Deciphering Persistent Orofacial Pain - PIFP

NCT07791004 | Not Yet Recruiting

• 1 other identifier: 2024-101254-BO-ff-PIFP
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Persistent non-dental orofacial pain is common yet poorly characterised, and its pathophysiology remains largely unknown. Two clinically similar entities are distinguished: post-traumatic trigeminal neuropathic pain (PTNP), in which peripheral nerve damage is demonstrable, and persistent idiopathic facial pain (PIFP), in which peripheral findings are typically absent - pointing to an altered central processing of trigeminal nociceptive input. This monocentric study characterises the peripheral and central mechanisms of PIFP by comparing PIFP patients with age- and sex-matched healthy controls using a combination of non-invasive peripheral and central approaches. The study comprises two work packages. The peripheral work package uses quantitative sensory testing (standardised DFNS protocol) to test the hypothesis that PIFP patients retain an intact peripheral nervous system. The central work package uses functional MRI with standardised trigemino-nociceptive stimulation to characterise brainstem network dynamics, testing the hypothesis that PIFP patients exhibit a central trigeminal processing disturbance at the brainstem level. In PIFP patients, the functional MRI is repeated before and after a local-anaesthetic nerve block in the pain area, additionally distinguishing patients whose pain is completely abolished by the block from those with persistent pain despite it. The overarching aim is to characterise the pathophysiological basis of PIFP and thereby advance the mechanistic understanding of persistent orofacial pain.

Conditions

Persistent Idiopathic Facial Pain (PIFP)

Keywords

PIFP; fMRI; atypical facial pain; nerve block; local anesthesia

Outcome Measures

Primary Outcomes (2)

• Difference in brain functional neuroimaging response to standardized trigemino-nociceptive stimulation between PIFP patients HC

  BOLD signal change (contrast estimates, arbitrary units) during standardized trigemino-nociceptive stimulation versus baseline, compared between PIFP patients and HC in a priori defined regions of interest and at whole-brain level.

  Baseline (MRI session before local anesthesia)

• Difference in brain activation before versus after the local-anesthetic nerve block, and between complete responders and non-responders

  BOLD signal change (contrast estimates, arbitrary units) during standardized trigemino-nociceptive stimulation, compared within participants before versus after the local-anesthetic nerve block, and between participants whose pain is completely abolished by the block and those with persistent pain despite the block

  Pre-block MRI at baseline and post-block MRI, both on the same day 1

Secondary Outcomes (1)

• Comparison of deep phenotyping and quantitative sensory testing (QST) parameters between the study cohorts (PIFP versus HC).

  Baseline (single assessment before local anesthesia)

Study Arms (2)

Patients with persistent idiopathic facial pain (PIFP)

Patients with persistent idiopathic facial pain

Age- and sex-matched healthy controls (HC)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with PIFP will be recruited from the headache/facial pain outpatient clinic of the University Medical Center Hamburg-Eppendorf

You may qualify if:

• Healthy controls: written informed consent.
• PIFP cohort: written informed consent, and a diagnosis of PIFP according to the ICHD-3 and ICOP diagnostic criteria.

You may not qualify if:

• Contraindication to MR scanning
• Anxiety disorders, including claustrophobia
• Other somatic diseases, including other pain disorders
• Other primary headache disorders and medication-overuse headache
• Skin lesion , infection, or scarring at the stimulation sites preventing safe electrode placement
• Healthy volunteers: any history of persistent pain or primary headache, including in first-degree relatives
• History of psychiatric disease and/or addiction
• Pregnancy or lactation
• Any regular medication; in PIFP patients, occasional acute analgesic use (NSAID, fewer than 8 days per month) is permitted
• Use of acute analgesic within 24 hours before the experiment

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead

Study Sites (1)

University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Related Publications (3)

• Ziegeler C, Schulte LH, May A. Altered trigeminal pain processing on brainstem level in persistent idiopathic facial pain. Pain. 2021 May 1;162(5):1374-1378. doi: 10.1097/j.pain.0000000000002126.

  PMID: 33110030 BACKGROUND

• Mehnert J, Basedau H, Sturm LM, Nielsen T, Jensen RH, May A. Functional brainstem representations of the human trigeminal cervical complex. Cephalalgia. 2023 May;43(5):3331024231174862. doi: 10.1177/03331024231174862.

  PMID: 37203351 BACKGROUND

• May A, Ciancia V, Basedau H. Visualizing nociplastic pain: functional hyperexcitability in neuropathic and idiopathic facial pain syndromes. J Headache Pain. 2025 Oct 13;26(1):211. doi: 10.1186/s10194-025-02133-w.

  PMID: 41083924 BACKGROUND

Study Officials

• Arne May, MD, PhD

  Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arne May, MD, PhD

CONTACT

+49 40 74105 9189; a.may@uke.de

Kuan-Po Peng, MD

CONTACT

+49 40 74102 7305; k.peng@uke.de

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Associate

Study Record Dates

• First Submitted: August 18, 2026
• First Posted: August 27, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): October 31, 2029
• Last Updated: August 27, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)