Trigeminal Neuralgia Research Articles

Complementary and Integrative Medicine for the Treatment of Trigeminal Neuralgia and Trigeminal Autonomic Cephalalgia.

Trigeminal neuralgia (TN) and trigeminal autonomic cephalalgias (TACs) are both painful diseases which directly impact the branches of the trigeminal nerve, which supply the face. Patients who have experienced adverse effects, have not responded to mainstream treatments, or have a personal preference for nonmedication options, often turn to complementary and integrative medicine (CIM). The aim of this review is to discuss the efficacy and safety of CIM therapies available for the treatment of TN and TACs. Not only are there limited therapeutic options for TN and TAC patients, but also is there a proportion of patients who are intolerant to standard medical treatments. Recent findings have illustrated that 86% of patients with headache disorders utilize CIM modalities in combination with mainstream medical therapy. CIM modalities can be helpful for these diseases and have primarily been studied in combination with standard medical therapy. There is limited evidence for CIM and behavioral therapies in managing these conditions, and more research is needed to confirm which therapies are safe and effective.

Effects of carbamazepine on BDNF expression in trigeminal ganglia and serum in rats with trigeminal neuralgia.

Trigeminal neuralgia (TN) is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy. There are numerous treatments for TN, but currently the main clinical approach is to suppress pain by carbamazepine (CBZ). Brain-derived neurotrophic factor (BDNF) is closely related to chronic pain. This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion (TG) and serum of TN via a chronic constriction injury of the infraorbital nerve (ION-CCI) rat model. The ION-CCI models were established in male Sprague-Dawley rats and were randomly divided into a sham group, a TN group, a TN+low-dose CBZ treatment group (TN+20 mg/kg CBZ group), a TN+medium-dose CBZ treatment group (TN+40 mg/kg CBZ group), and a TN+high-dose CBZ treatment group (TN+80 mg/kg CBZ group). The mechanical pain threshold in each group of rats was measured regularly before and after surgery. The expressions of BDNF and tyrosine kinase receptor B (TrkB) mRNA in TGs of rats in different groups were determined by real-time PCR, and the expression of BDNF protein on neurons in TGs was observed by immunofluorescence. Western Blotting was used to detect the protein expression of BDNF, TrkB, extracellular regulated protein kinases (ERK), and phospho-extracellular regulated protein kinases (p-ERK) in TGs of rats in different groups. The expression of BDNF in the serum of rats in different groups was detected by enzyme-linked immunosorbent assay (ELISA). The results of mechanical pain sensitivity showed that there was no significant difference in the mechanical pain threshold in the right facial sensory area of the experimental rats in each group before surgery (all P>0.05). From the 3rd day after operation, the mechanical pain threshold of rats in the TN group was significantly lower than that in the sham group (all P<0.01), and the mechanical pain threshold of rats in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 CBZ mg/kg group was higher than that in the TN group (all P<0.05). The BDNF and TrkB mRNA and protein expressions in TGs of rats in the TN group were higher than those in the sham group (all P<0.05), and those in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than the TN group (all P<0.05). The p-ERK levels in TG of rats in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were significantly decreased compared with the TN group (all P<0.05). The BDNF and neuron-specific nuclear protein (NeuN) were mainly co-expressed in neuron of TGs in the TN group and they were significantly higher than those in the sham group (all P<0.05). The co-labeled expressions of BDNF and NeuN in TGs of the TN+ 80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than those in the TN group (all P<0.05). The results of ELISA showed that the level of BDNF in the serum of the TN group was significantly higher than that in the sham group (P<0.05). The levels of BDNF in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than those in the TN group (all P<0.05). Spearman correlation analysis showed that the BDNF level in serum was negatively correlated with mechanical pain threshold (r=-0.650, P<0.01). CBZ treatment can inhibit the expression of BDNF and TrkB in the TGs of TN rats, reduce the level of BDNF in serum of TN rats and the phosphorylation of ERK signaling pathway, so as to inhibit TN. The serum level of BDNF can be considered as an indicator for the diagnosis and prognosis of TN.

MiR-21-5p alleviates trigeminal neuralgia in rats through down-regulation of voltage-gated potassium channel Kv1.1.

