A Case of Trigeminal Neuralgia in an Adult Patient With Lambdoid Synostosis.

Trigeminal neuralgia (TN) is characterized by sudden, brief intense pain in the distribution of the unilateral trigeminal nerve (TGN). Neurovascular compression (NVC) of the TGN is the most common cause of TN. Recent studies have suggested that a structural anomaly of the posterior cranial fossa might be involved in the development of TN, and several studies have documented the association between NVC-related TN and congenital posterior cranial deformities in adults. We present the case of a 56-year-old woman with NVC-related TN and unilateral lambdoid synostosis (ULS), along with a literature review, to investigate the relationship between TN and structural anomalies of the posterior fossa. This is the first report of TN in an adult with ULS. Mild and asymptomatic cases of lambdoid synostosis might have a higher incidence of NVC-related TN in association with posterior cranial fossa deformities.

Hippocampus diffusivity abnormalities in classical trigeminal neuralgia.

Introduction: Patients with chronic pain frequently report cognitive symptoms that affect memory and attention, which are functions attributed to the hippocampus. Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by paroxysmal attacks of unilateral orofacial pain. Given the stereotypical nature of TN pain and lack of negative symptoms including sensory loss, TN provides a unique model to investigate the hippocampal implications of chronic pain. Recent evidence demonstrated that TN is associated with macrostructural hippocampal abnormalities indicated by reduced subfield volumes; however, there is a paucity in our understanding of hippocampal microstructural abnormalities associated with TN. Objectives: To explore diffusivity metrics within the hippocampus, along with its functional and structural subfields, in patients with TN. Methods: To examine hippocampal microstructure, we utilized diffusion tensor imaging in 31 patients with TN and 21 controls. T1-weighted magnetic resonance images were segmented into hippocampal subfields and registered into diffusion-weighted imaging space. Fractional anisotropy (FA) and mean diffusivity were extracted for hippocampal subfields and longitudinal axis segmentations. Results: Patients with TN demonstrated reduced FA in bilateral whole hippocampi and hippocampal body and contralateral subregions CA2/3 and CA4, indicating microstructural hippocampal abnormalities. Notably, patients with TN showed significant correlation between age and hippocampal FA, while controls did not exhibit this correlation. These effects were driven chiefly by female patients with TN. Conclusion: This study demonstrates that TN is associated with microstructural hippocampal abnormalities, which may precede and potentially be temporally linked to volumetric hippocampal alterations demonstrated previously. These findings provide further evidence for the role of the hippocampus in chronic pain and suggest the potential for targeted interventions to mitigate cognitive symptoms in patients with chronic pain.

A novel indicator to predict the outcome of percutaneous stereotactic radiofrequency rhizotomy for trigeminal neuralgia patients: diffusivity metrics of MR-DTI.

Magnetic resonance-diffusion tensor imaging (MR-DTI) has been used in the microvascular decompression and gamma knife radiosurgery in trigeminal neuralgia (TN) patients; however, use of percutaneous stereotactic radiofrequency rhizotomy (PSR) to target an abnormal trigeminal ganglion (ab-TG) is unreported. Fractional anisotropy (FA), mean and radial diffusivity (MD and RD, respectively), and axial diffusivity (AD) of the trigeminal nerve (CNV) were measured in 20 TN patients and 40 healthy control participants immediately post PSR, at 6-months, and at 1 year. Longitudinal alteration of the diffusivity metrics and any correlation with treatment effects, or prognoses, were analyzed. In the TN group, either low FA (value < 0.30) or a decreased range compared to the adjacent FA (dFA) > 17% defined an ab-TG. Two-to-three days post PSR, all 15 patients reported decreased pain scores with increased FA at the ab-TG (P < 0.001), but decreased MD and RD (P < 0.01 each). Treatment remained effective in 10 of 14 patients (71.4%) and 8 of 12 patients (66.7%) at the 6-month and 1-year follow-ups, respectively. In patients with ab-TGs, there was a significant difference in treatment outcomes between patients with low FA values (9 of 10; 90%) and patients with dFA (2 of 5; 40%) (P < 0.05). MR-DTI with diffusivity metrics correlated microstructural CNV abnormalities with PSR outcomes. Of all the diffusivity metrics, FA could be considered a novel objective quantitative indicator of treatment effects and a potential indicator of PSR effectiveness in TN patients.

