Branch Of Trigeminal Nerve Research Articles

Electroacupuncture on the Ophthalmic Branch of the Trigeminal Nerve Affects Cerebral Blood Flow in the Frontopolar Cortex During Mental Arithmetic: A Randomized Crossover Trial

Objective: The aim of this study was to examine the effect of cerebral blood flow (CBF) in the frontopolar cortex (FPC) during mental arithmetic tasks by 0.2 mA electroacupuncture (EA) stimulation of the trigeminal nerve's ophthalmic branch. Materials and Methods: This study was a crossover, randomized clinical trial. The participants (19) were divided into a control and an EA group, and both groups performed 10-minute mental-arithmetic tasks. Subsequently, the control group was seated for 5 minutes, while the EA group received EA stimulated at 0.2 mA, 100 Hz, for 5 minutes. Then, the mental-arithmetic tasks were repeated. The primary outcome was oxygenated hemoglobin (OxyHb) levels in the FPC during the mental-arithmetic tasks. Data from 15 of the original 19 participants were analyzed. Results: EA stimulation elevated OxyHb levels significantly. In the right FPC, this occurred in channel (Ch) 4 and 6 (P < 0.05) and Ch 3 (P < 0.01). In the left FPC, this occurred in Ch 10 and 15 (P < 0.05) and Ch 11 and 14 (P < 0.01). EA stimulation affected Ch 11 especially. There was also a significant positive correlation between OxyHb levels during the mental-arithmetic tasks in Ch 11 and changes in the numbers of answers and correct answers (ρ = 0.48; P < 0.05). Conclusions: These results suggest that 0.2 mA EA stimulation increased OxyHb levels in the FPC, particularly associated with increased CBF in the left FPC. Furthermore, the OxyHb levels in the left FPC positively correlated with the changes in the numbers of answers and correct answers.

Our treatment methods in herpes zoster and postherpetic neuralgia: Retrospective analysis

Aim: The aim of this study is to investigate the effectiveness of our treatment methods applied in the pain management of patients with HZ, PHN and risk factors associated with the development of HZ and PHN . Materials and Methods: The study was conducted in our hospital pain medicine clinic. The demographic data of the patients, in which phase of the disease they admitted, in which dermatomes the disease was occurred, what medical treatments they received and type of interventional treatments were applied between the dates January 2019 – January 2023 were recorded. Also, pain reduction was evaluated as beneficial when there’s a reduction in the pain level equal or more than % 50, and below as useless. The dosage scheme and types of drugs used were recorded. The follow-up interval was determined as 6 weeks after the intervention. Results: While 131 (56.2 %) of 233 patients were diagnosed with HZ, 102 patients (43.8%) were diagnosed as PHN. The median age was significantly higher in the PHN group (p&lt;0.001). Thoracic region (60.9%) is the most frequently involved dermatome for HZ and PHN, followed by lumbar, trigeminal nerve ophthalmic branch and cervical region. The most commonly used agents are pregabalin, tramadol and gabapentin, respectively. Interventional treatments, on the other hand, were generally effective regardless of the phase. Conclusion: It has been determined sympathetic blocks and epidural injections in acute and subacute periods are more effective, and peripheral nerve blocks are effective in both periods. While it was found to be effective the pulse radiofrequency in lumbar region, it was found to be effective in the chronic period while it was not effective in the facial dermatome in the acute period.

Peripheral nerve pulsed radiofrequency for trigeminal neuralgia treatment: Is it an effective method?

Trigeminal neuralgia is a paroxysmal and shock-like pain in the trigeminal nerve area. Various treatment options have been used for trigeminal neuralgia such as medical treatment, interventional procedures, and surgical operations. Pulsed radiofrequency (PRF) is a minimally invasive percutaneous technique which seems to be safer and easier to perform. This retrospective study aims to evaluate the analgesic effect, duration of efficacy, and side effects of PRF procedures in the peripheral branches of the trigeminal nerve. The data of the patients with trigeminal neuralgia who were followed up in our hospital's algology clinic from 2016 to 2018 were reviewed retrospectively. Patients aged between 18 and 70 who did not respond to medical treatment or could not use medication due to side effects were treated with PRF procedure for peripheral branches of trigeminal nerve that was selected for this study. Demographic profile, clinical presentation, pain intensity, duration of efficacy, and complications were evaluated from their files. Twenty-one patients who underwent ultrasonography guided PRF procedures were included the study. Mean visual analog scale value of the patients was found to have decreased from 9.25±0.63 to 1.55±0.88 at the end of the 1st month (p<0.001). The painless period for the patients lasted up to 12 (9-21) months and no complications occurred. PRF procedure seems to be an effective and safe method in patients who respond to block of the peripheral branches of the trigeminal nerve.

