Treatment Of Pain Research Articles

Botulinum toxin in the rehabilitation of painful syndromes: multiperspective literature analysis, lexical analysis and systematic review of randomized controlled trials.

Pain represents a common symptom of several diseases and is often associated with a reduction in rehabilitation outcomes and recovery. The effectiveness of pain alleviation by botulinum toxin has been recently demonstrated. We searched in PubMed the papers about this topic published in the last ten years, and we selected clinical trials, guidelines, meta-analyses, reviews, and systematic reviews. We used different approaches: multiperspective presentation, lexical evaluation, and systematic review. The systematic review was only performed for the randomized controlled trials. We predominantly found reviews and trials about the rehabilitation of stroke/brain injury and epicondylitis. The most common outcome measures were pain, function, and spasticity. Among the common words, pain was the most frequent and the terms were grouped into different families, especially concerning the outcomes. Rehabilitation showed a relatively low frequency. Finally, the systematic review showed moderate-low levels of bias which confirms the effectiveness of botulinum toxin for pain treatment. The current literature about botulinum toxin is wide and globally diffuse but with some limitations in study strategies and clearness in the formal presentation. The evidence justifies the use of botulinum toxin in treating pain in different diseases.

Acupuncture treatment for liver cancer pain: A meta-analysis.

Acupuncture treatment is a common intervention for the clinical relief of primary liver cancer (PLC) pain, but there is variability in its efficacy. This review systematically assessed the efficacy and safety of acupuncture treatment for PLC pain by meta-analysis. A total of 17 randomized controlled trial studies involving 1162 patients met the inclusion criteria. This study identified the acupuncture method, treatment duration, and patient age were the main factors affecting the efficacy of acupuncture treatment.

Genicular nerve radiofrequency ablation: a systematic review of application for perioperative pain control in total knee arthroplasty and as treatment for chronic pain in well-appearing total knee arthroplasty.

Total knee arthroplasty (TKA) is a successful treatment for end-stage osteoarthritis, yet some patients still experience postoperative pain. Genicular nerve radiofrequency ablation (GNRFA) has become a potential modality to address pain in TKA. This systematic review aims to critically analyze the applicability of GNRFAin perioperative pain control prior to TKA, as well as a treatment modality for chronic painful well-appearing TKA. PubMed, Medline, EMBASE, Google Scholar, Scopus, and COCHRANE databases, as well as theClinicalTrials.govregister, were reviewed. The search included randomized controlled trials and cohort studies. The sample population focused on two cohorts; those who underwent TKA and utilized intentional GNRFA as a perioperative pain control modality, and those utilizing the treatment modality for chronic pain in well-appearing TKA. GNRFA was the intervention studied, and postoperative outcomes were compared with the control group, which consisted of those not receiving GNRFA. Eight total publications were identified as relevant to this search. Among the pre-TKA studies, there was variability in results; these inconsistencies were attributed to a lack of standardization, especially with regard to type, timing, and targeted nerves with ablation. Likewise, while the results were improved among the population with chronic painful TKA receiving GNRFA, these inconsistencies still existed. Current evidence suggests GNRFA as a possible pre-TKA intervention to potentially minimize opioid consumption, patient-reported pain, length of stay, and increased range of motion and activity. However, the short-lived duration in the setting of chronically painful well-appearing TKA represents a major barrier that warrants further investigation. Limitations include small sample size, heterogeneity, lack of standardization of techniques among studies, and lack of direct comparison and meta-analysis. Further research should focus on the standardization of technique as well as analyzing various patient and health-system-related factors that correlate with sustained positive outcomes.

ALKBH5 modulates bone cancer pain in a rat model by suppressing NR2B expression.

Currently, the clinical treatment of bone cancer pain (BCP) is mainly related to its pathogenesis. The aim of the present study was to elucidate the potential role of N6-methyladenosine (m6A) in BCP in the spinal cord dorsal root ganglia (DRG) of BCP rats and its specific regulatory mechanism in N-methyl-d-aspartate receptor subunit 2B (NR2B). A rat model of BCP was constructed by tibial injection of Walker256 cells, and ALKBH5 and NR2B expression in the spinal cord DRG was detected. ALKBH5 was silenced or overexpressed in PC12 cells to verify the regulatory effect of ALKBH5 on NR2B. The specific mechanism underlying the interaction between ALKBH5 and NR2B was investigated using methylated RNA immunoprecipitation and dual-luciferase reporter gene assays. The results showed increased expression of m6A, decreased expression of ALKBH5, and increased expression of NR2B in the DRG of the BCP rat model. Overexpression of ALKBH5 inhibited NR2B expression, whereas interference with ALKBH5 caused an increase in NR2B expression. In NR2B, interference with ALKBH5 caused an increase in m6A modification, which caused an increase in NR2B. Taken together, ALKBH5 affected the expression of NR2B by influencing the stability of the m6A modification site of central NR2B, revealing that ALKBH5 is a therapeutic target for BCP.