Neurorehabilitation Strategies: Assessing the Impact on Postoperative Psychological State, Pain, and Complications in Trigeminal Neuralgia.

BACKGROUND: Trigeminal neuralgia is a difficult clinical situation marked by excruciating pain that requires efficient postoperative measures. In patients with trigeminal neuralgia, this study sought to investigate the effects of ongoing rehabilitation intervention on postoperative outcomes, including psychological state, pain, and complications. The aim was to provide new perspectives and treatment strategies for the management of this crippling illness. NEW METHOD: Between January 2021 and December 2022, 120 patients receiving treatment for trigeminal neuralgia were randomized to either the observation or control groups. The observation group received a continuous and comprehensive rehabilitation intervention that included elements of the control group's regimen, while the control group received standard health education and dietary guidance interventions through the use of a digital table method. The assessment of pain scales (VAS), self-rating depression scales (SDS), self-rating anxiety scales (SAS), and complication rates were all part of the postoperative follow-up. RESULTS: At seven days following surgery, there were no appreciable variations in the observation and control groups' VAS, SAS, and SDS scores (P > 0.05). Nevertheless, the observation group showed significantly lower VAS and SAS scores than the control group at 6 months and 1 year following surgery (P < 0.05). The observation group's SDS score was significantly lower than the control group's one year after surgery (P < 0.001). In comparison to the control group, the observation group also showed a lower overall complication rate (P < 0.05), especially in the cases of facial herpes and vertigo. COMPARISON WITH EXISTING METHODS: Our ongoing, all-encompassing rehabilitation approach demonstrated better results than current approaches in terms of long-lasting pain alleviation, enhanced mental health, and lower rates of complications in patients with trigeminal neuralgia following surgery. This implies that, in comparison to traditional methods, incorporating rehabilitation strategies may provide greater therapeutic benefits. CONCLUSION: Continuous comprehensive rehabilitation intervention can effectively reduce the degree of postoperative pain in patients with trigeminal neuralgia, help to regulate their psychological state, and reduce the occurrence of complications, which has certain clinical application value.

Causal interactions in brain networks predict pain levels in trigeminal neuralgia.

Trigeminal neuralgia (TN) is a highly debilitating facial pain condition. Magnetic resonance imaging (MRI) is the main method for generating insights into the central mechanisms of TN pain in humans. Studies have found both structural and functional abnormalities in various brain structures in TN patients as compared with healthy controls. Whereas studies have also examined aberrations in brain networks in TN, no studies have to date investigated causal interactions in these brain networks and related these causal interactions to the levels of TN pain. We recorded fMRI data from 39 TN patients who either rested comfortably in the scanner during the resting state session or tracked their pain levels during the pain tracking session. Applying Granger causality to analyze the data and requiring consistent findings across the two scanning sessions, we found 5 causal interactions, including: (1) Thalamus → dACC, (2) Caudate → Inferior temporal gyrus, (3) Precentral gyrus → Inferior temporal gyrus, (4) Supramarginal gyrus → Inferior temporal gyrus, and (5) Bankssts → Inferior temporal gyrus, that were consistently associated with the levels of pain experienced by the patients. Utilizing these 5 causal interactions as predictor variables and the pain score as the predicted variable in a linear multiple regression model, we found that in both pain tracking and resting state sessions, the model was able to explain ∼36 % of the variance in pain levels, and importantly, the model trained on the 5 causal interaction values from one session was able to predict pain levels using the 5 causal interaction values from the other session, thereby cross-validating the models. These results, obtained by applying novel analytical methods to neuroimaging data, provide important insights into the pathophysiology of TN and could inform future studies aimed at developing innovative therapies for treating TN.

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OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Pregabalin-induced delayed cutaneous hypersensitivity reaction occurring after 40 days of use: a case report.