Trigeminal Sensory Neuropathy Predicts Chemosensory Dysfunction After Skull Base Surgery.

Trigeminal sensory neuropathy, characterized by diminished or exaggerated/painful sensation along the distribution of trigeminal branches, is one of the complications after skull base surgery. These procedures can also affect chemosensory functions and compromise the patients' quality of life. To examine those postoperative complications in chemosensory and facial cutaneous sensory functions as well as their interaction. A total of 61 patients being operated for various pathologies in the vicinity of trigeminal pathway (17 with trigeminal neuralgia, 20 with meningiomas, and 24 with vestibular schwannomas) and 50 healthy controls were enrolled in this case-control study. Postoperative trigeminal neuropathic symptoms were evaluated. The olfactory, gustatory, and intranasal trigeminal functions were assessed using the Sniffin' Stick olfactory test, lateralized taste strip test, and the lateralized intranasal trigeminal CO 2 detection thresholds, respectively. Patients with trigeminal neuralgia and meningioma had relatively decreased olfactory function, whereas those with vestibular schwannoma had a relative decrease in taste function. As for the relationship between the distribution of trigeminal neuropathy and chemosensory dysfunction, we found that V3 involvement predicted lower side-specific taste function. In addition, V2/V3 involvement predicted relatively lower side-specific intranasal trigeminal function. The present results suggest a differential involvement of the chemical senses in relation to the site and pathology of the lesions after surgery. The presence of trigeminal neuropathy is associated with taste and intranasal trigeminal dysfunction. The results serve as a basis for consultation regarding outcome prediction and patient education.

Atypical Facial Pain Treatment With Peripheral Nerve Field Stimulation Using a Micro-Implantable and External Battery Impulse Generator

Atypical facial pain (AFP) is continuous, deep, poorly localized, often initiated by facial trauma or surgery and can involve multiple trigeminal nerve branches. Poor response to medical treatment is often found and ablative invasive procedures has been classically discouraged due to fear of worsening AFP symptoms. Peripheral nerve field stimulation (PNFS) is an emerging treatment for AFP but the optimal stimulation parameters are still being investigated. Pulse generator placement for craniofacial PNFS is usually in the infraclavicular region which can cause discomfort and is cosmetically disadvantageous.

Topographic and Morphometric Study of the Foramen Spinosum of the Skull and Its Clinical Correlation.

Background and Objectives: The spinous foramen (FS) of the skull is an opening located in the greater wing of the sphenoid bone at the base of the skull, and it includes the middle meningeal vessels and the meningeal branch of the mandibular trigeminal nerve. The FS is commonly used as an anatomical landmark in neurosurgical procedures and neuroimaging of the middle cranial fossa because of its relationship with other cranial foramina and surrounding vascular and nervous structures. Thus, specific knowledge of its topography and possible anatomical variations is important regarding some surgical interventions and skull imaging. The aim of this study was to provide further details on the morphology of the FS of the skull by evaluating its topographic and morphometric relationships and correlating the findings with clinical practice. Materials and Methods: Thirty dried skulls of human skeletons from body donors from the collection of the Laboratory of Anatomical Microdissection at a medical school were used. The metric dimensions and variations of the FS and its relationship with adjacent bone structures were analyzed with an interface digital microscope. Results: The results showed the bilateral presence of the FS in all skulls; however, differences were observed in the shape, diameter, and topography in relation to the foramen ovale and the spine of the sphenoid. The FS was present in the greater wing of the sphenoid bone; however, in one skull, it was located in the lateral lamina of the pterygoid process. The FS was smaller than the foramen ovale. A round and oval FS shape was the most common (42.1% and 32.8% of the samples, respectively), followed by drop-shaped (12.5%) and irregular-shaped (12.5%) foramina. Conclusions: In conclusion, FS variations among individuals are common and must be considered by surgeons during skull base interventions in order to avoid accidents and postoperative complications.

