K2P channels underlie background K+ currents that act as brakes on neuronal excitability. In the somatosensory system, the K2P channels TASK-1 and TASK-3 play a relevant role in cold sensing, mechanosensitivity, and pain. Combining molecular docking and molecular dynamic simulations, patch-clamp recordings of recombinant channels, Ca2+-imaging and patch-clamp analysis in cultured primary somatosensory neurons from trigeminal and dorsal root ganglia, extracellular recording of the nerve endings of trigeminal neurons at the corneal surface, and behavioral analysis in mice models of acute, irritative, and neuropathic pain, we described and characterized the novel and rationally designed activator of TASK-1 and TASK-3 channels JG-C3-98. In HEK293 cells, JG-C3-98 showed a strong activation effect on TASK-1 and TASK-3, but not on TRAAK, TREK-1, TREK-2, and TRESK. In cultured primary somatosensory neurons, we have found that JG-C3-98 shifted the thermal threshold of cold thermoreceptor neurons to lower temperatures and reduced the maximal mechanically evoked responses in neurons responding to hypoosmotic stimulation. In ex vivo recordings of corneal cold-sensitive neurons, JG-C3-98 also shifted the thermal threshold of these nerve endings to lower temperatures. In a group of cultured dorsal root ganglia neurons, electrophysiological analysis suggests that JG-C3-98 reduces excitability and activates an outward current compatible with TASK-1/3 channels. Besides, intraplantar administration of a single dose of JG-C3-98 in the hind paw increases the threshold of the mechanically evoked pain sensitivity and reduces AITC-evoked nociceptive responses in mice. Importantly, in a model of neuropathic pain induced by chronic constriction of the sciatic nerve, we have found that cold allodynia resulting from this form of peripheral nerve damage is also reduced by intraplantar administration of a single dose of JG-C3-98 in the hind paw. Altogether, these results suggest that JG-C3-98 could be a new and potentially effective pharmacological tool for reducing cold and mechanical sensitivity across different somatosensory territories, both in physiological and pathophysiological conditions, and serve as a molecular scaffold for developing novel, more effective antinociceptive compounds that specifically act as TASK channels activators.

AbstractMorning Report is a time-honored tradition in which physicians-in-training present cases to their colleagues and clinical experts to collaboratively examine an interesting patient presentation. The Morning Report section seeks to carry on this tradition by presenting a patient's chief concern and story, inviting the reader to develop a differential diagnosis and discover the diagnosis alongside the authors of the case. This report examines the story of a 53-year-old woman who sought evaluation for pain in both ears, hearing loss, and facial weakness. Using questions, physical examination, and testing, an illness script for the presentation emerges. As the clinical course progresses, the differential is refined until a diagnosis is made.

Ocular neuropathic pain (ONP) can be defined as "pain" or "discomfort" projected to eye because of a lesion or disease or physiological dysfunction of the nervous system. The diagnosis of ONP is a clinical one; history, eye examination, the anesthetic challenge, and in vivo confocal microscopy providing supportive roles in helping to distinguish nociceptive, nociplastic, and neuropathic pain. Multimodal treatment involving local agents and interventions, along with systemic agents, is often required.

Hysteroscopic examination is commonly used to evaluate suspected intrauterine abnormalities, but procedure-related pain and anxiety may reduce tolerance and patient satisfaction. Auricular therapy is a nonpharmacologic intervention that may improve perioperative symptom control. This retrospective comparative study included 142 women who underwent hysteroscopic examination between September 2024 and December 2025. According to perioperative management, patients were divided into 4 groups: nonanesthesia without auricular therapy (group 1, n = 34), nonanesthesia with auricular therapy (group 2, n = 37), local anesthesia without auricular therapy (group 3, n = 32), and local anesthesia with auricular therapy (group 4, n = 39). Pain was assessed using the Numeric Rating Scale, and anxiety was evaluated using the Self-Rating Anxiety Scale. Intraoperative indicators, adverse events, and satisfaction were also recorded. Intraoperative and 30-minute postoperative Numeric Rating Scale scores differed significantly among groups (F = 5.220, P = .002; F = 11.019, P < .001), with group 2 showing the lowest pain scores. Among nonanesthetized patients, auricular therapy was associated with lower postoperative pain than no auricular therapy (mean difference 1.161, 95% confidence interval 0.710-1.611; P < .001). Postoperative 24-hour Self-Rating Anxiety Scale scores also differed significantly (F = 52.328, P < .001), with the highest score in group 1 and the lowest in group 2. No significant between-group differences were found in heart rate, blood pressure, or adverse event rates (all P > .05). All adverse events were mild and transient. Satisfaction was high in all groups, and the highest proportion of "very satisfied" patients was observed in group 2 (P = .013). Auricular therapy was associated with reduced perioperative pain, lower postoperative anxiety, and higher satisfaction during hysteroscopic examination, particularly in the nonanesthesia setting.

A 72-year-old Caucasian woman from the Southwestern United States presented with chronic right ear pain, hearing loss, and progressive hoarseness. Prior treatments, including balloon sinuplasty and tympanostomy tube placement, failed to resolve her symptoms. Imaging revealed right mastoid opacification, while flexible laryngoscopy demonstrated erythematous and polypoid changes of the right larynx. Pathology from biopsies of both the middle ear and larynx revealed spherules consistent with Coccidioides infection. She was treated with systemic fluconazole and underwent tympanomastoidectomy with mastoid debridement. The patient's postoperative course was uneventful, and she reported symptomatic improvement at follow-up. A multidisciplinary approach, including close coordination with infectious disease, guided long-term antifungal therapy. Coccidioidomycosis is a rare but important consideration in patients presenting with chronic head and neck symptoms, especially in endemic regions. This case highlights the potential for multifocal otolaryngologic involvement and underscores the need for a high index of suspicion in persistent or unexplained laryngeal and otologic disease. Diagnosis relies on biopsy and culture, and management typically requires both surgical and prolonged antifungal therapy. Multidisciplinary care is essential to optimize outcomes, particularly in cases involving bony structures or immunocompromised hosts.

Castleman disease constitutes a rare spectrum of conditions with rheumatologic, hematologic, and oncologic features. Orbital involvement is extremely rare with only several cases involving the lacrimal gland. This report describes Castleman disease in a 15-year-old patient who presented with progressive left eye bulging and intermittent periorbital pain. Neuroimaging demonstrated a well-defined, enhancing, homogeneous left lacrimal gland mass with decreased diffusivity, smooth bone remodeling, and anteromedial globe displacement, and no other systemic findings. The lesion was excised in toto and histopathology revealed features of hyaline vascular-type Castleman disease. This is the first reported case of Castleman disease in a pediatric patient with an isolated lacrimal gland lesion. It emphasizes the importance of considering Castleman disease among other lymphoproliferative diseases in the differential diagnosis for patients presenting with a well-circumscribed, homogeneous orbital mass associated with decreased diffusivity and bone remodeling.