Pregabalin is the first-line treatment for neuropathic pain. Cases of cutaneous hypersensitivity reactions caused by pregabalin generally occur within 2 weeks of initiating medication. We report a rare case of a delayed cutaneous hypersensitivity reaction caused by pregabalin, which was confirmed by a drug provocation test. A 72-year-old man with severe herpes zoster neuralgia developed maculopapular drug eruption covering 80% to 90% of his total body surface area after 40 days of combined multidrug analgesia. A drug provocation test for pregabalin was positive. The time interval between initiating medication and the onset of the patient's rash was the longest and he also had the largest area of skin affected compared with patients with a similar condition in previous related reports. Remaining vigilant for possible adverse cutaneous hypersensitivity reactions during treatment is important because of the long-term course of pregabalin treatment for neuropathic pain.

Conservative Management of Trigeminal Neuralgia and Degenerative Cervical Myelopathy: A Case Report.

It is hypothesized that degenerative cervical myelopathy (DCM) may induce or exacerbate trigeminal neuralgia (TN) through mechanisms such as direct compression of the spinal trigeminal tract, inflammation, or vascular issues, leading to ischemia within cervical segments C3-C4, where the spinal trigeminal nucleus extends. Here, we report the potential therapeutic impact of chiropractic treatment in a 55-year-old female with TN resistance to medical therapy and DCM. The patient received targeted chiropractic care, consisting of high-velocity, low-amplitude (HVLA) spinal manipulation of the C3-C7 and T1-T4 vertebral segments to address joint dysfunction, coupled with intermittent mechanical cervical traction for 20-minute sessions, and focused radial shockwave therapy aimed at myofascial trigger points within the trapezius and levator scapulae muscles. After initiating the chiropractic care plan, the patient experienced a significant reduction in the frequency and severity of TN pain, which persisted throughout the treatment period. Notably, this alleviation in symptoms was maintained at the six-month follow-up, suggesting a sustained therapeutic effect rather than a transient improvement. The lasting nature of the pain reduction provides a compelling argument for the long-term benefits of chiropractic intervention in the management of TN, particularly in cases with concurrent DCM.

Peripheral Nerve Stimulation for a Refractory Case of Postherpetic Neuralgia in the Upper Limb: A Case Report.

Postherpetic neuralgia (PHN) is a chronic neuropathic pain syndrome that is a direct consequence of the reactivation of varicella zoster virus (VZV). It manifests as neuropathic pain, which is pain that occurs because of dysfunction or damage of the nerves that carry sensations to the brain, and this typically persists for months to years after herpes zoster. Current conservative management for PHN includes a combination of topical agents (i.e., lidocaine and capsaicin) and systemic therapy (i.e., serotonin and norepinephrine reuptake inhibitors (SNRIs), gabapentin, pregabalin, and opioids). For refractory cases, with persistent intractable pain, more invasive interventional techniques can be used as pain-relieving measures to improve the patient's quality of life. This report presents a patient with upper limb PHN who responded to peripheral nerve stimulation (PNS) after he failed to obtain sufficient pain relief with conservative management.

Accuracy of augmented reality-guided needle placement for pulsed radiofrequency treatment of pudendal neuralgia: a pilot study on a phantom model.

Background: Pudendal neuralgia (PN) is a chronic neuropathy that causes pain, numbness, and dysfunction in the pelvic region. The current state-of-the-art treatment is pulsed radiofrequency (PRF) in which a needle is supposed to be placed close to the pudendal nerve for neuromodulation. Given the effective range of PRF of 5 mm, the accuracy of needle placement is important. This study aimed to investigate the potential of augmented reality guidance for improving the accuracy of needle placement in pulsed radiofrequency treatment for pudendal neuralgia. Methods: In this pilot study, eight subjects performed needle placements onto an in-house developed phantom model of the pelvis using AR guidance. AR guidance is provided using an in-house developed application on the HoloLens 2. The accuracy of needle placement was calculated based on the virtual 3D models of the needle and targeted phantom nerve, derived from CBCT scans. Results: The median Euclidean distance between the tip of the needle and the target is found to be 4.37 (IQR 5.16) mm, the median lateral distance is 3.25 (IQR 4.62) mm and the median depth distance is 1.94 (IQR 7.07) mm. Conclusion: In this study, the first method is described in which the accuracy of patient-specific needle placement using AR guidance is determined. This method could potentially improve the accuracy of PRF needle placement for pudendal neuralgia, resulting in improved treatment outcomes.