HDAC inhibitors as a potential therapy for chemotherapy-induced neuropathic pain.

Cancer, a chronic disease characterized by uncontrolled cell development, kills millions of people globally. The WHO reported over 10 million cancer deaths in 2020. Anticancer medications destroy healthy and malignant cells. Cancer treatment induces neuropathy. Anticancer drugs cause harm to spinal cord, brain, and peripheral nerve somatosensory neurons, causing chemotherapy-induced neuropathic pain. The chemotherapy-induced mechanisms underlying neuropathic pain are not fully understood. However, neuroinflammation has been identified as one of the various pathways associated with the onset of chemotherapy-induced neuropathic pain. The neuroinflammatory processes may exhibit varying characteristics based on the specific type of anticancer treatment delivered. Neuroinflammatory characteristics have been observed in the spinal cord, where microglia and astrocytes have a significant impact on the development of chemotherapy-induced peripheral neuropathy. The patient's quality of life might be affected by sensory deprivation, loss of consciousness, paralysis, and severe disability. High cancer rates and ineffective treatments are associated with this disease. Recently, histone deacetylases have become a novel treatment target for chemotherapy-induced neuropathic pain. Chemotherapy-induced neuropathic pain may be treated with histone deacetylase inhibitors. Histone deacetylase inhibitors may be a promising therapeutic treatment for chemotherapy-induced neuropathic pain. Common chemotherapeutic drugs, mechanisms, therapeutic treatments for neuropathic pain, and histone deacetylase and its inhibitors in chemotherapy-induced neuropathic pain are covered in this paper. We propose that histone deacetylase inhibitors may treat several aspects of chemotherapy-induced neuropathic pain, and identifying these inhibitors as potentially unique treatments is crucial to the development of various chemotherapeutic combination treatments.

Efficacy and safety of topical capsaicin in the treatment of osteoarthritis pain: A systematic review and meta-analysis.

Osteoarthritis (OA) affects hundreds of millions of people worldwide. The objective was to critically appraise the efficacy and safety of topical capsaicin in reducing pain in OA. MEDLINE (PubMed) and Embase (Ebsco) were searched from inceptions until February 2023. The eligibility criteria included randomized controlled trials (RCTs), evaluating topical capsaicin in OA patients. Standard Cochrane methods were used to extract data and to appraise eligible studies. Eight double-blind RCTs involving 498 patients were included. Five trials (62.5%) were at an overall low risk of bias, and three (37.5%) were at a high risk of bias. Meta-analysis showed that, in various OA patients, compared with placebo, topical capsaicin (0.0125%-5%) may reduce pain severity measured with visual analog scale (standardized mean difference = -0.84, 95% confidence intervals [CIs] = -1.48 to -0.19, p = 0.01; eight studies). However, topical capsaicin may increase burning sensation at the application site (risk ratio = 5.56, 95% CI = 1.75-17.69, p = 0.004, numbers needed to harm = 3; five studies) when compared with placebo. Limitations include short study durations, small sample sizes, high heterogeneity, and overall low-to-very-low certainty of the evidence. Topical capsaicin may reduce OA pain at follow-ups of up to 3 months. Larger trials, potentially evaluating capsaicin in combination with phytopharmaceuticals having anti-inflammatory effects, with longer follow-ups might be needed to reduce the existing uncertainties. Topical capsaicin might be recommended for short-term management of pain in OA patients intolerant to nonsteroidal anti-inflammatory drugs.

Duloxetine and cognitive behavioral therapy with phone-based support for the treatment of chronic musculoskeletal pain: study protocol of the PRECICE randomized control trial.

