The neural basis of tongue mechanosensation remains largely mysterious despite the tongue\'s high tactile acuity, sensitivity, and relevance to ethologically important functions. We studied terminal morphologies and tactile responses of lingual afferents from the trigeminal ganglion. Fungiform papillae, the taste-bud-holding structures in the tongue, were convergently innervated by multiple Piezo2+ trigeminal afferents, whereas single trigeminal afferents branched into multiple adjacent filiform papillae. In vivo single-unit recordings from the trigeminal ganglion revealed lingual low-threshold mechanoreceptors (LTMRs) with distinct tactile properties ranging from intermediately adapting (IA) to rapidly adapting (RA). The receptive fields of these LTMRs were mostly less than 0.1 mm2 and concentrated at the tip of the tongue, resembling the distribution of fungiform papillae. Our results indicate that fungiform papillae are mechanosensory structures and suggest a simple model that links functional and anatomical properties of tactile sensory neurons in the tongue.

BACKGROUND: Orally administered second-generation gepants are effective for the treatment of migraine. The intranasal administration of the third-generation gepant zavegepant might have additional benefits including a rapid onset of action, but it is not clear yet to which extent this has clinical relevance.
METHODS: We examined the effect of zavegepant on the relaxations induced by calcitonin gene-related peptide (CGRP) in human isolated middle meningeal arteries. Furthermore, we connected the pharmacodynamics and pharmacokinetics of gepants by combining data from clinical and basic research.
RESULTS: We showed that 10 nM zavegepant potently antagonized the functional response to CGRP. We also showed that all gepants are effective at inhibiting functional responses to CGRP at their therapeutic plasma concentrations.
CONCLUSIONS: The relatively low predicted potency of zavegepant to inhibit CGRP-induced relaxation at therapeutic systemic plasma concentrations may point to the relevance of local delivery to the trigeminovascular system through intranasal administration. This approach may have additional benefits for various groups of patients, including overweight patients.

[This corrects the article DOI: 10.3389/fpain.2024.1374929.].

The information provided from the papers reviewed here about the role of epigenetics in chronic craniofacial neuropathic pain is critically important because epigenetic dysregulation during the development and maintenance of chronic neuropathic pain is not yet well characterized, particularly for craniofacial pain. We have noted that gene expression changes reported vary depending on the nerve injury model and the reported sample collection time point. At a truly chronic timepoint of 10 weeks in our model of chronic neuropathic pain, functional groupings of genes examined include those potentially contributing to anti-inflammation, nerve repair/regeneration, and nociception. Genes altered after treatment with the epigenetic modulator LMK235 are discussed. All of these differentials are key in working toward the development of diagnosis-targeted therapeutics and likely for the timing of when the treatment is provided. The emphasis on the relevance of time post-injury is reiterated here.

BACKGROUND: Pediatric headache is an increasing medical problem that has adverse effects on children\'s quality of life, academic performance, and social functioning. Children with primary headaches exhibit enhanced sensory sensitivity compared to their healthy peers. However, comprehensive investigations including multimodal sensory sensitivity assessment are lacking. This study aimed to compare sensory sensitivity of children with primary headaches with their healthy peers across multiple sensory domains.
METHODS: The study included 172 participants aged 6 to 17 years (M = 13.09, SD = 3.02 years; 120 girls). Of these 80 participants were patients with migraine, 23 were patients with tension-type headache, and 69 were healthy controls. The following sensory measures were obtained: Mechanical Detection Threshold (MDT), Mechanical Pain Threshold (MPT), Mechanical Pain Sensitivity (MPS), detection and pain threshold for Transcutaneous Electrical Nerve Stimulation (TENS), olfactory and intranasal trigeminal detection threshold, and odor identification ability. Sensory sensitivity was compared between groups with a series of Kruskal-Wallis tests. Binomial regression models were used to compare the relative utility of sensory sensitivity measures in classifying participants into patients and healthy controls, as well as into patients with migraine and tension-type headache.
RESULTS: Patients with migraine had lower MPT measured at the forearm than patients with tension-type headaches and healthy controls. MPS was higher in patients with migraine than in healthy controls. All patients with headaches had lower detection threshold of TENS and higher olfactory sensitivity. Healthy controls showed increased intranasal trigeminal sensitivity. Scores in MPS, TENS, and olfactory and trigeminal thresholds were significantly predicting presence of primary headaches. Additionally, scores in MPT, olfactory and trigeminal threshold were positive predictors of type of headache.
CONCLUSIONS: Children with primary headaches exhibit different sensory profiles than healthy controls. The obtained results suggest presence of increased overall, multimodal sensitivity in children with primary headaches, what may negatively impact daily functioning and contribute to further pain chronification.
BACKGROUND: The study was registered in the German Registry of Clinical Trials (DRKS) DRKS00021062.

Background  Although medical treatment is the mainstay of therapy, in trigeminal neuralgia (TN), patients failing to respond to it make them candidates to ablative or nonablative procedures. Objective  The aim of this study was to compare the outcome of Microvascular decompression (MVD) and radiofrequency (RF) thermocoagulation in the management of TN affecting the mandibular and maxillary divisions. Materials and Methods  Retrospective analysis of the data of 40 patients suffering from intractable classical TN affecting the maxillary or mandibular divisions or both was carried out. Twenty patients were operated upon by MVD of the trigeminal nerve; and 20 had RF ablation of the maxillary or mandibular divisions of the trigeminal nerve or both. Results  In MVD the overall successful outcome was achieved in 16 patients (80%), while the failure was in 4 patients (20%) of which 3 had a fair outcome and 1 patient had a poor outcome. Whereas in RF the overall successful outcome was achieved in 17 patients (85%), while the failure was in 3 patients (15%) of which 2 had a fair outcome and 1 patient had a poor outcome. Outcome was insignificantly different between both groups ( p -value 0.806). Conclusion  MVD and RF ablation represent safe and efficacious surgical choices for addressing TN that encompasses both the mandibular and maxillary divisions. Long-term follow-up studies demonstrate that MVD consistently yields favorable outcomes, establishing it as the preferred primary surgical technique, unless contraindicated by the patient\'s general health and specific needs.