Letter to the editor: "A nomogram based on radiomics and clinical information to predict prognosis in percutaneous balloon compression for the treatment of trigeminal neuralgia: a retrospective cohort study of published cases".

This critique evaluates a recent study on a nomogram based on radiomics and clinical data to predict the prognosis of percutaneous balloon compression (PBC) for trigeminal neuralgia (TN), focusing on its strengths, weaknesses, and suggestions for future research. It acknowledges the innovative approach's potential to personalize treatment and improve outcomes, but raises concerns about the study's retrospective nature, sample size limitations, and challenges in implementing radiomics in clinical practice. Overall, although the nomogram offers promise, further validation in larger cohorts is essential to confirm its utility and reliability. Future research should prioritize prospective multicenter studies with standardized protocols, collaborative efforts among institutions, and innovative techniques to advance our understanding and management.

Compared to oxcarbazepine and carbamazepine, botulinum toxin type A is a useful therapeutic option for trigeminal neuralgia symptoms: A systematic review.

OBJECTIVES: This review aimed to compare the effectiveness of three treatments: BTX A, CBZ, and OXB, in managing trigeminal neuralgia (TN). MATERIAL AND METHODS: We conducted a thorough search for research articles related to our issue using specific keywords on several databases, including Cochrane Central Register of Controlled Trials, Science Direct, Scopus, PubMed, Elsevier, Springer Journals, Ovid Medline, EBSCO, and Web of Science. Our focus was on publications from 1965 to 2023. RESULTS: We retrieved 46 articles from the search and reviewed them carefully. Out of these, we selected 29 articles that met the inclusion criteria. Among the selected articles, 11 investigated the effects of CBZ and OXB, while 18 explored the impact of BTX A on the improvement of TN symptoms. The response rate ranged between 56% and 90.5% for CBZ and between 90.9% and 94% for OXB. The response rate for BTX A ranged between 51.4% and 100%. All these three treatments had a remarkable effect on the improvement of TN. Importantly, findings highlighted that side effects of CBZ and OXB could lead to treatment discontinuation in some cases, whereas BTX A's side effects have been minimal and less frequent. CONCLUSIONS: Consequently, BTX A emerges as a promising alternative for TN treatment. However, additional clinical trials are necessary to validate this finding, and further research is required to establish a standardized protocol for administering BTX A in TN.

The white matter characteristic of the genu of corpus callosum coupled with pain intensity and negative emotion scores in patients with trigeminal neuralgia: a multivariate analysis.

Background: Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder that not only causes intense pain but also affects the psychological health of patients. Since TN pain intensity and negative emotion may be grounded in our own pain experiences, they exhibit huge inter-individual differences. This study investigates the effect of inter-individual differences in pain intensity and negative emotion on brain structure in patients with TN and the possible pathophysiology mechanism underlying this disease. Methods: T1 weighted magnetic resonance imaging and diffusion tensor imaging scans were obtained in 46 patients with TN and 35 healthy controls. All patients with TN underwent pain-related and emotion-related questionnaires. Voxel-based morphometry and regional white matter diffusion property analysis were used to investigate whole brain grey and white matter quantitatively. Innovatively employing partial least squares correlation analysis to explore the relationship among pain intensity, negative emotion and brain microstructure in patients with TN. Results: Significant difference in white matter integrity were identified in patients with TN compared to the healthy controls group; The most correlation brain region in the partial least squares correlation analysis was the genus of the corpus callosum, which was negatively associated with both pain intensity and negative emotion. Conclusion: The genu of corpus callosum plays an important role in the cognition of pain perception, the generation and conduction of negative emotions in patients with TN. These findings may deepen our understanding of the pathophysiology of TN.

