Deciphering Persistent Orofacial Pain - Persistent Idiopathic Facial Pain

Background and Rationale:

Persistent non-dental orofacial pain is common but poorly understood, and its underlying pathophysiology remains largely undefined. Two clinically similar entities can be distinguished. Painful post-traumatic trigeminal neuropathy (PTNP) is characterized by persistent pain accompanied by demonstrable somatosensory changes (negative signs such as hypoesthesia and hypoalgesia, and/or positive signs such as allodynia and hyperalgesia) in the painful area, typically following nerve injury. Persistent idiopathic facial pain (PIFP; formerly "atypical facial pain") is a constant, dull, poorly localized facial pain that does not follow the distribution of a single trigeminal branch, may cross the midline over time, and is not associated with a neuralgiform pain component; clinical and radiographic examinations are unremarkable. Because the two conditions are clinically nearly identical, patients frequently attribute the pain to dental causes, and unnecessary dental treatment or tooth extraction can aggravate and chronify the pain.

The absence of somatosensory deficits in PIFP suggests that altered central processing of trigeminal nociceptive input, rather than a purely peripheral mechanism, contributes to the pain. This is consistent with the concept of nociplastic pain, in which centrally altered sensory processing and pain modulation drive an augmented pain response. Prior high-resolution brainstem functional MRI (fMRI) work demonstrated that PIFP patients show stronger activation of the spinal trigeminal nucleus in response to standardized trigeminal nociceptive stimulation compared with healthy controls. However, fMRI alone cannot distinguish central sensitization (top-down) from a peripheral drive maintained by ongoing nociceptor input. This study therefore combines quantitative sensory testing (QST) with a trigemino-nociceptive fMRI paradigm that incorporates a peripheral nerve block, in order to characterize the peripheral and central contributions to PIFP.

Objectives and Hypotheses:

The overarching objective is to describe and characterize the pathophysiology of PIFP by comparing PIFP patients with age- and sex-matched healthy controls using non-invasive psychophysical and neuroimaging methods. The central hypothesis is that PIFP patients exhibit a disturbance of central trigeminal nociceptive processing at the brainstem level and in other critical trigeminal pain-processing regions, such as the thalamus and insula, that distinguishes them from healthy controls. A secondary hypothesis is that, within PIFP patients, a peripheral anesthetic nerve block will separate individuals whose pain is driven peripherally (pain abolished during the block) from those whose pain is maintained centrally/nociplastically (pain persists despite cutaneous numbness), and that these subgroups differ in their central nociceptive processing.