A Novel Sublabial Anterior Transmaxillary Approach for Medically Refractory Mesial Temporal Lobe Epilepsy: A Comparative Anatomic Study.

Current approaches for mesial temporal lobe epilepsy may result in suboptimal seizure control and cognitive decline. An incomplete treatment of the epileptogenic zone and unnecessary violation of functional cortical and subcortical areas may contribute to suboptimal results. To describe and test the anatomic feasibility of a novel endoscopic anterior transmaxillary (ATM) approach to the temporal lobe and to compare the described technique to other transfacial approaches. Twenty-four cadaveric brain hemispheres fixed in formalin were used to study anterior temporal surface anatomy. Two additional hemispheres were fixed in formalin and then frozen for white matter dissections. Subsequently, bilateral dissections on 4 injected cadaveric heads were used to describe the endoscopic ATM approach and to evaluate various anterior endoscopic corridors for the temporal pole and mesial temporal lobe structures. The ATM approach was considered superior because of direct visualization of the temporal pole and natural alignment with the mesial temporal structures. The mean exposure corridor covered 49.1° in the sagittal plane and 66.2° in the axial plane. The ATM allowed direct access lateral to the maxillary and mandibular nerves with an anterior-posterior trajectory aligned to the longitudinal axis of the hippocampus formation, allowing for a selective amygdalohippocampectomy with preservation of the trigeminal branches and the lateral temporal neocortex. The ATM approach is anatomically feasible, providing a direct and selective approach for the temporal pole and mesial temporal lobe structures, with a substantial angle of visualization because of its direct alignment with the mesial temporal lobe structures.

Case report: a paroxysmal hemicrania responsive to verapamil

Introduction Paroxysmal hemicrania (PH), a trigeminal autonomic headache, is characterized by unilateral pain in the orbital, supraorbital, and temporal regions, accompanied by nasal congestion and ocular hyperemia, with a predominance (not exclusively) in women, with attacks lasting 2 to 30 minutes and occurring several times daily. Pain crises have been known to cease completely or almost completely with the use of indomethacin. However, in some patients, the side effects caused by taking the drug prevent continuation of treatment. There is also the possibility of a partial response to the first-line drug. In these cases, alternative drugs are chosen, with verapamil being one of the drugs of choice. Objectives In this report, we present a case of a patient with a partial response to the first-line drug therapy and good responsiveness to verapamil. Methods We collected patient data through the electronic medical record. Afterward, we reviewed the literature regarding paroxysmal hemicrania and its responsiveness to indomethacin and verapamil. Results A 56-year-old woman presented with a 1-year history of throbbing pain in the left hemiface, and retro-orbital and temporal ipsilateral pain, lasting approximately 30 minutes with a frequency of 5-6 episodes per day and a maximum remission period of 3 months. The headache attacks were associated with nasal congestion and allodynia and had worsened recently. Her medical history was positive for major depressive disorder and hypertension. At the time she presented, she was taking carbamazepine 900 mg per day, which resulted in partial relief of pain. Clinical examination revealed pain on palpation of the trigeminal branches on the left side, bilateral temporomandibular pain, and pain on palpation of the right greater occipital nerve. Magnetic resonance angiography of the head showed no abnormalities... (Too see the complet abstract, please, check out PDF.)

CT-guided radiofrequency ablation of the extracranial cranial nerve for the treatment of Meige's syndrome.