The Postconcussion Syndrome and Posttraumatic Headaches in Civilians, Soldiers, and Athletes.

Posttraumatic headaches are one of the most common and controversial secondary headache types. After a mild traumatic brain, an estimated 11% to 82% of people develop a postconcussion syndrome, which has been controversial for more than 160 years. Headache is estimated as present in 30% to 90% of patients after a mild head injury. Most headaches are tension-type-like or migraine-like. Headaches in civilians, soldiers, athletes, and postcraniotomy are reviewed. The treatments are the same as for the primary headaches. Persistent posttraumatic headaches can continue for many years.

Trigeminal and Glossopharyngeal Neuralgia.

Trigeminal neuralgia and glossopharyngeal neuralgia are craniofacial pain syndromes characterized by recurrent brief shock-like pains in the distributions of their respective cranial nerves. In this article, the authors aim to summarize each condition's characteristics, pathophysiology, and current pharmacotherapeutic and surgical interventions available for managing and treating these conditions.

Occipital nerve stimulation in pediatric patients with refractory occipital neuralgia.

PURPOSE: Occipital neuralgia (ON) is a disabling problem within the pediatric population. Many of these patients fail medical therapies and continue to suffer without further surgical management. Occipital nerve stimulation (ONS) is used to treat ON in the adult population leading to a 72-89% reduction in pain; however, there are limited studies regarding its use in the pediatric population. In this study, we examined the outcomes of ONS in pediatric patients with medically refractory ON. METHODS: We performed a chart review of pediatric patients at our institution who have undergone ONS for the same indications. RESULTS: We identified 3 patients at our institution who underwent ONS trial and/or permanent implantation for ON. One patient had complete pain relief after the trial and declined permanent implantation. The other patient had fewer attacks compared to his pre-trial baseline and controlled them by adjusting his permanent implant stimulation settings. The last patient had near complete relief of her symptoms and no longer required any pain medication. CONCLUSION: Our study highlights the paucity of studies evaluating the utility of ONS in the pediatric ON population. Limited data from both the literature and our institution's experience reveal that pediatric patients may benefit from trial and/or permanent implantation of ONS for medically refractory ON pain.

Ganglionic Local Opioid Analgesia at the Superior Cervical Ganglion: MRI-Verified Solution Spread.

INTRODUCTION: Ganglionic local opioid analgesia (GLOA) at the superior cervical ganglion (SCG) is performed for pain control and is known to be an effective procedure. In this study, we evaluated the spread of the injectate in the area of the SCG. Our expectation was that there would be a correlation between the area and volume of the injectate spread and post-procedural outcome measures. METHODS: This was a retrospective blinded review of magnetic resonance imaging (MRI) scans. Assessors evaluated the anatomical area of fluid spread, the furthermost spread from midline, any hampered spread and contact of contrast fluid with other structures. The efficacy of GLOA and complications were estimated. RESULTS: The main solution spread reached from the C1 to C3 vertebrae. The furthest spread in the lateral and sagittal planes was 21.2 and 15.2 mm, respectively. The furthest craniocaudal spread was 63.5 mm. In 53.3% and 33% of interventions, the solution was found in the parapharyngeal space and in its "medial compartment," respectively. A correlation was found between pain relief and both solution spread and volume of solution spread. No hampered spread was recorded. A negative correlation between pain reduction and number of GLOA was observed. Higher pre-procedural pain intensity was correlated with higher pain reduction. We estimated pain relief in 93% of procedures correctly. No correlation between post-procedural Numerical Rating Scale (NRS) scores and different needle approaches was found. CONCLUSION: For the transoral blocking technique, a strict laterodorsal needle direction is recommended to prevent possible block failures. A total volume of 2 ml injected into the parapharyngeal space and its "medial compartment" is recommended. Higher volumes may lead to uncontrolled distribution patterns. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT05257655; date of registration 2022-02-25; patient enrollment date from 2023-01-09 to 2023-08-31.

