Given that neurovascular compression plays a role in some forms of TN, it would seem probable that arterial tortuosity and hypertension could increase the risk of having TN. In a small cohort of 36 patients in Minnesota, Yoshimasu et al. [32] reported a possible association with hypertension, with an odds ratio of 1.96 (95 % confidence interval 1.2–3.1). There are, however, conflicting reports in the literature. Teruel [33] used a hospital population of 84 classic TN with and without hypertension (diagnosed and treated with antihypertensives by physicians) and compared them to 252 age- and gender-matched controls. They found a prevalence of 37 % in TN and 32 % in the control group with an odds ratio of 1.24 (95 % confidence interval 0.7–2) which was not statistically significant when compared to the controls. It needs to be noted that this was a retrospective study, the duration of hypertension may be important and it could be that both populations are older. A population study based on insurance claims which cover 97 % of the population in Taiwan showed that patients with hypertension have an increased risk of getting TN [34]. Pan et al. [34] identified 138,492 people with at least two visits of ICD9-coded hypertensive diagnosis and then found 2 age- and sex-matched subjects for each, thus making 276,984 patients. A diagnosis of TN had to be recorded at least twice, and they also ascertained the presence of diabetes and hyperlipidaemia as comorbidities over a 3-year period. They identified 121 patients who developed TN in the hypertensive group and 167 in the non-hypertensive group and when corrected for the comorbidities had an adjusted hazard ratio of 1.5 (95 % CI 1.19–1.9). The follow-up was only 3 years, so the effect of duration of hypertension was not evaluated. A longer-term follow-up would ascertain whether hypertension results in increased tortuosity of vessels, which could then produce demyelination of the trigeminal nerve if in close contact. An epidemiological study in a city of Egypt looking for TN in >30-year-olds found 4 cases among 13,541 and noted comorbid depression and hypertension [35]. The cases were diagnosed by experienced neurologists.

In a prospective cohort of 158 patients, a history of hypertension was found in 32 % (95 % confidence intervals, 25–40 %), and 17 % had some form of cardiovascular disease, but this data was not compared to controls or national data [36].

Using the same insurance database in Taiwan as described for hypertension, Pan et al. [37] looked for increased susceptibility to stroke. They identified 1453 TN patients (based on at least 3 visits over a 2-year period) and then for the same time period examined a non-TN age- and gender-matched group of 5812 individuals. They reported an increased risk of stroke after TN was diagnosed (TN cohort, 73 developed a stroke), and so the adjusted (controlled for other cardiovascular disorders and diabetes) hazard ratio was 1.76 (95 % CI 1.33–2.33). However, other risk factors are not accounted for, the study only lasted 2 years and there are no details of how the diagnosis was made.

It would be expected that these patients may have other forms of headache, and in the 158 patients reported by Maarbjerg [36], the following were noted: tension-type headache 13 %, migraine without aura 9 %, post-traumatic headache 3 %, idiopathic stabbing headache 1 % and cluster headache 1 %. Association of cluster headache and TN has been described by several headache neurologists and termed Cluster-tic [38]. Haviv et al. [39] in their study of 81 TN patients reported no significant association with muscle pain but did note disturbance of sleep. Although most patients report that sleep provides a welcome relief from TN, Wu et al. have shown that sleep disturbance is more likely in TN and other studies have confirmed this finding [39, 40]. Glossopharyngeal neuralgia and TN can coexist. Gaul et al. reported 2 cases in 19 patients [41] and Ferroli reported 6 out of 31 [42].

As with all chronic pains, psychological factors need to be considered, and it is often difficult to differentiate between pre-existing psychiatric and psychological problems and those arising as a result of the pain itself or due to the medications. Several anticonvulsants are also used in psychiatric practice and so could possibly mask some psychiatric disorders [43].

The largest study to date looking at the relationship between TN and mental health was reported by Wu et al. in 2015 [43]. Using the national database over a period of 10 years, they compared newly diagnosed TN patients with no previous psychiatric problems (n. 3273), with a matched control group of 13,092. The diagnosis of TN had been made by a neurologist based on at least two visits and the mental health diagnosis by a psychiatrist. They found TN patients had increased depression, anxiety and sleep disturbance but no other psychosis. Previous smaller studies have suggested similar findings, but in those studies, TN patients were compared to other facial pain patients. Castro et al. [44] compared 15 TN patients with 15 temporomandibular patients in a secondary care setting using semi-directed interviews and the Hospital Anxiety and Depression Scale (HADS). Both groups showed mild anxiety and depression with high limitations in activities of daily living, although it was only the TN patients that reported high pain intensity. Patients with TN appeared to have better coping strategies and were more positive about outcomes. Graff-Radford et al. [45] highlighted that there was higher psychological dysfunction (Minnesota Multiphasic Inventory and Chronic Illness Problem Inventory) in 21 patients with postherpetic neuralgia than 15 TN. They postulate that despite TN pain being of greater severity, it was intermittent, so providing a period of respite.