BackgroundMeige’ s syndrome, a rare form of dystonia, lacks effective treatment. The purpose of this study was to determine the effects of CT-guided percutaneous extracranial radiofrequency ablation of the facial and/or trigeminal nerves in the treatment of Meige’s syndrome.MethodsA total of 10 patients were enrolled in this study, with the numbers of blepharospasm dystonia syndrome (BDS), oromandibular dystonia syndrome (ODS), and blepharospasm combined with oromandibular dystonia syndrome (B-ODS) being 7, 1, and 2, respectively. BDS patients underwent radiofrequency ablation of the bilateral stylomastoid foramen facial nerve; ODS patients underwent radiofrequency ablation of the bilateral foramen oval trigeminal mandibular branch, and B-ODS patients underwent radiofrequency ablation of the bilateral stylomastoid foramen facial nerve and foramen oval trigeminal mandibular branch. The therapeutic effects and complications were observed.ResultsAll 10 patients in this series experienced improved Meige’s syndrome-related symptoms after extracranial radiofrequency ablation of the cranial and/or mandibular branches of the extracranial trigeminal nerve. Adverse events included class II–III facial paralysis and/or mandibular skin numbness. Two patients had recurrences at the 18th and 22nd months postoperatively, respectively; the other patients were being followed up.ConclusionThese results shown that CT-guided radiofrequency ablation of bilateral stylomastoid foramen facial nerve and/or oval foramen trigeminal mandibular branch can effectively treat the corresponding types of Meige’s syndrome. According to preliminary observations, the therapeutic effect may last more than 18 months.

INVERSE MARCUS GUNN SYNDROME – A RARE FACIAL SYNKINESIS

Marcus gunn syndrome is one of the most common variety of oculofacial synkinesis. It is seen in 4-6% of congenital ptosis patients. An aberrant neural misdirection appears to exist between motor branch of trigeminal (CN V3) nerve innervating the external pterygoid muscle and fibers of the superior division of oculomotor nerve (CN 3) that innervate the levator palpebrae superioris. Inverse Marcus Gunn syndrome, a very rare variant of synkinesis characterized by lid drooping on masticatory movement and opening of mouth due to the misfiring between 3rd and 5th cranial nerve. An 8-year-old male child presented with congenital ptosis with anomalous drooping of upper lid while eating or opening of mouth.

Trigeminal‐mediated headshaking: A diagnostic challenge

Trigeminal‐mediated headshaking: A diagnostic challenge

The Focus and New Progress of Percutaneous Balloon Compression for the Treatment of Trigeminal Neuralgia.

Trigeminal neuralgia is a condition confined to the trigeminal nerve, causing one or more branches of facial nerve pain. Surgical treatment options for trigeminal neuralgia include microvascular decompression(MVD), percutaneous balloon compression (PBC), radiofrequency thermocoagulation(RF), percutaneous retrogasserian glycerol rhizotomy(PRGR), gamma knife, etc. Of these treatments, PBC is increasingly being used by clinicians for trigeminal neuralgia. PBC is a simple surgical operation performed to treat trigeminal neuralgia. Owing to its advantages, PBC is favored by many clinicians. In this study, we aimed to emphasize the need to analyze the shape of the balloon, position, compression time, and pressure, as these factors can affect the efficacy of PBC. The relief of pain by balloon compression is related to the shape of the balloon on X-ray, which is the key to the operation. Owing to continued progress and advances in current imaging technologies, clinicians revealed that the precise positioning of the foramen ovale is no longer an intraoperative problem. Instead, the anatomy of Meckel’s cave and the shape of the balloon must be the focus to achieve the best treatment effect. For clinicians, PBC is simple and is associated with a short operation time. PBC also has other advantages, such as low cost and immediate postoperative pain relief. The recurrence rate of pain post-PBC is low, despite the occurrence of facial numbness post-op. However, this side effect is reversible and does not affect daily life of the patient. In fact, the patient can be discharged 1–2 days after surgery. Overall, PBC can be considered as one of the preferred surgical methods for the treatment of primary trigeminal neuralgia. In this paper, we explain the main points of PBC operation in detail in terms of Meckel’s cave, surgical procedure, complications, discussion of the focus and new progress, etc.

