Nicotine-induced ER Stress and ASM Cell Proliferation is Mediated by α7nAChR and Chaperones-RIC-3 and TMEM35.

Nicotine exposure in the context of smoking or vaping worsens airway function. Although commonly thought to exert effects through the peripheral nervous system, we previously showed airway smooth muscle (ASM) expresses nicotinic acetylcholine receptors (nAChRs), particularly alpha7 subtype (α7nAChR) with functional effects on contractility and metabolism. However, the mechanisms of nAChR regulation and downstream effects in ASM are not fully understood. Using human ASM cells from non-asthmatics vs. mild-moderate asthmatics, we tested the hypothesis that nAChR-specific ER chaperones RIC-3 and TMEM35 promote cell surface localization of α7nAChR with downstream influence on its functionality: effects exacerbated by inflammation. We found that mild-moderate asthma and exposure to pro-inflammatory 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, Ca2+ regulation and ASM cell proliferation. Overall, our data highlights the importance α7nAChR chaperones in mediating and modulating nicotine effects in ASM towards airway contractility and remodeling.

Infrapatellar Branch of the Saphenous Nerve: Therapeutic Approaches to Chronic Knee Pain.

PURPOSE OF REVIEW: The infrapatellar branch of the saphenous nerve (IPS) is an under-investigated nerve that can be a source of chronic knee pain. This literature review aims to deliver an up-to-date review of chronic pain transmitted via the IPS along with therapeutic approaches available for pain refractory to conservative measures. RECENT FINDINGS: Knee pain transmitted via the IPS can arise from several etiologies. Damage to the IPS is often iatrogenic and develops following total knee arthroplasty, anterior cruciate ligament reconstruction, and other knee surgical procedures. Other causes of IPS-derived pain include entrapment of the nerve, neuromas, Schwannomas, and pain from knee osteoarthritis transmitted through the IPS.This article investigated therapeutic approaches to pain derived from the IPS. Common approaches included radiofrequency ablation, neuroma excisions, Schwannoma excision, nerve blocks, surgical exploration, surgical release of an entrapped nerve, cryoablation, and peripheral nerve stimulation. Pain scores, duration of pain relief, adverse events, and secondary outcomes were all included in this review. A subset of the patient population experiences chronic pain deriving from the IPS that is refractory to conservative treatment measures. This review aims to evaluate the etiologies and therapeutic approaches for chronic pain arising from the IPS refractory to conservative treatments.

Outcomes of cooled radiofrequency ablation of cervical nerves for the treatment of chronic pain.

BACKGROUND: Chronic pain, defined as pain persisting for more than 3-6 months, has a mean one-year prevalence in the United States of 25.8% and is one of the most frequent reasons adults seek medical care. Treatment options include physical therapy, analgesics, anticonvulsants, exercise, and muscle relaxants. Even with conventional treatment modalities, in a subset of patients, pain may persist. Cooled radiofrequency ablation (c-RFA), a minimally invasive therapy, employs thermal energy generated by electrical currents to disrupt the transmission of pain stimuli along nociceptive pathways. This leads to an attenuation of pain impulses, primarily through nerve tissue necrosis. The potential of c-RFA to alleviate chronic pain for patients who struggle to find relief elsewhere accentuates the importance of rigorously investigating its outcomes. This study investigates whether patients receiving c-RFA for relief of chronic neck pain caused by cervical facet joint arthropathy experience a reduction in pain scores, the length of this reduction in pain scores, and the magnitude of this reduction in pain. METHODS: This study was a retrospective analysis of data extracted from UW-Health Electronic Medical Health records (EMR), encompassing cervical c-RFA procedures performed from 2015 through 2022. Patient data were obtained, including diagnosis, pre-operative pain score, post-operative pain score, duration of relief, patient age, sex, and BMI. A two-tailed paired t-test was used to statistically analyze the pre-operative and post-operative pain scores, in which a p-value ≤0.05 was considered significant. RESULTS: A total of 450 cervical c-RFA procedures were reviewed, 152 were excluded due to absent pre- or post-op pain scores. 298 were included in the analysis, comprising 203 unique patients: 129 females and 74 males with an average age of 56.03 ± 12.76 and a BMI of 28.76 ± 6.05. Improvement of pain symptoms was reported in 85.23% (n = 263), 6% (n = 19) reported complete pain remission, 8.72% (n = 26) reported no change, and 3.02% (n = 9) reported worsening symptoms. Patients reported an average pre-operative pain score of 6.15 (M = 6.15, SD = 1.55) and an average post-operative pain score of 3.64 (M = 3.64, SD = 2.09) this achieved significance (p < 0.0001). Of the 85.23% (n = 263) charts that noted improvement, there is an average of 48.04% ± 26.53 reduction from their pre-operative pain scores. The average duration of relief lasted 6.67 ± 4.84 months. CONCLUSION: This study supports the potential efficacy of c-RFA as a minimally invasive treatment for chronic neck pain secondary to cervical facet joint arthropathy refractory to conventional treatment measures, demonstrating significant relief for a substantial length of time. Due to chronic pain's detrimental effect on one's quality of life, finding effective treatment options is essential, especially for those refractory to conventional treatments.

Efficacy of Cooled-Radiofrequency Ablation of the Genicular Nerve as Treatment for Chronic Knee Pain: A Retrospective Study.

INTRODUCTION: Chronic pain is one of the leading causes of reduced quality of life in the USA, with knee pain commonly reported. Multiple therapeutic modalities are traditionally utilized for pain management; however, some patients may have pain refractory to these techniques. Cooled radiofrequency ablation (c-RFA) of the geniculate nerve is a growing and promising therapy offering a potentially long-term solution to chronic knee pain. METHODS: This study assessed the efficacy, average duration of relief, and potential adverse events using a retrospective chart review of 406 procedures. A two-tailed paired t test was used to assess the statistical significance between pre-RFA vs. post-RFA visual analog scale (VAS) pain scores self-reported by patients. An analysis of variance (ANOVA) test was used to evaluate for statistical differences in pre-RFA pain scores and post-RFA pain scores among the categories of age, sex, body mass index (BMI), and diagnosis group. RESULTS: The mean percent in pain improvement calculated was 65.5% with an average duration of relief of 7.20 months. The average pre-RFA pain score on the VAS was 6.26 out of 10 and 2.59 out of 10 post-RFA. The ANOVA post-RFA pain scores demonstrated statistically significant differences among the categories of age and sex. A total of 54 adverse events were reported, including worsening pain, numbness, paresthesia, and knee swelling. CONCLUSION: The study demonstrated that c-RFA can potentially be utilized as an alternative safe therapy for chronic knee pain, providing pain relief with a relatively prolonged duration. Inherent challenges of retrospective studies remain a part of the limitations of this study.