Trigeminal neuralgia (TN) is a common neuropathic pain. Voltage-gated potassium channel (Kv) has been confirmed to be involved in the occurrence and development of TN, but the specific mechanism is still unclear. MicroRNA may be involved in neuropathic pain by regulating the expression of Kv channels and neuronal excitability in trigeminal ganglion (TG). This study aims to explore the relationship between Kv1.1 and miR-21-5p in TG with a TN model, evaluate whether miR-21-5p has a regulatory effect on Kv1.1, and to provide a new target and experimental basis for the treatment of TN. A total of 48 SD rats were randomly divided into 6 groups: 1) a sham group (n=12), the rats were only sutured at the surgical incision without nerve ligation; 2) a sham+agomir NC group (n=6), the sham rats were microinjected with agomir NC through stereotactic brain injection in the surgical side of TG; 3) a sham+miR-21-5p agomir group (n=6), the sham rats were microinjected with miR-21-5p agomir via stereotactic brain injection in the surgical side of TG; 4) a TN group (n=12), a TN rat model was constructed using the chronic constriction injury of the distal infraorbital nerve (dIoN-CCI) method with chromium intestinal thread; 5) a TN+antagonist NC group (n=6), TN rats were microinjected with antagonist NC through stereotactic brain injection method in the surgical side of TG; 6) a TN+miR-21-5p antagonist group (n=6), TN rats were microinjected with miR-21-5p antagonist through stereotactic brain injection in the surgical side of TG. The change of mechanical pain threshold in rats of each group after surgery was detected. The expressions of Kv1.1 and miR-21-5p in the operative TG of rats were detected by Western blotting and real-time reverse transcription polymerase chain reaction. Dual luciferase reporter genes were used to determine whether there was a target relationship between Kv1.1 and miR-21-5p and whether miR-21-5p directly affected the 3'-UTR terminal of KCNA1. The effect of brain stereotaxic injection was evaluated by immunofluorescence assay, and then the analogue of miR-21-5p (agomir) and agomir NC were injected into the TG of rats in the sham group by brain stereotaxic apparatus to overexpress miR-21-5p. The miR-21-5p inhibitor (antagomir) and antagomir NC were injected into TG of rats in the TN group to inhibit the expression of miR-21-5p. The behavioral changes of rats before and after administration were observed, and the expression changes of miR-21-5p and Kv1.1 in TG of rats after intervention were detected. Compared with the baseline pain threshold, the facial mechanical pain threshold of rats in the TN group was significantly decreased from the 5th to 15th day after the surgery (P<0.05), and the facial mechanical pain threshold of rats in the sham group was stable at the normal level, which proved that the dIoN-CCI model was successfully constructed. Compared with the sham group, the expression of Kv1.1 mRNA and protein in TG of the TN group was down-regulated (both P<0.05), and the expression of miR-21-5p was up-regulated (P<0.05). The results of dual luciferase report showed that the luciferase activity of rno-miR-21-5p mimics and KCNA1 WT transfected with 6 nmol/L or 20 nmol/L were significantly decreased compared with those transfected with mimic NC and wild-type KCNA1 WT, respectively (P<0.001). Compared with low dose rno-miR-21-5p mimics (6 nmol/L) co-transfection group, the relative activity of luciferase in the high dose rno-miR-21-5p mimics (20 nmol/L) cotransfection group was significantly decreased (P<0.001). The results of immunofluorescence showed that drugs were accurately injected into TG through stereotaxic brain. After the expression of miR-21-5p in the TN group, the mechanical pain threshold and the expression of Kv1.1 mRNA and protein in TG were increased. After overexpression of miR-21-5p in the sham group, the mechanical pain threshold and the expression of Kv1.1 mRNA and protein in TG were decreased. Both Kv1.1 and miR-21-5p are involved in TN and miR-21-5p can regulate Kv1.1 expression by binding to the 3'-UTR of KCNA1.

The CSF1-CSF1R pathway in the trigeminal ganglion mediates trigeminal neuralgia via inflammatory responses in mice.

Trigeminal neuralgia (TN) is the most severe type of neuropathic pain. The trigeminal ganglion (TG) is a crucial target for the pathogenesis and treatment of TN. The colony-stimulating factor 1 (CSF1) - colony-stimulating factor 1 receptor (CSF1R) pathway regulates lower limb pain development. However, the effect and mechanism of the CSF1-CSF1R pathway in TG on TN are unclear. Partial transection of the infraorbital nerve (pT-ION) model was used to generate a mouse TN model. Mechanical and cold allodynia were used to measure pain behaviors. Pro-inflammatory factors (IL-6, TNF-a) were used to measure inflammatory responses in TG. PLX3397, an inhibitor of CSF1R, was applied to inhibit the CSF1-CSF1R pathway in TG. This pathway was activated in naïve mice by stereotactic injection of CSF1 into the TG. The TN model activated the CSF1-CSF1R pathway in the TG, leading to exacerbated mechanical and cold allodynia. TN activated inflammatory responses in the TG manifested as a significant increase in IL-6 and TNF-a levels. After using PLX3397 to inhibit CSF1R, CSF1R expression in the TG declined significantly. Inhibiting the CSF1-CSF1R pathway in the TG downregulated the expression of IL-6 and TNF-α to reduce allodynia-related behaviors. Finally, mechanical allodynia behaviors were exacerbated in naïve mice after activating the CSF1-CSF1R pathway in the TG. The CSF1-CSF1R pathway in the TG modulates TN by regulating neuroimmune responses. Our findings provide a theoretical basis for the development of treatments for TN in the TG.

Progress in study on animal models of trigeminal neuralgia.

