Nicotine exposure in the context of smoking or vaping worsens airway function. Although nicotinic acetylcholine receptors (nAChRs) are commonly thought to exert effects through the peripheral nervous system, we previously showed that airway smooth muscle (ASM) expresses them, particularly α7 subtype nAChR (α7nAChR), with functional effects on contractility and metabolism. However, the mechanisms of nAChR regulation and downstream effects in ASM are not fully understood. Using ASM cells from people without asthma versus people with mild to moderate asthma, we tested the hypothesis that nAChR-specific endoplasmic reticulum (ER) chaperones, resistance to inhibitors of cholinesterase 3 (RIC-3) and transmembrane protein 35A (TMEM35A) promote cell surface localization of α7nAChR with downstream influence on its functionality: effects exacerbated by inflammation. We found that mild to moderate asthma and exposure to proinflammatory cytokines relevant to asthma promote chaperone and α7nAChR expression in ASM. Downstream, ER stress was linked to nicotine/α7nAChR signaling, where RIC-3 and TMEM35 regulate nicotine-induced ER stress, intracellular Ca2+ regulation, and ASM cell proliferation. Overall, our data highlight the importance α7nAChR chaperones in mediating and modulating nicotine effects in ASM toward airway contractility and remodeling.

Background/Objectives: Spinal cord injury (SCI) presents significant challenges in restoring motor function, with limited therapeutic options available. Recent advancements in neuromodulation technologies, such as brain-spine interface (BSI), epidural electrical stimulation (EES), and deep brain stimulation (DBS), offer promising solutions. This review article explores the integration of these approaches, focusing on their potential to restore function in SCI patients. Findings: DBS has shown efficacy in SCI treatment with several stimulation sites identified, including the nucleus raphe magnus (NRM) and periaqueductal gray (PAG). However, transitioning from animal to human studies highlights challenges, including the technical risks of targeting the NRM in humans instead of rodent models. Additionally, several other regions have shown potential for motor rehabilitation, including the midbrain locomotor region (MLR) pathways, cuneiform nucleus (CnF), pedunculopontine nucleus (PPN), and lateral hypothalamic. DBS with EES further supports motor recovery in SCI; however, this approach requires high-DBS amplitude, serotonergic pharmacotherapy, and cortical activity decoding to attenuate stress-associated locomotion. BSI combined with EES has recently emerged as a promising novel therapy. Although human studies are limited, animal models have provided evidence supporting its potential. Despite these advancements, the effectiveness of DBS and combined systems remains limited in cases of complete central denervation. Conclusions: The integration and combination of DBS, BSI, and EES represent a transformational approach to treating and restoring function in patients with SCI. While further research is needed to optimize these strategies, these advancements hold immense potential for improving the quality of life in SCI patients and advancing the field of neuromodulation.

Background: Chronic thoracic pain is commonly caused by thoracic facet dysfunction, intercostal neuralgia, surgery, or thoracic pain secondary to cancer and is present in approximately 15% of the population. Conventional treatments, including pharmacotherapy and transcutaneous electrical nerve stimulation, are often ineffective and are often associated with poorly tolerated adverse effects. Cooled radiofrequency ablation (c-RFA) is a minimally invasive procedure that uses radiofrequency energy delivered through a probe to lesion the targeted nerve and provide significant and lasting relief. Methods: This study was a retrospective analysis of data extracted from UW-Health Electronic Medical Health records from October 2015 through June 2024. Patient data were collected, including diagnosis, pre-operative pain score, post-operative pain score, duration of relief, age, sex, and BMI. A two-tailed paired t-test was used to analyze the pre-operative and post-operative pain scores. A p-value < 0.05 was considered significant. Results: A total of 111 thoracic c-RFA procedures were reviewed; 43 were excluded due to absent pre-operative or post-operative pain scores in medical records. A total of 68 procedures were included in the analysis, comprising 55 patients: 25 females and 30 males with an average age of 51.31 ± 18.22 years and a BMI of 29.79 ± 6.48 kg/m². Improvement in pain scores was reported in 77.94% (n = 53), 16.18% (n = 11) reported no change, and 5.88% (n = 4) reported worsening pain. Patients reported an average pre-operative pain score of 5.98 (M = 5.98, SD = 1.91) and an average post-operative pain score of 3.06 (M = 3.06, SD = 2.52); this achieved significance (p < 0.0001). Of the 77.94% (n = 53) charts that noted improvement, there is an average of 62.83 ± 28.48% reduction from their pre-operative pain scores. The average duration of relief lasted 11.85 ± 13.42 months. Conclusions: This study supports the efficacy and safety of c-RFA as a minimally invasive therapy for chronic thoracic pain refractory to conservative measures.

