Trigeminal neuralgia (TN), including primary TN and secondary TN, is the most common neuralgia in brain diseases or neuropathic pain [1]. It is characterized by recurrent electric shock, transient and severe pain in the area of facial trigeminal nerve distribution [2]. Globally, 15 out of 100,000 people suffer from trigeminal neuralgia [3]. In addition, it was reported that the prevalence rate of females was higher than that of males, the incidence rate of the right side was higher than that of the left side, and it was more common in middle-aged and older people [4]. Trigeminal neuralgia seriously affects people’s daily work and life and will have a specific impact on mental health [5].

Up to now, the main treatments for trigeminal neuralgia are drug therapy, including carbamazepine (CBZ) and oxcarbazepine (OXC) [6], gamma knife radiosurgery (GKRS) [7], percutaneous balloon compression (PBC) [8], glycerol rhizotomy (GR) [9], radiofrequency thermocoagulation (RFTC) [10], microvascular decompression (MVD) [11] and so on. Based on the vascular compression theory [12]. MVD is the first choice for the treatment of primary TN to provide the most prolonged duration of pain freedom [13]. However, in MVD, we found that this operation is only suitable for some patients but not for other patients [14]. Therefore, the microscopic endoscopic-assisted (MEA) technique was used when the conflict was not identified under microscopic view or was not certainly resolved. In patients with ineffective MVD, trigeminal nerve combing and partial sensory root section (PSRS) are used for treatment [15, 16]. Therefore, it is of great value to objectively judge the function and abnormality of the trigeminal pain conduction pathway in guiding the operation process. The purpose of this study was to investigate the clinical diagnostic value of pain evoked potential by electrical stimulation and nociceptive blink reflex (NBR) in TN.

TN is a kind of recurrent neuropathic pain characterized by the sudden appearance, short duration, and acupuncture-like pain on one side of the face. It often involves one or more trigeminal nerves [18]. A previous epidemiological survey showed that the onset age of TN was mainly 37–67 years old, the ratio of male to female was about 1 : 3 [19]. At present, the pathogenesis of TN has not been clear, mainly including “peripheral pathogenic theory” and “central pathogenic theory”. The most popular peripheral pathogenic theory is vascular compression theory, which holds that demyelination of trigeminal nerve is the key to TN [20, 21]. According to the theory of central pathogenesis, the key to TN is the impairment of the nerve fiber network and functional connection in the spinal trigeminal nucleus, brain stem, thalamus and cerebral cortex [22, 23, 24].

Physiological examination of pain evoked potential by electrical stimulation is a new, fast and convenient examination to judge the nerve function of patients with pain. It can stimulate the skin of the trigeminal nerve distribution area through a specially designed concentric electrode, which can excite the pain nerve fibers of the corresponding area alone to objectively judge the function and abnormality of the trigeminal pain conduction pathway [25]. Blink reflex (BR) is a critical electrophysiological method to detect trigeminal and facial nerve injury [26]. In addition, BR, including early response R${}_1$ on the stimulation side and late response R${}_2$ and R${}_2$ on both sides, is a critical electrophysiological index reflecting brainstem function, which is widely used in the clinical evaluation of brainstem function [27].

We found that the latency and amplitude of V${}_1$, V${}_2$, V${}_3$ and R${}_2$ of the affected side in the observation group were not statistically significant compared to the opposite side. In addition, the latency of V${}_1$, V${}_2$, V${}_3$ and R${}_2$ of the affected side in the observation group was not statistically significant compared to that of the same side in the control group. Still, the amplitude was statistically significant compared to that of the same side in the control group. Our results suggested that the amplitudes of pain evoked potential and blink reflex were more clinically significant than the latencies. This is consistent with the previous research of some scholars. Papagianni et al. [28] found that the amplitude of pain evoked potential can reflect the function of pain nerve fibers. Hansen et al. [29] have also confirmed this point. It has been found that the R${}_2$ amplitude of BR is significantly reduced when the brainstem level lesions cause hypoesthesia [30]. In addition, previous studies have shown that the R${}_2$ response of blink reflex is mostly central neuropathy [31, 32]. This study also showed that the R${}_2$ amplitude of patients with TN had significant changes in blink reflex examination. Whether a pain evoked potential or blink reflex, the latency represents demyelinating lesion, while the amplitude represents axonal lesion. Therefore, we speculated that the pathogenesis of TN could not be fully explained by the theory of vascular compression, which needed to integrate “peripheral pathogenic theory” and “central pathogenic theory”.

ROC curve analysis showed that the AUC, sensitivity and specificity of the ROC curve of the joint diagnosis of the latency and amplitude of V${}_1$, V${}_2$, V${}_3$ and R${}_2$ were significantly higher than those of the single diagnosis. Therefore, combined diagnosis is more clinically useful for the diagnosis of TN. At the same time, we also found that the latency and amplitude of V${}_1$ were highly sensitive in the diagnosis of TN, while the amplitude and latency of V${}_2$ and R${}_2$ were highly specific. We considered that the difference was related to the pathway of the trigeminal nerve and the site of injury. This needs to be further studied with a large number of samples in the future.

In conclusion, our results suggested that TN can be effectively diagnosed by combining pain evoked potential by electrical stimulation and BR. The pathogenesis of trigeminal neuralgia should be combined with peripheral pathogenicity and the theory of central pathogenicity.

TN, Trigeminal neuralgia; OXC, oxcarbazepine; GKRS, gamma knife radiosurgery; PBC, percutaneous balloon compression; RFTC, radiofrequency thermocoagulation; MVD, microvascular decompression; PSRS, partial sensory root section; BR, blink reflex; AUC, area under curve; NBR, nociceptive blink reflex.

JR and GL conceived and designed the experiments; YH, YL, XZ performed the experiments; JR, YH, YL and XZ carried out clinical studies; JR analyzed the data; JR contributed definition of intellectual content and literature research; YL, XZ contributed data acquisition; JR and YH wrote the paper. GL reviewed the paper.

The ethics committee approved this work of the Sanbo Brain Hospital, Capital Medical University. In addition, written informed consent was obtained from all individual participants included in the research.

Not applicable.

This work was supported by the Beijing Municipal Science & Technology Commission’s grants/Award Number: Z141107002514152.

The authors declare no conflict of interest.