Trigeminal neuralgia is a manifestation of orofacial neuropathic pain disorder, always deemed to be an insurmountable peak in the field of pain research and treatment. The pain is recurrent, abrupt in onset and termination similar to an electric shock or described as shooting. A poor quality of life has been attributed to trigeminal neuralgia, as the paroxysms of pain may be triggered by innocuous stimuli on the face or inside the oral cavity, such as talking, washing face, chewing and brushing teeth in daily life. The pathogenesis of trigeminal neuralgia has not been fully elucidated, although the microvascular compression in the trigeminal root entry zone is generally considered to be involved in the emergence and progression of the pain disorder. In addition, orofacial neuropathic pain restricted to one or more divisions of the trigeminal nerve might be secondary to peripheral nerve injury. Based on current hypotheses regarding the potential causes, a variety of animal models have been designed to simulate the pathogenesis of trigeminal neuralgia, including models of compression applied to the trigeminal nerve root or trigeminal ganglion, chronic peripheral nerve injury, peripheral inflammatory pain and center-induced pain. However, it has not yet been possible to determine which model can be perfectly employed to explain the mechanisms. The selection of appropriate animal models is of great significance for the study of trigeminal neuralgia. Therefore, it is necessary to discuss the characteristics of the animal models in terms of animal strains, materials, operation methods and behavior observation, in order to gain insight into the research progress in animal models of trigeminal neuralgia. In the future, animal models that closely resemble the features of human trigeminal neuralgia pathogenesis need to be developed, with the aim of making valuable contributions to the relevant basic and translational medical research.

Comparison of initial percutaneous balloon compression versus radiofrequency thermocoagulation followed by percutaneous balloon compression in the treatment of trigeminal neuralgia.

There are a variety of minimally invasive interventional treatments for trigeminal neuralgia, and the efficacy evaluation is different. The preferred treatment scheme is still controversial. This study aims to investigate the differences in treatment effects between patients with primary trigeminal neuralgia (PTN) treated with percutaneous balloon compression (PBC) for the first intervention and patients with pain recurrence after radiofrequency thermocoagulation (RT) who then received PBC for PTN, and to offer clinicians and patients more scientifically grounded and precise treatment alternatives. We retrospectively analyzed 103 patients with PTN admitted to the Department of Pain Management of the Second Affiliated Hospital of Guangxi Medical University from January 2020 to December 2021, including 49 patients who received PBC for the first time (PBC group) and 54 patients who received PBC for pain recurrence after RT (RT+PBC group). General information, preoperative pain score, intraoperative oval foramen morphology, oval foramen area, balloon volume, duration of compression, and postoperative pain scores and pain recurrence at each time point on day 1 (T1), day 7 (T2), day 14 (T3), 1 month (T4), 3 months (T5), and 1 year (T6) were collected and recorded for both groups. The differences in treatment effect, complications and recurrence between the 2 groups were compared, and the related influencing factors were analyzed. The differences of general information, preoperative pain scores, foramen ovale morphology, foramen ovale area, T1 to T3 pain scores between the 2 groups were not statistically different (all P>0.05). The balloon filling volume in the PBC group was smaller than that in the RT+PBC group, the pain scores at T4 to T6 and pain recurrence were better than those in the RT+PBC group (all P<0.05). Pain recurrence was positively correlated with pain scores of T2 to T6 (r=0.306, 0.482, 0.831, 0.876, 0.887, respectively; all P<0.01). The choice of PBC for the first intervention in PTN patients is superior to the choice of PBC after pain recurrence after RT treatment in terms of treatment outcome and pain recurrence.

Activation of A1 reactive astrocytes in the medullary dorsal horn of rats participates in the chronification of trigeminal neuralgia.

The activation of astrocytes is an important process in the formation of chronic pain. This study aims to observe the activation of A1 reactive astrocytes in the medullary dorsal horn in the rat model of trigeminal neuralgia, and to explore the mechanism of central sensitization caused by A1 reactive astrocyte. The adult male rats were randomly divided into a sham group and a chronic constriction injury of infraorbital nerve (ION-CCI) group. The facial mechanical pain threshold and thermal withdrawal latency were measured before the operation and on the 1st, 3rd, 7th, 10th, and 14th day after the operation. After pain behavior observation, the expression of glial fibrillary acidic protein (GFAP) in the medullary dorsal horn was observed by immunohistochemistry and immunofluorescence colocalization of GFAP, complement 3 (C3)/S100A10, and 4', 6-diamidino-2-phenylindole (DAPI) was analyzed. Primary astrocytes were cultured and randomly divided into a naive group and a DHK group. The DHK group was treated with 1 mmol/L of astrocyte activation inhibitor dihydrokainic acid (DHK). Fura-2/AM was used to stain the astrocytes and the calcium wave of the 2 groups under the stimulation of high potassium was recorded and compared. The expression of C3 was detected by Western blotting. The facial mechanical pain threshold and thermal withdrawal latency of the ION-CCI group were significantly lower than those of the sham group (both P<0.05). There were a large number of GFAP positive astrocytes in the medullary dorsal horn of the ION-CCI group. The fluorescence intensity of GFAP in the ION-CCI group was higher than that in the sham group (P<0.05). GFAP and C3/S100A10 were co-expressed in astrocytes. Compared with the sham group, the fluorescence intensity of C3 and the protein expression of C3 in the ION-CCI group were increased (both P<0.05). The expression of C3 in ION-CCI group was significantly increased (P<0.05). Compared with the naive group, the C3 protein expression was significantly decreased in the DHK group (P<0.05). The intensity of calcium fluorescence was increased after high potassium stimulation in both groups. Furthermore, the peak and increase amplitude of calcium fluorescence in the naive group were much higher than those in the DHK group (both P<0.05). A1 reactive astrocytes in the medullary dorsal horn of trigeminal neuralgia model rats are increased significantly, which may participate in central sensitization of trigeminal neuralgia by impacting astrocyte calcium wave.