Design and Developing a Device for Migraine Treatment: A Review

Migraine is usually somatosensory input to the head involving pseudo-unipolar trigeminal and upper cervical branches. It is a very common disorder involving visual perception difficulties, thereby causing cognitive decline. Advancement in migraine treatment is always a crucial point of research for every neuro-ophthalmologist.Results: Many novel treatment approaches have received Food and Drug Administration approvals for well-outlined therapies in migraine treatment. In this review, we summarize this treatment methodology and prototype a device that can cater to the limitations of already available migraine treatment devices in the market. Many novel and stirring therapies continue to evolve for the therapy of migraine. Though highly advanced and sophisticated, this therapy gets knock-down due to many limitations. This limitation renders them from being effective. Being on track with this commonly occurring disorder is important in reducing the disability from it.

Radiofrequency thermoablation of the peripheral branches of trigeminal nerve versus the Gasserian ganglion for treating idiopathic trigeminal neuralgia: A systematic review and meta-analysis

BackgroundTrigeminal neuralgia is characterized by pain at the distribution of one or more of the trigeminal nerve branches and is usually treated with anti-epileptic medication. When first line treatment fails, patients receive other treatment modalities including radiofrequency thermoablation (RFT) of the Gasserian ganglion and peripheral branches of the trigeminal nerve. The aim of this study is to compare RFT of the Gasserian ganglion and peripheral branches of trigeminal nerve in terms of efficacy and rate of complications. MethodsThis was a systematic review and meta-analysis that searched Medline, Cochrane Central Register of Controlled Trials, and Embase using Medical Subject Headings and the references of the enrolled studies with no restriction on date. We included only RCTs that compared the RFT of the Gasserian ganglion and peripheral branches of trigeminal nerve with one of the following outcomes: pain scales, immediate effective rate, recurrence rate, and complications. ResultsFive articles were eligible for our review and showed that there was no difference between RFT of the peripheral nerves and the Gasserian ganglion in terms of pain scores. There was a non-significant trend for RFT of the peripheral nerve to have higher immediate effect rates and higher recurrence rates. RFT of the Gasserian ganglion group was associated with masticatory weakness, while the other group was associated with facial swelling and numbness of V2. ConclusionRFT of the peripheral branches is a safe and effective method to treat idiopathic trigeminal neuralgia but leads to a higher recurrence rate when compared with RFT of the Gasserian ganglion.

Mechanistic contribution of CaV3.2 calcium channels to trigeminal neuralgia pathophysiology not clarified

Trigeminal neuralgia (TN) is a rare, yet debilitating trigeminal pain disorder, with jolts of supramaximal-debilitating pain in one or more of the three trigeminal branches. Familial TN is now recognized, with a recent report describing several human genetic polymorphisms. One affected gene is the voltage-gated calcium channel, CaV3.2 (CACNA1H), with 19 polymorphisms first described. A recent study in PAIN by Gambeta-et-al (DOI:10.1097/j.pain.0000000000002651) is entitled "CaV3.2 calcium channels contribute to trigeminal neuralgia ". Here, I call into question their claim. My main arguments are 1)-3): 1) Gambeta-et-al studied 4/19 mutations reported in heterologous cellular expression, with two mutations showing gain-of-function of CaV3.2, two mutations not showing gain-of-function. Therefore the exemplary picks of familial TN-associated CaV3.2 mutations do not show a uniform change of channel function, such as gain-of-function. 2) In Gambeta-et-al, one gain-of-function mutation, CaV3.2(G563R) was directed to mouse trigeminal ganglion (TG) neurons, and their resulting hyperexcitability was demonstrated. A critical control of a non-gain-of-function channel was not included here, it was unclear whether neurons were separated by sex, and human sensory neurons were not used. Importantly, it is not clear that TG neurons are the critical cellular site of CaV3.2 mutations. 3) Gambeta-et-al used CaV3.2-/- pan-null knockout mice. Human TN-associated CaV3.2 mutations were not over-expressed. They used a infraorbital nerve constriction injury and measured facial heat hyperalgesia. CaV3.2-/- show a pain phenotype similar to control, yet are not affected by a CaV3-inhibitory compound, Z944. My argument is that when starting with TN-associated human mutations, use of a trigeminal neuropathic pain model is of limited value, and that human mutations have to be expressed against a mouse null background. Re thermal cue, Gambeta-et-al failed to study cold-evoked pain which is a TN clinical hallmark. Thus, Gambeta-et-al's 2022 PAIN-paper offers little new mechanistic evidence why CaV3.2 polymorphisms are associated with trigeminal neuralgia.