Meralgia paresthetica (MP) is neuropathic pain in the anterolateral thigh, most often caused by compression or injury to the lateral femoral cutaneous nerve (LFCN). Conservative treatments include weight loss, avoidance of compressive clothing, medical management with anti-inflammatory and neuropathic agents, and corticosteroid injections. For patients with MP refractory to these measures, radiofrequency ablation (RFA) is a minimally invasive option that may provide pain relief. This article introduces a novel ultrasound-guided continuous RFA technique designed to create a controlled thermal lesion of the LFCN, along with preliminary clinical outcomes. Pronounced anatomic variation of the LFCN at the anterior superior iliac spine makes real-time imaging essential for procedural accuracy, with ultrasound offering consistent nerve visualization and precise needle placement. Continuous RFA has demonstrated substantial and durable reductions in VAS scores, whereas pulsed RFA provides shorter-term relief with a favorable safety profile, and cooled RFA produces broader lesions that may help address anatomical variability, although supporting evidence is limited. Overall, RFA can be an effective treatment for MP refractory to conservative therapy, with optimal results dependent on detailed anatomical knowledge and accurate image guidance, particularly when using the novel continuous RFA approach described in this study.

Background: Chronic pain poses a significant challenge to the general population, especially in older adults. As a result, there is a growing emphasis on developing novel treatment options and expanding the use of emerging technologies. Objective: This comprehensive review aims to guide practitioners in chronic pain management by extending the current application of vagus nerve stimulation (VNS). The review examined peer-reviewed studies, including multicenter cohort studies and clinical trials, published within the past 25 years. VNS has shown the most promising results in pain reduction for headache and migraine, with less relief in inflammatory and neuropathic pain as compared to current first-line treatment options. Conclusion: Overall, this review seeks to compile and critically analyze the effect and efficacy of VNS on different forms of chronic pain using the most current studies and research applicable.

Introduction Headaches are among the most prevalent and disabling sources of pain, affecting nearly half of adults worldwide. Many patients experience debilitating headaches refractory to conservative treatments, including pharmacotherapy, steroid injections, or other interventional therapies. Radiofrequency ablation (RFA) is a minimally invasive technique that uses controlled thermal energy to create targeted tissue necrosis, disrupting the nociceptive signaling within targeted sensory nerves, and is a promising therapy for patients with chronic headaches refractory to conservative treatments. The objective of this study is to evaluate the clinical efficacy of thermal RFA for chronic headache management by examining changes in pain scores and the duration and degree of symptom relief. Methods This retrospective chart review of this study investigates patients who received thermal RFA of the occipital, supraorbital, supratrochlear, infraorbital, infratrochlear, and/or anterior ethmoid nerves between 2015 and 2025. Preoperative and postoperative pain scores were assessed using the Visual Analogue Scale (VAS). Additionally, the duration of relief and any adverse events associated with the procedures were recorded. Paired t-tests were performed between preoperative and postoperative VAS pain scores to determine statistical significance, with a p-value of ≤ 0.05 denoting significance. Results In total, 940 procedures were reviewed; 108 were excluded, and 832 procedures from 464 patients were included. The 464 patients comprised 369 female and 95 male patients, with a mean age of 44.83 ± 15.99 years and body mass index (BMI) of 29.65 ± 7.44 kg/m². Average preoperative and postoperative VAS scores were 5.34 ± 2.01 and 3.04 ± 2.33, respectively, representing a statistically significant reduction (p < 0.001). Quantitative or qualitative improvement was reported in 68.63% of procedures, and 13.10% noted complete remission for a total of 81.73% experiencing pain relief, whereas 18.27% saw no change. Among effective cases, the mean improvement was 60.20 ± 28.54%, lasting an average of 7.47 ± 9.78 months. A total of 12 adverse events were reported. Conclusions These findings suggest that thermal RFA of pericranial nerves can offer meaningful, lasting relief for patients with neuralgic headaches that resist traditional treatments. As a minimally invasive option with limited side effects, RFA may reduce the need for ongoing pharmacologic management and improve the quality of life for chronic headache sufferers.