A Pilot Study of Hypofractionated Radiosurgery for Trigeminal Neuralgia.

The primary late toxicity of radiosurgery treatment for trigeminal neuralgia (TN) is facial numbness due to trigeminal nerve dysfunction. Although most patients prefer loss of facial sensation to TN, severe loss of facial sensation can be debilitating. In order to try to obtain high pain control rates while minimizing the risk of late facial numbness, we elected to treat patients on the distal trigeminal nerve with a three-fraction regimen over consecutive days instead of one fraction. Our goal was to relieve the pain while also allowing the trigeminal nerve time to repair radiation damage between treatments in an attempt to minimize the risk of permanent facial numbness. Patients in a pilot study, approved by an Institutional Review Board (IRB), received a treatment regimen of 99 Gy, administered in three consecutive daily fractions of 33 Gy each, with the dosage targeted to the 80% line. This dose was selected to approximate a biologically equivalent dose of 80 Gy maximal dose to the trigeminal nerve. Forty-eight patients were treated with CyberKnife Radiosurgery (CKRS; 99 Gy/3 fractions) for TN from 2016 to 2022, with at least one year of follow-up. The Barrow Neurological Institute (BNI) scale was used to assess facial pain, and Kaplan-Meier analysis was used to assess adequate pain relief. Thirty-eight (84%) patients experienced adequate pain relief, defined as a BNI score of I-IIIb, after a median of 1.5 months following CKRS. Treatment failure (BNI=IV-V) occurred in 12 (25%) patients after a median of 6 months following initial pain relief. The actuarial probability of pain relief at 6, 12, and 24 months post-CKRS were 87.4%, 83.7%, and 83.7%, respectively. Facial numbness was experienced in 24 (50%) cases after a median of 10 months following CKRS. Typical facial pain (p=0.034) and vascular compression (p=0.039) were the only predictors of better treatment outcomes using univariate Cox survival analysis, and vascular compression (p= 0.037) was the only predictor in multivariate Cox survival analysis. Hypofractionated treatment to the distal trigeminal nerve segment does not appear to offer an advantage in treating TN, due to similar rates of pain relief but with an unacceptably high rate of late facial numbness.

Bipolar, high-voltage, long-duration pulsed radiofrequency ablation of the Gasserian ganglion for the treatment of trigeminal neuralgia in a patient with a cardiac implantable electronic device: illustrative case.

One of the common methods of treating trigeminal neuralgia (TN) nowadays is radiofrequency therapy. However, it has serious limitations in patients with a cardiac pacemaker because of electromagnetic interference. Therefore, it is crucial to select optimal radiofrequency ablation parameters to make this procedure safe with favorable outcomes for such patients. In this study, the authors present a case of a 70-year-old man with a history of cardiac pacemaker dependency and previous microvascular decompression with complaints of severe, constant facial pain. After reprogramming the cardiac implantable electronic device (CIED), the authors performed bipolar, high-voltage, long-duration pulsed radiofrequency therapy (PRFT) of the Gasserian ganglion under electrocardiography and pulse rate control in the pre-, intra-, and postoperative periods. There were no cardiovascular or neurological complications after PRFT. The patient reported relief of pain after the procedure, and at the 9-month follow-up, he was pain-free. This clinical case demonstrates that the use of bipolar, high-voltage PRFT for TN treatment in patients with a CIED can be safe and effective, provided that the rules and pacemaker instructions are followed. It is necessary to use ablative treatment with caution and to guide the patient in collaboration with a cardiac surgeon and an anesthesiologist resuscitator.