Radiofrequency thermocoagulation combined with doxorubicin injection for treatment of trigeminal neuralgia mandibular branch.

This study aimed to evaluate the clinical application value of 3D printed template-guided radiofrequency thermocoagulation combined with doxorubicin injection for the treatment of trigeminal neuralgia mandibular branch. A total of 50 patients with primary trigeminal neuralgia mandibular branch in the hospital from January 2019 to September 2020 were randomly divided into two groups: 3D printed template-guided radiofrequency thermocoagulation combined with doxorubicin injection was used as the research group (n=25), and 3D printed template guided radiofrequency thermocoagulation was used as the control group (n=25). Comparative analysis of visual analogue score (VAS) was conducted before and immediately after surgery and at 1, 3, 6, and 12 months after surgery. The Brisman efficacy evaluation criteria for trigeminal neuralgia was used to evaluate the therapeutic effect of each postoperative follow-up period, and postoperative complications were observed. The VAS immediately after surgery and at 1, 3, 6, and 12 months after surgery in the two groups was significantly lower than that before surgery, with statistical significance (P<0.05). According to Brisman efficacy evaluation criteria for trigeminal neuralgia, no significant difference was found in the efficacy between the two groups at 1 and 3 months after surgery (P>0.05). At 6 and 12 months postoperatively, the effectiveness of the research group was higher than that of the control group, and the differences were statistically significant (P<0.05). In the research group, no recurrence occurred during the follow-up period, whereas in the control group, one, two, and four recurrences occurred 3, 6, and 12 months after surgery, respectively. No obvious complications were found in both groups. 3D printed template-guided radiofrequency thermocoagulation combined with doxorubicin injection for the treatment of trigeminal neuralgia mandibular branch could enhance the long-term curative effect and reduce the recurrence rate, thus worthy of clinical promotion and application.

Cavernous sinus syndrome: a case report

Background: Cavernous sinus syndrome (CSS) is a rare, but potentially life- and sight-threatening condition. We report a case of multiple cranial neuropathies with CSS.Case presentation: A 70-year-old woman presented with unilateral complete ptosis, ophthalmoplegia, and diplopia. Examination showed left-sided multiple cranial nerve palsies, with the involvement of cranial nerve III (oculomotor nerve), IV (trochlear nerve), V1 and V2 (ophthalmic and maxillary branches of trigeminal nerve), and VI (abducens nerve). A clinical diagnosis of CSS was made. Neuroimaging revealed a left-sided cavernous sinus mass for further investigation.Conclusion: In this case report, we highlight the clinical and radiological features of CSS to raise clinical suspicion for similar diagnosis in the future.

Course of Preexisting Migraine Following Spontaneous Subarachnoid Hemorrhage.

BackgroundOur objective was to observe the course of preexisting migraine following subarachnoid hemorrhage (SAH) in patients with and without craniotomy.MethodsWe designed an exploratory analysis and hypothesis-generating study of prospectively collected data starting by recruiting patients suffering from SAH with the Hunt and Hess scale score of ≤ 4. Out of 994 cases, we identified 46 patients with preexisting active migraine defined by at least four attacks in the year before SAH. According to the treatment, we subdivided the patients into two groups: the first group included patients with surgical aneurysm clipping with transection of the middle meningeal artery (MMA) and accompanying trigeminal nerve branches and the second group included patients with endovascular aneurysm coiling or without any interventional treatment. During the follow-up, we recorded the course of migraine frequency, duration, intensity, and character.ResultsFor both groups (craniotomy n = 31, without craniotomy n = 15), a significant improvement regarding the preexisting migraine during a mean follow-up of 46 months (min. 12 months, max. 114 months) was seen regarding complete remission or at least >50% reduction in migraine attacks (p < 0.001 and p = 0.01). On comparing the groups, this effect was significantly more pronounced in patients with craniotomy (for no recurrence of migraine: p = 0.049). After craniotomy, 77.4% of the patients had no further attacks of migraine headache and 19.4% showed a reduction of >50% while only 2.2% did not report any relevant change. In the non-surgical group, 46.7% had no further migraine attacks, 20% had a reduction of >50%, while no change was noted in 33.3%.ConclusionsOur study provides evidence that the dura mater might be related to migraine headaches and that transection of the MMA and accompanying trigeminal dural nerve branches might disrupt the pathway leading to a reduction of migraine attacks. However, coiling alone ameliorated migraine complaints.

