An Innovative Cognitive-Behavioral Treatment For Chronic Orofacial Pain

NCT07123233 | Recruiting

• 2 other identifiers: FACE-PRTGR2024
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Use these resources to provide understandable information about this study to patients, families, and health care providers: The present randomized clinical trial (RCT), conducted at the IRCCS Carlo Besta Neurological Institute, aims to evaluate the effectiveness of Pain Reprocessing Therapy (PRT), a form of psychological support/psychotherapy based on cognitive-behavioral therapy, which has already proven effective in the treatment of other types of primary chronic pain. Chronic Primary Orofacial Pain (CPOP) is a rare and complex form of chronic pain that predominantly affects adult women and occurs without evident lesions, yet has a significant emotional and functional impact. It was recently classified among chronic primary pain conditions in the ICD-11 and is considered a form of nociplastic pain, associated with alterations in brain connectivity. At present, pharmacological treatments have shown limited effectiveness. This randomized clinical trial (RCT), conducted at the IRCCS Carlo Besta Neurological Institute, aims to evaluate the effectiveness of Pain Reprocessing Therapy (PRT), a form of psychological support/psychotherapy based on cognitive-behavioral therapy, which has already proven effective in the treatment of other types of primary chronic pain. Sixty participants, all diagnosed with CPOP according to ICD-11 criteria, will be selected and randomly assigned to two groups: one will receive PRT, the other will receive treatment as usual (TAU). The primary outcome of the study is the assessment of pain intensity reduction. Secondary outcomes include a broad range of psychosocial variables: improvement in quality of life, reduction of anxiety-depressive symptoms, catastrophizing, and other psychopathological traits. The effects of the therapy on brain connectivity will also be analyzed using fMRI, and on pain neurophysiology through the Conditioned Pain Modulation (CPM) paradigm. The protocol provides for the evaluation of therapy effectiveness at three follow-ups (3, 6, and 12 months) in order to measure the duration of effects. Finally, through advanced statistical analysis tools and the support of artificial intelligence, the study also aims to identify specific clinical-neurofunctional profiles that may be useful for differential diagnosis and for tailoring therapeutic interventions.

Conditions

Persistent Idiopathic Facial Pain (PIFP); Chronic Primary Orofacial Pain (CPOP)

Keywords

Cognitive-behavioral therapy; Pain-Reprocessing Therapy; Chronic Primary Orofacial pain; chronic pain; chronic primary pain; nociplastic pain

Outcome Measures

Primary Outcomes (1)

• Average pain intensity over the past week.

  Average pain intensity over the past week, measured using the Brief Pain Inventory-Short Form (BPI-SF). Score range: 0-10, with higher scores indicating greater pain intensity (worse outcome).

  12 months

Secondary Outcomes (4)

• Quality of life (EUROHIS-8)

  12 months

• Depressive and anxiety symptoms (BDI-II, BAI)

  12 months

• Catastrophism (PCS)

  12 months

• Psychopathology (MCMI-III)

  12 months

Study Arms (2)

PRT-TAU

EXPERIMENTAL

Patients will attend 8 sessions of PRT treatments while undergoing their usual pharmacological treatment

Behavioral: Pain Reprocessing Therapy

TAU

PLACEBO COMPARATOR

Patients will undergo the usual pharmacological treatment.

Behavioral: Usual Therapy

Interventions

Usual Therapy BEHAVIORAL

Patients undergo yhe usual pharmacological tretment as prescrived by neurologist

TAU

Pain Reprocessing Therapy BEHAVIORAL

One cohort of 30 patients (PRT+TAU group) will receive eight sessions of Pain Reprocessing Therapy (PRT) in addition to Treatment-as-Usual (TAU). PRT is a cognitive-behavioral-inspired approach aimed at helping patients reinterpret chronic pain as brain-generated rather than structurally caused. A second cohort of 30 patients (TAU group) will undergo the same assessment phases but will receive only Treatment-as-Usual without PRT. Use this module to add a description of each group or cohort in the study and to list any interventions of interest.