A Randomized Controlled Trial Comparing the Effect of Two-Time Durations of Balloon Compression During Percutaneous Balloon Compression in Resistant Trigeminal Neuralgia

BACKGROUND: Percutaneous balloon compression of the trigeminal nerve’s gasserian ganglion for the treatment of trigeminal neuralgia is an interventional pain procedure with results comparable to microvascular decompression surgery. The procedure is safe in experienced hands and has less morbidity associated with it. However, there is a lack of clear-cut guidelines about the details of the technique like balloon shape, inflation pressure, and duration of inflation. So, keeping the inflation pressure and shape of the balloon constant, we studied the effect of the duration of inflation of the balloon and its effect on pain relief in refractory trigeminal neuralgia cases. OBJECTIVES: To study the outcome with 2 different durations of balloon inflation times in terms of pain relief and complications after percutaneous balloon compression. STUDY DESIGN: Prospective parallel design randomized, controlled trial. SETTING: The study was conducted in a tertiary care hospital in North Eastern India after obtaining approval from the Institutes’ ethics committee (Dean/2018/EC/449). The study was also registered with the Clinical Trials Registry of India (CTRI no. CTRI/2019/03/018166). All patients referred to a pain clinic for unilateral facial pain were screened for the study over 2 years from April 2019 to March 2021. METHODS: Forty patients who met the diagnosis of trigeminal neuralgia and who did not respond satisfactorily to medications were included in the study. They underwent routine blood investigations and a magnetic resonance image of the brain to rule out any medical or surgical conditions. Percutaneous balloon compression was conducted under C-arm guidance using a 12 gauge cannula and a 4 Fr Fogarty balloon was used for compressing the gasserian rootlets. RESULTS: Patients who underwent 90 seconds as well as 120 seconds showed good pain relief. The 2 groups did not show any significant difference in pain relief based on the duration of compression. Visual analog scale scores were reduced from 7-8 to 0-3. Masseter muscle weakness was present in 47.5% of patients post-procedure and recovered in all except one patient. LIMITATIONS: We have followed up with our patients for a short period of 6 months only. We could not measure the intra-luminal compression pressure of the balloon. CONCLUSION: There is no difference in the pain relief obtained by the 2 different durations of compressions. A longer duration of compression, however, has more incidence of side effects. KEY WORDS: Idiopathic trigeminal neuralgia, percutaneous balloon compression, time duration, shape of balloon, masseter muscle weakness, facial numbness, corneal dysesthesia

Endoscopic Versus Microscopic Microvascular Decompression for Trigeminal Neuralgia: A Prospective Controlled Study

BACKGROUND: Several studies have suggested favorable results with endoscope-assisted microvascular decompression (EA-MVD) for treating patients with trigeminal neuralgia (TN); however, supporting evidence is limited. OBJECTIVES: This study aimed to compare the efficacy and safety of EA-MVD with microscopic microvascular decompression (M-MVD). STUDY DESIGN: Prospective controlled study. SETTING: We performed a prospective controlled clinical study that included 52 patients with TN (36, [69.2%] women; 16, [30.8%] men), from June 2021 through January 2022. METHODS: Patients were assigned to receive either EA-MVD (n = 23) or M-MVD (n = 29). The primary outcome was pain intensity relief, measured using the Visual Analog Scale (VAS) and the Barrow Neurological Institute grading scale. The secondary outcomes were the detection of multiple offending vessels, endoscopic use, operation time, hospital stay length, and complications. All patients were followed-up for &gt;= 12 months. RESULTS: At 12 months, both treatment groups showed similar improvements in pain intensity (P = 0.099). The mean VAS score was 3.5 ± 1.6 and 2.9 ± 1.7 in the EA-MVD and M-MVD groups, respectively. Overall, most patients in both groups reached a pain-free status or had nearly pain-free relief (EA-MVD: 21/23, 91.3%; M-MVD: 27/29, 93.1%). The incidence of multiple offending vessels was higher in the EA-MVD group than in the M-MVD group (52.2% vs 17.2%, P = 0.038). The mean operating time in the EA-MVD group (158 ± 27 minutes) was longer and the hospital stay (6 ± 1 days) was shorter than those of the M-MVD group (144 ± 25 minutes and 8 ± 4 days). No mortality or endoscope-related serious adverse events were noted, with the exception of an intracranial infection case in the M-MVD group. LIMITATIONS: The mean follow-up time was relatively short and a single-center study and a small patient population, which might bring some clinical bias. CONCLUSIONS: M-MVD and EA-MVD achieved similar analgesic effects for TN; however, EA-MVD allowed observation of more probable offending vessels with good flexible operative visualization. KEY WORDS: Trigeminal neuralgia, microvascular decompression, endoscope-assisted microvascular decompression, endoscopic surgery, suprameatal tubercle, visual analog scale, minimally invasive surgery, neuropathic pain

Mapping trends in hemifacial spasm research: bibliometric and visualization-based analyses of the Web of Science Core Collection.