The injection of low-dose opioids (mainly buprenorphine or sufentanil) to different sympathetic ganglia has been termed "ganglionic local opioid analgesia" (GLOA). This form of therapy has been successfully used for numerous, often protracted diseases that severely impair the patient's quality of life, such as trigeminal neuralgia. For example, as part of a multimodal approach for pain management, GLOA at the superior cervical ganglion should be considered for pain treatment in patients suffering from trigeminal neuralgia with high pre-procedural pain scores.

Efficacy and Challenges: Minimally Invasive Procedures for Trigeminal Neuralgia Treatment in Multiple Sclerosis - A Systematic Review and Meta-Analysis.

INTRODUCTION: Trigeminal neuralgia (TGN) poses a therapeutic challenge, particularly within the context of multiple sclerosis (MS). This study aimed to conduct a comprehensive meta-analysis and systematic review of four less-invasive treatment modalities for TGN in MS patients, namely, gamma knife radiosurgery (GKRS), glycerol rhizotomy (GR), balloon compression (BC), and radiofrequency ablation (RFA). METHODS: Single-armed meta-analyses were employed to assess the overall efficacy of each treatment, while double-armed analyses compared the efficacy between different treatment options in double-armed studies. Outcome evaluations included acute pain relief (within 1 month post-procedure), recurrence rates throughout 18 months of follow-up, and reported complication rates. RESULTS: The meta-analysis revealed diverse outcomes for each intervention. GKRS demonstrated favorable outcomes, achieving a 77% success rate in alleviating pain among a pooled cohort of 863 patients, reinforcing its status as a viable therapeutic option. Additionally, GR, BC, and RFA exhibited efficacy, with success rates of 77%, 71%, and 80%, respectively, based on outcomes observed in 611, 385, and 203 patients. Double-armed analyses highlighted distinctions between the treatments, providing nuanced insights for clinical decision-making. CONCLUSION: This meta-analysis provides a comprehensive overview of less-invasive treatments for TGN in MS patients. GKRS emerges as a leading option with comparable efficacy and fewer complications. However, the study underscores the nuanced efficacy and considerations associated with GR, BC, and RFA. The findings offer valuable insights for clinicians navigating treatment choices in this challenging patient population, considering acute pain relief, recurrence rates, and complication profiles.

Modeling an evaluation of the efficacy of the novel neuroanalgesic drug mirogabalin for diabetic peripheral neuropathic pain and postherpetic neuralgia therapy.

Diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN) are challenging and often intractable complex medical conditions, with a substantial impact on the quality of life. Mirogabalin, a novel voltage-gated Ca2+ channel α2δ ligand, was approved for the indication of DPNP and PHN. However, the time course of effects has not yet been clarified.We aimed to establish pharmacodynamic and placebo effect models of mirogabalin and pregabalin in DPNP and PHN, and to quantitatively compare the efficacy characteristics (maximum efficacy, onset time, and other pharmacodynamic parameters) and safety of mirogabalin and pregabalin. Public databases were comprehensively searched for randomized placebo-controlled clinical trials. A model-based meta-analysis (MBMA) was developed to describe the time course of drug efficacy and placebo effects. Adverse events were compared using a fixed-effects meta-analysis. Sixteen studies including 5,147 participants were eligible for this study. The placebo effect was relatively high and gradually increased with time, and it required at least eight weeks to reach a plateau. The pharmacodynamic model revealed that the maximum pure efficacy for mirogabalin and pregabalin was approximately -7.85% and -8.86%, respectively; the efficacy of mirogabalin to relieve DPNP and PHN was not superior to that of pregabalin, and both drugs had similar safety. While the rate constant of the onset rate of pregabalin was approximately thrice as high as that of mirogabalin. In addition, the baseline level of pain was an important factor affecting pregabalin efficacy. These findings are helpful in evaluating the clinical extension value of mirogabalin. They suggest that the high placebo effect and the baseline level of pain should be considered when grouping patients in future research and development of voltage-gated Ca2+ channel neuroanalgesic.