Galcanezumab modulates Capsaicin-induced C-fiber reactivity.

The vasodilatory calcitonin-gene related peptide (CGRP) is understood as pivotal mediator in migraine pathophysiology. Blocking CGRP with small molecules or monoclonal antibodies (CGRP-mAb) reduces migraine frequency. However, prescription of CGRP-mAbs is still regulated and possible predictive measures of therapeutic success would be useful. Using standardized capsaicin-induced dermal blood flow model, 29 migraine patients underwent a laser speckle imaging measurement before and after administration of galcanezumab. At both sessions dermal blood flow before and after capsaicin stimulation as well as flare size were analyzed over all three trigeminal branches and the volar forearm for extracranial control. Long-term measures were repeated in 14 patients after continuous treatment ranging from 6 to 12 months. Resting dermal blood flow remained unchanged after administration of galcanezumab. Capsaicin-induced dermal blood flow decreased significantly after CGRP-mAb in all tested areas compared to baseline and this was consistent even after 12 months of treatment. However, following galcanezumab administration, the flare size decreased only in the three trigeminal dermatomes, not the arm and was therefore specific for the trigemino-vascular system. None of these two markers distinguished between responders and non-responders. CGRP-mAb changed blood flow response to capsaicin stimulation profoundly and this effect did not change over a 12-month application. Neither capsaicin-induced flare nor dermal blood flow can be used as a predictor for treatment efficacy. These data suggest that the mechanism of headache development in migraine is not entirely CGRP-mediated.

Mechanistic contribution of CaV3.2 calcium channels to trigeminal neuralgia pathophysiology not clarified.

Trigeminal neuralgia (TN) is a rare, yet debilitating trigeminal pain disorder, with jolts of supramaximal-debilitating pain in one or more of the three trigeminal branches. Familial TN is now recognized, with a recent report describing several human genetic polymorphisms. One affected gene is the voltage-gated calcium channel, CaV3.2 ( CACNA1H), with 19 polymorphisms first described. A recent study in PAIN by Gambeta-et-al (DOI:10.1097/j.pain.0000000000002651) is entitled " CaV3.2 calcium channels contribute to trigeminal neuralgia ". Here, I call into question their claim. My main arguments are 1)-3): 1) Gambeta-et-al studied 4/19 mutations reported in heterologous cellular expression, with two mutations showing gain-of-function of CaV3.2, two mutations not showing gain-of-function. Therefore the exemplary picks of familial TN-associated CaV3.2 mutations do not show a uniform change of channel function, such as gain-of-function. 2) In Gambeta-et-al, one gain-of-function mutation, CaV3.2(G563R) was directed to mouse trigeminal ganglion (TG) neurons, and their resulting hyperexcitability was demonstrated. A critical control of a non-gain-of-function channel was not included here, it was unclear whether neurons were separated by sex, and human sensory neurons were not used. Importantly, it is not clear that TG neurons are the critical cellular site of CaV3.2 mutations. 3) Gambeta-et-al used CaV3.2-/- pan-null knockout mice. Human TN-associated CaV3.2 mutations were not over-expressed. They used a infraorbital nerve constriction injury and measured facial heat hyperalgesia. CaV3.2-/- show a pain phenotype similar to control, yet are not affected by a CaV3-inhibitory compound, Z944. My argument is that when starting with TN-associated human mutations, use of a trigeminal neuropathic pain model is of limited value, and that human mutations have to be expressed against a mouse null background. Re thermal cue, Gambeta-et-al failed to study cold-evoked pain which is a TN clinical hallmark. Thus, Gambeta-et-al's 2022 PAIN-paper offers little new mechanistic evidence why CaV3.2 polymorphisms are associated with trigeminal neuralgia.