Hemifacial spasm (HFS) is a common cranial nerve disease. In HFS research, we conducted a bibliometric analysis to examine the development and research trends. A retrieval of HFS studies published between 2011 and 2022 was performed from the Web of Science Core Collection in September 2022. Two scientometric tools were used to perform bibliometric and visualization-based analyses: VOSviewer and CiteSpace. Bibliometric analysis of 1461 studies published between 2011 and 2022 was carried out using data from 444 journals, 6021 authors, 1732 institutions, and 76 countries/regions. China, the USA, Japan, and South Korea were four key contributors to this study. Shanghai Jiaotong University was the major institution with the larger number of publications. Li Shiting was the most prolific author. Jannetta PJ was the most co-cited author. World Neurosurgery was the top prolific journal. Journal of Neurosurgery was the top co-cited journal. The top five keywords were hemifacial spasm, microvascular decompression, trigeminal neuralgia, surgery, and neurovascular compression. This study examines the research trends in global scientific research on HFS over the last decade. Researchers interested in learning more about current trends and novel research frontiers in this area can benefit from the study.

Analysis of the Therapeutic Efficacy of Percutaneous Balloon Double Compression for the Treatment of Recurrent Trigeminal Neuralgia

BACKGROUND: A more secure and efficacious therapy than has been developed so far is imperative for patients suffering from recurrent trigeminal neuralgia (TN). Despite numerous reports on the use of enhanced percutaneous balloon compression (PBC) techniques, such as altering compression duration and balloon pressure, none have yielded satisfactory outcomes. With these issues in mind, we have employed the PBC double-compression technique for the first time. This technique involves initially inflating a balloon to expand the adhesive tissue in Meckel’s lumen, followed by emptying of the contrast medium and subsequent slight catheter adjustment for further compression. The total duration of compression remains unchanged and may even be shortened. OBJECTIVES: The objective of this study was to assess the clinical effectiveness of the PBC double-compression technique in patients with recurrent TN and to analyze the technique’s efficacy, subsequent duration of patients’ facial numbness, and other complications. STUDY DESIGN: Retrospective study. SETTING: A single-center study. METHODS: Retrospective analysis was conducted on clinical data from 125 patients with postoperative recurrent TN who underwent double compression of the PBC and 65 patients who underwent single compression of the PBC between August 2017 and April 2022. The Barrow Neurological Institute Pain Intensity (BNI-P) score was utilized to quantify the severity of pain, while the Barrow Neurological Institute Facial Numbness (BNI-N) score was employed to separately evaluate the extent of postoperative pain relief and facial numbness. RESULTS: The BNI-P and BNI-N scores before and after PBC treatment are presented herein. At T0, there was no significant difference in the BNI-P scores between the single-compression group and the double-compression group; however, at T1-T4, the BNI-P scores of the double-compression group were lower than those of the single-compression group (P &lt; 0.05). There was no significant difference in BNI-P scores between the 2 groups at T5. At T1-T4, the BNI-N score of the double-compression group was significantly lower than that of the single-compression group (P &lt; 0.05). However, there was no significant difference in BNI-N score between the double and single compression groups at T5. In the single-compression group, one patient (1.5%) experienced insignificant pain relief on postoperative day one, while 2 patients (3.1%) suffered from pain recurrence during the 1-4-year follow-up period. Similarly, in the double-compression group, one patient (0.8%) had inadequate pain relief on postoperative day one, and 3 patients (2.4%) experienced pain recurrence during the same follow-up period. The remaining patients did not require further surgical intervention but continued to rely on regular oral analgesia. In the single-compression group, masticatory muscle weakness was observed in 50 cases (76.9%), while in the double-compression group, it was observed in 92 cases (73.6%). Perioral herpes affected 4 patients (7.1%) and 6 patients (4.8%) in the single- and double-compression groups, respectively. Facial hematoma occurred in 7 cases (10.8%) and 13 cases (10.4%) of the single- and double-compression groups, respectively; each group included one patient suffered who from diplopia. Notably, none of the patients in this study reported any instances of corneal anesthesia, anesthesia pain, aseptic meningitis, cerebrospinal fluid leakage, subarachnoid hemorrhage, carotid-cavernous fistula, or mortality. LIMITATIONS: This was a single-center retrospective study with a small sample size and relatively short follow-up time. Therefore, further evaluation of the long-term efficacy of PBC for postoperative recurrent TN is needed from multiple centers with larger sample sizes and longer follow-up periods. CONCLUSIONS: The double PBC method boasts a high cure rate, a low recurrence rate, and minimal complications, rendering the option appropriate for patients with recurrent TN and thus deserving of clinical promotion. KEY WORDS: Percutaneous balloon compression, recurrent trigeminal neuralgia, double-compression method

Corticotropin-releasing hormone neurons control trigeminal neuralgia-induced anxiodepression via a hippocampus-to-prefrontal circuit.