Chronic musculoskeletal pain (CMP) is the most common, disabling, and costly of all pain conditions. While evidence exists for the efficacy of both duloxetine and web-based cognitive behavioral therapy (CBT) as monotherapy, there is a clear need to consider study of treatment components that may complement each other. In addition, given the reported association between patient's adherence and treatment outcomes, strategies are needed to enhance participant's motivation to adopt and maintain continued use of newly learned pain coping skills from CBT. Two hundred eighty participants will be recruited from the primary care clinics of a large academic health care system in North Carolina. Participants with CMP will be randomized to one of three treatment arms: (1) combination treatment (duloxetine + web-based self-guided CBT) with phone-based motivational interviewing (MI), (2) combination treatment without phone-based MI, and (3) duloxetine monotherapy. Participants will be in the study for 24 weeks and will be assessed at baseline, week 13, and week 25. The primary outcome is the Brief Pain Inventory (BPI)-Global Pain Severity score, which combines BPI pain severity and BPI pain interference. Secondary measures include between-group comparisons in mean BPI pain severity and BPI pain interference scores. Data collection and outcome assessment will be blinded to treatment group assignment. This randomized controlled trial (RCT) will determine if combination treatment with duloxetine and web-based CBT is superior to duloxetine monotherapy for the management of CMP. Furthermore, this RCT will determine the effectiveness of phone-based motivational interviewing in promoting the continued practice of pain coping skills, thereby enhancing treatment outcomes. NCT04395001 ClinicalTrials.gov. Registered on May 15, 2020.

Deciphering nociplastic pain: clinical features, risk factors and potential mechanisms.

Nociplastic pain is a mechanistic term used to describe pain that arises or is sustained by altered nociception, despite the absence of tissue damage. Although nociplastic pain has distinct pathophysiology from nociceptive and neuropathic pain, these pain mechanisms often coincide within individuals, which contributes to the intractability of chronic pain. Key symptoms of nociplastic pain include pain in multiple body regions, fatigue, sleep disturbances, cognitive dysfunction, depression and anxiety. Individuals with nociplastic pain are often diffusely tender - indicative of hyperalgesia and/or allodynia - and are often more sensitive than othersto non-painful sensory stimuli such as lights, odours and noises. This Review summarizes the risk factors, clinical presentation and treatment of nociplastic pain, and describes how alterations in brain function and structure, immune processing and peripheral factors might contribute to the nociplastic pain phenotype. This article concludes with a discussion of two proposed subtypes of nociplastic pain that reflect distinct neurobiological features and treatment responsivity.

Network Meta-analysis and Economic Evaluation of Neurostimulation Interventions for Chronic Non-surgical Refractory back Pain.

Different types of spinal cord stimulation (SCS) have now been evaluated for the management of chronic non-surgical refractory back pain (NSRBP). A direct comparison between the different types of SCS or between closed-loop SCS with conventional medical management (CMM) for patients with NSRBP has not been previously conducted, and therefore, their relative effectiveness and cost-effectiveness remain unknown. The aim of this study was to perform a systematic review, network meta-analysis (NMA) and economic evaluation of closed-loop SCS compared with fixed-output SCS and CMM for patients with NSRBP. Databases were searched to 8th September 2023. Randomised controlled trials of SCS for NSRBP were included. Results of studies were combined using fixed-effect NMA models. A cost-utility analysis was performed from the perspective of the UK National Health Service with results reported as incremental cost per quality-adjusted life-year (QALY). Closed-loop SCS resulted in statistically and clinically significant reductions in pain intensity (mean difference [MD] 32.72 [95% CrI 15.69-49.78]) and improvements in secondary outcomes compared to fixed-output SCS at 6-months follow-up. Compared to CMM, both closed-loop and fixed-output SCS result in statistically and clinically significant reductions in pain intensity (closed-loop SCS vs. CMM MD 101.58 [95% CrI 83.73-119.48]; fixed-output SCS versus CMM MD 68.86 [95% CrI 63.43-74.31]) and improvements in secondary outcomes. Cost-utility analysis shows that closed-loop SCS dominates fixed-output SCS and CMM, and fixed-output SCS also dominates CMM. Current evidence shows that closed-loop and fixed-output SCS provide more benefits and are cost-saving compared to CMM for patients with NSRBP.

Patient-Physician Sex Discordance and "Before Medically Advised" Discharge from Hospital: A Population-Based Retrospective Cohort Study.

Patient-physician sex discordance (when patient sex does not match physician sex) has been associated with reduced clinical rapport and adverse outcomes including post-operative mortality and unplanned hospital readmission. It remains unknown whether patient-physician sex discordance is associated with "before medically advised" hospital discharge (BMA discharge; commonly known as discharge "against medical advice"). To evaluate whether patient-physician sex discordance is associated with BMA discharge. Retrospective cohort study using 15years (2002-2017) of linked population-based administrative health data for all non-elective, non-obstetrical acute care hospitalizations from British Columbia, Canada. All individuals with eligible hospitalizations during study interval. Exposure: patient-physician sex discordance. BMA discharge (primary), 30-day hospital readmission or death (secondary). We identified 1,926,118 eligible index hospitalizations, 2.6% of which ended in BMA discharge. Among male patients, sex discordance was associated with BMA discharge (crude rate, 4.0% vs 2.9%; adjusted odds ratio [aOR] 1.08; 95%CI 1.03-1.14; p = 0.003). Among female patients, sex discordance was not associated with BMA discharge (crude rate, 2.0% vs 2.3%; aOR 1.02; 95%CI 0.96-1.08; p = 0.557). Compared to patient-physician sex discordance, younger patient age, prior substance use, and prior BMA discharge all had stronger associations with BMA discharge. Patient-physician sex discordance was associated with a small increase in BMA discharge among male patients. This finding may reflect communication gaps, differences in the care provided by male and female physicians, discriminatory attitudes among male patients, or residual confounding. Improved communication and better treatment of pain and opioid withdrawal may reduce BMA discharge.

