Background: Persistent idiopathic facial pain (PIFP) is a chronic disorder recurring daily for more than two hours per day over more than three months, in the absence of clinical neurological deficit. PIFP is the current terminology for Atypical Facial Pain and is characterized by daily or near daily pain that is initially confined but may subsequently spread. Pain cannot be attributed to any pathological process, although traumatic neuropathic mechanisms are suspected. When present intraorally, PIFP has been termed ‘Atypical Odontalgia’, and this entity is discussed in a separate article in this special issue. PIFP is often a difficult but important differential diagnosis among chronic facial pain syndromes. Aim: To summarize current knowledge on diagnostic criteria, differential diagnosis, pathophysiology and management of PIFP. Methods: We present a narrative review reporting current literature and personal experience. Additionally, we discuss and differentiate the common differential diagnoses associated with PIFP including traumatic trigeminal neuropathies, regional myofascial pain, atypical neurovascular pains and atypical trigeminal neuropathic pains. Results and conclusion: The underlying pathophysiology in PIFP is still enigmatic, however neuropathic mechanisms may be relevant. PIFP needs interdisciplinary collaboration to rule out and manage secondary causes, psychiatric comorbidities and other facial pain syndromes, particularly trigeminal neuralgia. Burden of disease and psychiatric comorbidity screening is recommended at an early stage of disease, and should be addressed in the management plan. Future research is needed to establish clear diagnostic criteria and treatment strategies based on clinical findings and individual pathophysiology.

We conducted a cross-sectional study to re-examine the clinical profile of patients with a clinical diagnosis of classical trigeminal neuralgia (CTN). Inclusion criteria consisted of the International Headache Society’s published classification of CTN. For the specific purposes of the study, features such as autonomic signs, persistent background pain, attack durations of >2 minutes and reports of pain-related awakening were included. The demographic and clinical phenotype of each patient were carefully recorded for analysis. The study cohort consisted of 81 patients and based on reported attack duration these were divided into short (≤ 2 minutes, n = 61) and long (> 2 minutes, n = 20) groups for further analysis. The group with short attack duration neatly fit most of the criteria for CTN while the long attack group presents a more challenging diagnosis. There were no significant differences in pain severity, quality and location between the short and long attack groups. The frequency of persistent background pain was significantly higher in the long (70%) compared to the short attack group (29.5%, p = 0.001). There were significantly more reports of pain-related awakenings in the long (55%) than in the short attack groups (29.5%, p = 0.04). There were no significant differences in the frequency of autonomic signs between the short (21.3%) and long attack groups (40%, p = 0.1). In the short attack group, the presence of autonomic signs was significantly associated with longer disease duration, increased pain-related awakenings, and a reduced prognosis. There are clear diagnostic criteria for CTN but often patients present with features, such as long pain attacks, that challenge such accepted criteria. In our cohort the clinical phenotype of trigeminal, neuralgiform pain with or without autonomic signs and background pain was observed across both short and long attack groups and the clinical implications of this are discussed.

Background: The dorsal root (DRG) and trigeminal (TG) ganglia contain cell bodies of sensory neurons of spinal and trigeminal systems, respectively. They are homologs of each other; however, differences in how the two systems respond to injury exist. Trigeminal nerve injuries rarely result in chronic neuropathic pain (NP). To date, no genes involved in the differential response to nerve injury between the two systems have been identified. We examined transcriptional changes involved in the development of trigeminal and spinal NP.Methods: Trigeminal and spinal mononueropathies were induced by chronic constriction injury to the infraorbital or sciatic nerve. Expression levels of 84 genes in the TG and DRG at 4, 8 and 21 days post‐injury were measured using real‐time PCR.Results: We found time‐dependent and ganglion‐specific transcriptional regulation that may contribute to the development of corresponding neuropathies. Among genes significantly regulated in both ganglia Cnr2, Grm5, Htr1a, Il10, Oprd1, Pdyn, Prok2 and Tacr1 were up‐regulated in the TG but down‐regulated in the DRG at 4 days post‐injury; at 21 days post‐injury, Adora1, Cd200, Comt, Maob, Mapk3, P2rx4, Ptger1, Tnf and Slc6a2 were significantly up‐regulated in the TG but down‐regulated in the DRG.Conclusions: Our findings suggest that spinal and trigeminal neuropathies due to trauma are differentially regulated. Subtle but important differences between the two ganglia may affect NP development.Significance: We present distinct transcriptional alterations in the TG and DRG that may contribute to differences observed in the corresponding mononeuropathies. Since the trigeminal system seems more resistant to developing NP following trauma our findings lay ground for future research to detect genes and pathways that may act in a protective or facilitatory manner. These may be novel and important therapeutic targets.