Anxiety and depression are frequently observed in patients suffering from trigeminal neuralgia (TN), but neural circuits and mechanisms underlying this association are poorly understood. Here, we identified a dedicated neural circuit from the ventral hippocampus (vHPC) to the medial prefrontal cortex (mPFC) that mediates TN-related anxiodepression. We found that TN caused an increase in excitatory synaptic transmission from vHPCCaMK2A neurons to mPFC inhibitory neurons marked by the expression of corticotropin-releasing hormone (CRH). Activation of CRH+ neurons subsequently led to feed-forward inhibition of layer V pyramidal neurons in the mPFC via activation of the CRH receptor 1 (CRHR1). Inhibition of the vHPCCaMK2A-mPFCCRH circuit ameliorated TN-induced anxiodepression, whereas activating this pathway sufficiently produced anxiodepressive-like behaviors. Thus, our studies identified a neural pathway driving pain-related anxiodepression and a molecular target for treating pain-related psychiatric disorders.

Glia-derived adenosine in the ventral hippocampus drives pain-related anxiodepression in a mouse model resembling trigeminal neuralgia

Glial activation and dysregulation of adenosine triphosphate (ATP)/adenosine are involved in the neuropathology of several neuropsychiatric illnesses. The ventral hippocampus (vHPC) has attracted considerable attention in relation to its role in emotional regulation. However, it is not yet clear how vHPC glia and their derived adenosine regulate the anxiodepressive-like consequences of chronic pain. Here, we report that chronic cheek pain elevates vHPC extracellular ATP/adenosine in a mouse model resembling trigeminal neuralgia (rTN), which mediates pain-related anxiodepression, through a mechanism that involves synergistic effects of astrocytes and microglia. We found that rTN resulted in robust activation of astrocytes and microglia in the CA1 area of the vHPC (vCA1). Genetic or pharmacological inhibition of astrocytes and connexin 43, a hemichannel mainly distributed in astrocytes, completely attenuated rTN-induced extracellular ATP/adenosine elevation and anxiodepressive-like behaviors. Moreover, inhibiting microglia and CD39, an enzyme primarily expressed in microglia that degrades ATP into adenosine, significantly suppressed the increase in extracellular adenosine and anxiodepressive-like behaviors. Blockade of the adenosine A2A receptor (A2AR) alleviated rTN-induced anxiodepressive-like behaviors. Furthermore, interleukin (IL)-17A, a pro-inflammatory cytokine probably released by activated microglia, markedly increased intracellular calcium in vCA1 astrocytes and triggered ATP/adenosine release. The astrocytic metabolic inhibitor fluorocitrate and the CD39 inhibitor ARL 67156, attenuated IL-17A-induced increases in extracellular ATP and adenosine, respectively. In addition, astrocytes, microglia, CD39, and A2AR inhibitors all reversed rTN-induced hyperexcitability of pyramidal neurons in the vCA1. Taken together, these findings suggest that activation of astrocytes and microglia in the vCA1 increases extracellular adenosine, which leads to pain-related anxiodepression via A2AR activation. Approaches targeting astrocytes, microglia, and adenosine signaling may serve as novel therapies for pain-related anxiety and depression.

Repeat Gamma Knife radiosurgery for recurrent trigeminal neuralgia in patients with multiple sclerosis: a single-center retrospective study.

Gamma Knife radiosurgery (GKRS) has emerged as an effective treatment option for trigeminal neuralgia (TN) in patients with multiple sclerosis (MS). To date, the outcomes of repeat GKRS for patients with TN and MS with recurrent pain have been investigated in a few patients. This study aims to report the outcomes and predictive factors of pain reduction for MS patients undergoing repeat GKRS for recurrent TN. Eighteen patients with MS underwent repeat GKRS for recurrent TN. A retrospective chart review and telephone interviews were conducted to determine background medical history, dosimetric data, and outcomes of the procedure. Facial pain and sensory function were evaluated using the Barrow Neurological Institute (BNI) scales. Fifteen patients achieved a BNI pain score of IIIa or better, indicating pain reduction, within a median period of 21 days after repeat GKRS. The maximum dose for repeat GKRS ranged from 70 to 85 Gy. Pain recurred in 5 patients after a median period of 12 months after GKRS. Percentages of patients with pain reduction at 1, 2, 3, 5, and 7 years were 60%, 60%, 50%, 50%, and 50%, respectively. Older age at repeat GKRS predicted sustained pain reduction (P = 0.01). Seven patients developed facial sensory disturbances, which were bothersome in two patients. Repeat GKRS may be used as an effective treatment modality for prolonging the duration of pain reduction time in patients with MS and TN. After repeat GKRS, facial sensory disturbances are common; however, they are often not bothersome.

