1-STS performance, two functional phenotypes
emerged: lower-functioning (n = 8) and higher-functioning (n = 24). Groups did not differ in age, sex, or race (all p > 0.05). The lower-functioning phenotype
showed higher pain catastrophizing (p = 0.029), higher cardiovascular reactivity during exertion (p = 0.001), and increased resting-state functional connectivity
between left and right lateral prefrontal cortices (p = 0.034) and between the right lateral prefrontal and contralateral sensorimotor cortices (p = 0.047).

Conclusions: A clustering approach based on physical performance identified two distinct biopsychosocial phenotypes among AYAs with CPSP. The
lower-functioning phenotype was characterized by greater pain catastrophizing, heightened cardiovascular reactivity during exertion, and increased resting-state
prefrontal and fronto–sensorimotor connectivity, independent of sociodemographic factors. These findings suggest that physical performance
captures meaningful heterogeneity in CPSP, linking functional capacity with cognitive–emotional burden, autonomic responsivity, and neurophysiological
organization. Performance-based phenotyping may support more targeted assessment and intervention strategies in AYAs with CPSP.

References: 1-Ceniza-Bordallo G, Fraile AG, López-de-Uralde-Villanueva I, Rabbitts JA, Li R, Palermo TM, Martín-Casas P. Chronic postsurgical pain in young children: Prevalence, pain trajectories and physical and psychological prognostic factors. J Pain. 2025 Sep;34:105476. doi: 10.1016/j.jpain.2025.105476. Epub 2025 Jun 23. PMID: 40562263; PMCID: PMC12282272.
2-Ceniza-Bordallo G, Gómez Fraile A, Martín-Casas P, Rabbitts JA, Li R, Palermo TM, López-de-Uralde-Villanueva I. Prevalence, pain trajectories, and presurgical predictors for chronic postsurgical pain in a pediatric sample in Spain with a 24-month follow-up. Pain. 2025 Jan 1;166(1):112-122. doi: 10.1097/j.pain.0000000000003330. Epub 2024 Jul 10. PMID: 39047258; PMCID: PMC11856900.
3-Roman-Juan J, Ceniza-Bordallo G, Sánchez-Rodríguez E, Jensen MP, Miró J. Fatigue, sleep disturbance, and pain interference in children and adolescents with chronic pain: a longitudinal study. Pain. 2025 Apr 1;166(4):927-935. doi: 10.1097/j.pain.0000000000003432. Epub 2024 Oct 30. PMID: 39480238.
4-Ceniza-Bordallo G, Simons LE, Martín-Casas P, Sieberg CB. Long-term predictive validity of the Pediatric Pain Screening Tool for chronic postsurgical pain and pain-related quality of life impairment: associations with risk stratification groups in Spain. J Pain. 2026 Feb 11:106221. doi: 10.1016/j.jpain.2026.106221. Epub ahead of print. PMID: 41687701.
5-Ceniza-Bordallo G, Gómez Fraile A, Martín-Casas P, López-de-Uralde-Villanueva I. Validation of the Spanish version of the Pain Catastrophizing Scale for Children (PCS-C). An Pediatr (Engl Ed). 2023 Nov;99(5):295-303. doi: 10.1016/j.anpede.2023.09.011. Epub 2023 Oct 25. PMID: 37891137.
6-Ceniza-Bordallo G, Fraile AG, Martín-Casas P, López-de-Uralde-Villanueva I. Validity and reliability of Spanish PROMIS pediatric pain interference short form. J Pediatr Nurs. 2022 Sep-Oct;66:79-85. doi: 10.1016/j.pedn.2022.05.015. Epub 2022 Jun 7. PMID: 35687928.
7-Ceniza-Bordallo G, Gómez Fraile A, Martín-Casas P, López-de-Uralde-Villanueva I. Cross-cultural adaptation and psychometric properties of Spanish Child Pain Anxiety Symptoms Scale. An Pediatr (Engl Ed). 2023 Jul;99(1):14-25. doi: 10.1016/j.anpede.2023.06.003. Epub 2023 Jun 7. PMID: 37290986.

Presenting Author: Guillermo Ceniza-Bordallo
Submitting Author: Guillermo Ceniza-Bordallo

Senior Author: Christine B Sieberg

IASP 2026 Global Year theme of Neuropathic Pain: No

• Guillermo Ceniza-Bordallo: PhD - Center for Health Outcomes and Interdisciplinary Research, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
• Ziyan Wu: PhD - Center for Health Outcomes and Interdisciplinary Research, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
• Caitlin Curry - Center for Health Outcomes and Interdisciplinary Research, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA.
• Christine B Sieberg: PhD - Center for Health Outcomes and Interdisciplinary Research, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA. Division of Adolescent and Young Adult Medicine, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.