A group of 30 TN and TN+ concomitant pain patients were compared to 30 persistent idiopathic facial pain using the following measures: Sheehan Disability Scale (assessment of the patients’ functional impairment in three domains: work/school, social life/leisure activities and family life/home responsibilities score >5 impairment), Covi Anxiety Scale and Beck Depression Inventory (BDI). The TN group showed significantly higher scores for physical disability, anxiety and depression than the persistent idiopathic facial pain group [46]. Unlike the Castro study, anxiety and depression were linked with pain severity, especially in those with TN and concomitant pain [46]. This could support Graff-Radford’s theory that it is the continuous nature of chronic pain that is more likely to result in psychological morbidity. This is further supported by Komiyama et al. study [47], which compared 282 burning mouth syndrome patients and 83 TN. In this study patients in both groups were divided into those with acute (<6 months) and chronic (>6 months) symptoms, and they used the questionnaires from the Research Diagnostic Criteria for Temporomandibular Disorders (RDC-TMD) Axis II section. Pain severity was higher in both acute and chronic TN than in burning mouth syndrome patients, but somatization and depression were lower.

Zakrzewska and Thomas [48], using the Hospital Anxiety and Depression Scale (HADS), showed that depression reduced significantly after surgical management with radiofrequency thermocoagulation, whereas there was a less significant reduction of anxiety.

More formal neuropsychological assessments do show that patients with TN have deficits in psychomotor speed, reaction time, complex attention and cognitive flexibility as well as cognitive memory and general cognitive functioning, but it is difficult to determine what accounts for this, pain, medications or disease-specific features [49]. A recent study looking at adverse effects of antiepileptics in TN using questionnaires shows that cognitive function is significantly affected [50]. As Meskal et al. propose, these tests need to be carried out again after successful surgery when patients are off all medications and pain-free. Fear of pain and especially its unpredictability can make patients with TN more hypervigilant and therefore result in more pain [51, 52].

Tolle et al. [53], using psychometric measures in 82 TN patients, and Allsop et al. [54], using one-to-one interviews with 16 TN patients, showed that TN has a considerable impact on quality of life which affects not only the patient but the community where they live.

There are 8 case reports of TN and connective tissue disorders, but the TN is atypical (e.g. bilateral, continuous background pain) and so does not fulfil the criteria for classic TN [55].

Overall the most important comorbidity for TN is MS. Other comorbidities include hypertension and TN patients may be at higher risk of strokes. No psychiatric morbidities other than depression and anxiety have been identified, and these may change after successful surgical management.

The International Headache Society defines persistent idiopathic facial pain as a “persistent facial and/or oral pain, with varying presentations but recurring daily for more than 2 h per day over more than 3 months, in the absence of clinical neurological deficit” (http://​www.​ihs-headache.​org/​ichd-guidelines).

Although previous studies reported a prevalence of persistent idiopathic facial pain of 0.3–0.4 % [3, 56], the unclear case definition of these studies and the lack of widely agreed diagnostic criteria might hamper the reliability of these findings. Persistent idiopathic facial pain, previously defined as atypical facial pain, is a diagnosis of exclusion. Often the onset of pain is preceded by minor operation or injury to the face, maxillae, teeth or gums, but pain persists after healing of the initial noxious event and without any demonstrable local cause. Pain is usually aching, dull, throbbing or pressing and fluctuates in intensity. It is poorly localized; it does not have the characteristics of cranial neuralgia and is not associated with identified lesions affecting the trigeminal system or the facial tissues [57, 58]. Pain may be described as either deep or superficial. With time, it may spread to a wider area of the craniocervical region.

Although a few studies using quantitative sensory testing and neurophysiological examination showed that some patients might have minor somatosensory abnormalities [59], usually persistent idiopathic facial pain is not associated with trigeminal sensory loss or other physical signs, and standard diagnostic tests, such as trigeminal reflex recordings, do not disclose any noteworthy abnormalities of trigeminal afferents [60]. Conversely, functional neuroimaging studies have reported a decrease in striatal dopamine in patients with persistent facial pain [61], thus supporting the recent evidence on the basal ganglia importance in somatosensory system function [62].

Given that neurological examination is normal and no somatosensory afferent pathway damage can be reliably demonstrated, persistent idiopathic facial pain cannot be identified as a neuropathic pain condition [63].

The International Headache Society defines the burning mouth syndrome as an “intraoral burning or dysaesthetic sensation, recurring daily for more than 2 h per day over more than 3 months, without clinically evident causative lesions” (http://​www.​ihs-headache.​org/​ichd-guidelines).

Reported prevalence of burning mouth syndrome in general populations varies from 1 to 15 % [78, 79]. An epidemiological study, investigating 1500 participants, reported a prevalence rate of burning mouth syndrome of 3.7 % (5.5 % in women and 1.6 % in men). The burning mouth syndrome prevalence increases with age, with the highest prevalence (12 %) in women aged 60–69 years [80, 81]. The pain is usually localized in the anterior part of the tongue, the anterior hard palate and the lips. Although burning mouth syndrome is most usually bilateral and symmetrical, some patients report unilateral pain. In most patients pain increases over the day, being most intense in the evening. Most patients also report dry mouth (despite spared saliva secretion) and changes in taste and smell. Burning mouth syndrome is a diagnosis of exclusion. Given that a normal oral mucosa is a prerequisite for the diagnosis, a careful examination of the oral cavity is necessary to confirm the absence of intraoral lesions [82, 83].