Daily olive oil intake is feasible to reduce trigeminal neuralgia facial pain: A pilot study

Extra virgin olive oil (EVOO) is thought to contribute to neuroprotection and, thus, may influence pain symptoms experienced by adults with demyelination-related trigeminal neuralgia (TN). This study aimed to determine the feasibility of daily intake of EVOO and its potential to alleviate facial pain of TN. Adults, self-reporting as female and affected by TN, were enrolled in a 16-week nonblinded, parallel study. After a 4-week baseline, participants were randomized to 60 mL/day EVOO or control (usual diet and no supplemental EVOO) for 12 weeks. Participants completed a daily questionnaire on pain intensity and compliance, the Penn Facial Pain Scale weekly, the 36-Item Short Form Survey monthly, and dietary assessment during baseline and intervention. Participants (n = 52; 53.3 ± 12.9 years) were recruited nationally; 42 completed the study. The EVOO group, with 90% intake compliance, showed significant decreases in the Penn Facial Pain Scale items of interference with general function, interference with orofacial function, and severity of pain from baseline, whereas the control group showed no improvements. EVOO benefit, compared with control, trended for the interference with orofacial function (P = .05). The 36-Item Short Form Survey items of role limitations resulting from emotional problems and role limitations from physical health favored EVOO. The EVOO group significantly improved their Healthy Eating Index 2015 component scores of fatty acids (primarily from increased oleic acid), sodium, and refined grains. EVOO intake of 60 mL/day was feasible for participants experiencing TN and may mitigate pain and improve quality of life. This trial was registered at clinicaltrials.gov (NCT05032573).

Association Between Foramen Rotundum and Trigeminal Neuralgia in the Saudi Population: A Radiological Study

Association Between Foramen Rotundum and Trigeminal Neuralgia in the Saudi Population: A Radiological Study

The long-term outcome of CT-guided radiofrequency ablation of the peripheral branches of the trigeminal nerve in trigeminal neuralgia.

Radiofrequency thermocoagulation (RFTC) of the peripheral branches of the trigeminal nerve has been used for trigeminal neuralgia. However, the long-term outcomes of radiofrequency thermocoagulation have not been established. To evaluate the long-term efficacy of RFTC of peripheral branches in patients with refractory trigeminal neuralgia. A retrospective cohort study was conducted in a comprehensive medical center in China. Patients who underwent radiofrequency thermocoagulation of peripheral branches for refractory trigeminal neuralgia from May 2014 to March 2021 were included for analysis. A total of 84 patients with refractory trigeminal neuralgia underwent 105 procedures. BNI I-II which represents treatment success was achieved in 76/84 (90%) patients and 93/105 (89%) procedures. During follow-up, BNI I and II were maintained in 64/76 (84%), 40/73 (55%), 20/67 (30%), 17/65 (26%), 12/61 (20%), and 8/58 (14%) of patients at 1, 2, 3, 4, 5, and 6 years, after the first procedure, respectively. For all the 105 procedures, BNI I and II were maintained in 68/93 (73%), 41/89(46%), 22/82(27%), 15/79 (19%), 8/74 (11%), and 3/72 (4%) at 1, 2, 3, 4, 5, and 6 years, respectively. There is no significant difference between the first and repeat thermocoagulation in terms of immediate (90% vs. 81%, P=0.140) and long-term efficacies (24 months vs.18 months, P=0.266). Radiofrequency thermocoagulation resulted in better long-term outcomes in patients with typical purely paroxysmal pain (24 months vs. 11 months, P=0.033). Radiofrequency ablation of the peripheral branches of the trigeminal nerve might be a safe and effective method in the treatment of refractory trigeminal neuralgia.

Comparative safety and efficacy of percutaneous radiofrequency thermocoagulation and percutaneous balloon compression in CT-guided and local anesthesia for recurrent trigeminal neuralgia.

There are several ways to treat trigeminal neuralgia (TN); however, TN may recur after treatment. Although microvascular decompression (MVD) is considered an effective treatment for trigeminal neuralgia, patients with recurrence may not be willing to undergo craniotomy. This study compared the safety and efficacy of percutaneous radiofrequency thermocoagulation and percutaneous balloon compression for treating recurrent trigeminal neuralgia. This was a prospective non-randomized controlled study. A total of 52 with recurrent TN were scheduled to undergo surgery in our Hospital from January-June 2021. The patients were classified into percutaneous radiofrequency thermocoagulation (PRT) and percutaneous balloon compression (PBC) groups based on the treatment. All surgeries were performed under computed tomography guidance and local anesthesia. Post-operative complications were also observed. Pain was assessed using the visual analog scale (VAS) and Barrow Neurological Institute (BNI) scale. Efficacy indices were evaluated at 3, 6, 12, and 18 months after surgery. During follow-up, the efficacy rates of the two methods within 18 months were 76.0 and 88.9%, respectively. All patients had hypoesthesia on the affected side, and no severe complications. Notably, 5 patients (20%) in the PRT group with multiple-branch pain, including the first branch of the trigeminal nerve (V1) pain in the PRT group, received radiofrequency therapy for the supraorbital notch (foramen) after puncture of the foramen ovale. However, multiple pain episodes resolved with only one operation in the PBC group. CT-guided percutaneous radiofrequency thermocoagulation and percutaneous balloon compression under local anesthesia may be good options for treating recurrent trigeminal neuralgia. Percutaneous balloon compression may be recommended when multiple branches are involved, particularly in cases of V1 neuralgia.