PRT-TAU

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Chronic Primary Orofacial Pain (CPOP) according to ICD-11 criteria.
• Written informed consent.
• Age 18 years or older.

You may not qualify if:

• Age over 70 years.
• Current use of immunosuppressive medications (e.g., steroids).
• History of cancer (breast, thyroid, prostate, blood cancers, etc.).
• History of stroke, neurosurgical interventions, or brain tumors.
• History of specific inflammatory diseases (lupus, scleroderma, rheumatoid arthritis, polymyalgia rheumatica).
• History of psychiatric disorders such as schizophrenia, personality disorders, dissociative identity disorder, or other severe psychoses.
• Unexpected or unintentional weight loss of 10 kg or more in the year prior to recruitment.
• Difficulty participating due to logistical problems.
• Contraindications to undergoing functional magnetic resonance imaging (fMRI).
• Psychotherapy treatment of any kind within 15 months prior to the assessment date.

Sponsors & Collaborators

• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: lead

Study Sites (1)

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, 20133, Italy

RECRUITING

Related Publications (6)

• Schmidt S, Muhlan H, Power M. The EUROHIS-QOL 8-item index: psychometric results of a cross-cultural field study. Eur J Public Health. 2006 Aug;16(4):420-8. doi: 10.1093/eurpub/cki155. Epub 2005 Sep 1.

  PMID: 16141303 BACKGROUND

• Monticone M, Baiardi P, Ferrari S, Foti C, Mugnai R, Pillastrini P, Rocca B, Vanti C. Development of the Italian version of the Pain Catastrophising Scale (PCS-I): cross-cultural adaptation, factor analysis, reliability, validity and sensitivity to change. Qual Life Res. 2012 Aug;21(6):1045-50. doi: 10.1007/s11136-011-0007-4. Epub 2011 Sep 13.

  PMID: 21912846 BACKGROUND

• Benoliel R, Svensson P, Evers S, Wang SJ, Barke A, Korwisi B, Rief W, Treede RD; IASP Taskforce for the Classification of Chronic Pain. The IASP classification of chronic pain for ICD-11: chronic secondary headache or orofacial pain. Pain. 2019 Jan;160(1):60-68. doi: 10.1097/j.pain.0000000000001435.

  PMID: 30586072 BACKGROUND

• Ashar YK, Gordon A, Schubiner H, Uipi C, Knight K, Anderson Z, Carlisle J, Polisky L, Geuter S, Flood TF, Kragel PA, Dimidjian S, Lumley MA, Wager TD. Effect of Pain Reprocessing Therapy vs Placebo and Usual Care for Patients With Chronic Back Pain: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Jan 1;79(1):13-23. doi: 10.1001/jamapsychiatry.2021.2669.

  PMID: 34586357 BACKGROUND

• Benoliel R, Gaul C. Persistent idiopathic facial pain. Cephalalgia. 2017 Jun;37(7):680-691. doi: 10.1177/0333102417706349. Epub 2017 Apr 20.

  PMID: 28425324 BACKGROUND

• Nicholas M, Vlaeyen JWS, Rief W, Barke A, Aziz Q, Benoliel R, Cohen M, Evers S, Giamberardino MA, Goebel A, Korwisi B, Perrot S, Svensson P, Wang SJ, Treede RD; IASP Taskforce for the Classification of Chronic Pain. The IASP classification of chronic pain for ICD-11: chronic primary pain. Pain. 2019 Jan;160(1):28-37. doi: 10.1097/j.pain.0000000000001390.

  PMID: 30586068 BACKGROUND

MeSH Terms

Conditions

Chronic Pain; Nociplastic Pain

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Licia Grazzi, MD

  Fondazione IRCCS Istituto Neurologico Carlo Besta

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Licia Grazzi, MD

CONTACT

+ 39 02.2394; licia.grazzi@istituto-besta.it

Alessandra Telesca, phd

CONTACT

alessandra.telesca@istituto-besta.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2025
• First Posted: August 14, 2025
• Study Start: September 24, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: February 11, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)