BACKGROUND: Chemosensory function in pregnant women is far from being fully understood due to the lack of data and inconsistencies between the results of self-reports and objective studies.
METHODS: In the present study in pregnant and non-pregnant women (npregnant = 14, nnon-pregnant = 13), we measured EEG-derived electrophysiological response measures supported by psychophysical olfactory and trigeminal tests.
RESULTS: Results indicate that the olfactory event-related potential amplitudes or latencies of the P1, N1, and P2 components remain unchanged in pregnant women. In accordance with these findings, no difference was observed between pregnant and non-pregnant women in psychophysical olfactory tests. However, pregnant women displayed a lower degree of sensitivity to trigeminal stimuli compared to non-pregnant controls, which was also reflected in the electrophysiological responses to trigeminal stimuli.
CONCLUSIONS: Counterintuitive as they may seem, our findings demonstrate a \"flattening\" of chemosomatosensory responses. Psychological processes occurring during pregnancy, such as changes in socioemotional perception of odors resulting from the diminished stress response, may provide a background to these results. Overall, the present results indicate the absence of major differences between non-pregnant and pregnant women in terms of measured olfactory function though chemosomatosensory function of the pregnant women appears to be decreased.

OBJECTIVE: Tumors located within the Meckel\'s cave (MC) pose a significant surgical challenge. Although several corridors to access this complex region have been described, the endoscopic transpterygoid approach (ETPA) and the endoscopic transorbital superior eyelid approach (ETOA) have emerged in recent years, as viable alternatives to traditional microsurgical transcranial approaches (MTA). To date, there is a limited literature on surgical series considering endoscopic-assisted approaches to the MC.
METHODS: We conducted a retrospective analysis of patients with primary MC tumors treated at our Institution between 2015 and 2022, specifically those managed via the ETPA assisted by intraoperative Endoscopic Diving Technique (EDT). Lesion resection extent was evaluated using pre- and post-intervention radiological images and surgical videos. Moreover, a literature review on ETPA was performed.
RESULTS: This series comprises 7 patients affected by 4 trigeminal schwannomas, 1 benign notochordal cell tumor, 1 dermoid cyst and 1 mesenchymal tumor. In 71 % of cases, trigeminal neuralgia was the presenting symptom. Post-operative clinical improvement was observed in all but one case. Notably, 85.7 % of patients achieved total or near-total resection (NTR), with the remaining case undergoing subtotal resection (STR). No significant intraoperative complications occurred, and no recurrences were observed during the mean follow-up period of 41 months.
CONCLUSIONS: In selected cases, the ETPA offers a direct and safe path to lesions located into the MC. This approach circumvents complications and constraints associated with ETOA or MTA. Moreover, the use of the EDT reduces manipulation of critical neurovascular structures, enhancing the efficacy of the ETPA.

Two cultivars of wild rocket (Diplotaxis tenuifolia), cv. Denver and Marte, were subjected to chemical determination of flavour-related constituents, sensory descriptive analysis, and measurement of liking by consumer test. Consumers evaluated rocket leaves both as a single ingredient and in a recipe formed by a roll of bresaola with also Grana Padano cheese. Sensory analyses showed that Marte was characterized by a more intense bitterness, hotness, and pungency, which corresponded to a higher total GSL content, mainly due to a higher level of dimeric 4-mercaptobutyl GSL. Five clusters of consumers were identified based on their liking scores. When tasting rocket leaves as a single ingredient, three clusters showed a higher liking for the milder cultivar, one cluster showed an opposite preference, while flavour attributes, such as bitterness and hotness, appeared as the main drivers of liking. Differences in liking were no longer found between the two cultivars when rocket leaves were evaluated in the recipe. Therefore, as rocket leaves are generally consumed as a part of a recipe with other ingredients instead of as a single ingredient, in the assessment of consumer preferences, it should not be neglected the influence of the way in which the product is consumed.

The temporomandibular joint (TMJ) consists of bone, cartilage, ligaments, and associated masticatory muscles and tendons that coordinate to enable mastication in mammals. The TMJ is innervated by the trigeminal nerve (CNV), containing axons of motor and somatosensory neurons. Somatosensation includes touch, temperature, proprioception, and pain that enables mammals to recognize and react to stimuli for survival. The somatosensory innervation of the TMJ remains poorly defined. Disorders of the TMJ (TMD) are of diverse etiology and presentation. Some known symptoms associated with TMD include facial, shoulder, or neck pain, jaw popping or clicking, headaches, toothaches, and tinnitus. Acute or chronic pain in TMD stems from the activation of somatosensory nociceptors. Treatment of TMD may involve over- the-counter and prescription medication, nonsurgical treatments, and surgical treatments. In many cases, treatment achieves only a temporary relief of symptoms including pain. We suggest that defining the sensory innervation of the temporomandibular joint and its associated tissues with a specific focus on the contribution of peripheral innervation to the development of chronic pain could provide insights into the origins of joint pain and facilitate the development of improved analgesics and treatments for TMD.