Combined Ultrasound and Fluoroscopy versus Ultrasound versus Fluoroscopy-Guided Caudal Epidural Steroid Injection for the Treatment of Unilateral Lower Lumbar Radicular Pain: A Retrospective Comparative Study

Background and Objectives: This study aimed to evaluate the mid-term effectiveness and safety of a combined ultrasound (US) and fluoroscopy (FL)-guided approach in comparison to US-guided and FL-guided caudal epidural steroid injections (CESI) for treating unilateral lower lumbar radicular pain. Materials and Methods: A total of 154 patients who underwent CESI between 2018 and 2022 were included. Patients were categorized into three groups based on the guidance method: combined US and FL (n = 51), US-guided (n = 51), and FL-guided (n = 52). The study design was retrospective case-controlled, utilizing patient charts and standardized forms to assess clinical outcomes, adverse events, complications during the procedures. Results: In all groups, Oswestry Disability Index and Verbal Numeric Scale scores improved at 1, 3, and 6 months after the last injection, with no significant differences between groups (p < 0.05). The treatment success rate at all time points was also similar among the groups. Logistic regression analysis showed that injection method, cause, sex, age, number of injections, and pain duration did not independently predict treatment success. Blood was aspirated before injection in 2% (n = 1), 13.5% (n = 7), and 4% (n = 2) of patients in the combined US and FL groups, FL-guided groups, and US-guided groups, respectively. Intravascular contrast spread was detected in one patient in the combined method groups and seven in the FL-guided groups. Conclusions: When comparing pain reduction and functional improvement, there was no significant difference between the three methods. The combined method took less time compared to using FL alone. The combined approach also showed a lower occurrence of intravascular injection compared to using FL alone. Moreover, blood vessels at the injection site can be identified with an ultrasound using the combined method. Given these advantages, it might be advisable to prioritize the combined US- and FL-guided therapy when administering CESI for patients with unilateral lumbar radicular pain.

Bivalent and bitopic ligands of the opioid receptors: The prospects of a dual approach.

Opioid receptors belonging to the class A G-protein coupled receptors (GPCRs) are the targets of choice in the treatment of acute and chronic pain. However, their on-target side effects such as respiratory depression, tolerance and addiction have led to the advent of the 'opioid crisis'. In the search for safer analgesics, bivalent and more recently, bitopic ligands have emerged as valuable tool compounds to probe these receptors. The activity of bivalent and bitopic ligands rely greatly on the allosteric nature of the GPCRs. Bivalent ligands consist of two pharmacophores, each binding to the individual orthosteric binding site (OBS) of the monomers within a dimer. Bitopic or dualsteric ligands bridge the gap between the OBS and the spatially distinct, less conserved allosteric binding site (ABS) through the simultaneous occupation of these two sites. Bivalent and bitopic ligands stabilize distinct conformations of the receptors which ultimately translates into unique signalling and pharmacological profiles. Some of the interesting properties shown by these ligands include improved affinity and/or efficacy, subtype and/or functional selectivity and reduced side effects. This review aims at providing an overview of some of the bivalent and bitopic ligands of the opioid receptors and, their pharmacology in the hope of inspiring the design and discovery of the next generation of opioid analgesics.

Cryoablation Catheter Used in the Surgical Treatment of Atrial Fibrillation May Treat Chest Tube Pain: Engin Technique.

Postoperative pain after cardiac surgery plays an important role in the patient's recovery process. In particular, pain at the chest tube site can negatively affect the comfort and recovery of these patients. Effective pain control minimizes the risk of many complications. Oral and intravenous analgesics, epidural anesthesia, paravertebral block, and intercostal nerve blockade are used in chest tube pain control. We routinely use the surgical cryoablation method in the presence of atrial fibrillation in the preoperative period of cardiac surgery in our clinic. Here we aimed to describe our method of using the cryoablation catheter for intercostal nerve blockade.

Explorations of Agonist Selectivity for the α9* nAChR with Novel Substituted Carbamoyl/Amido/Heteroaryl Dialkylpiperazinium Salts and Their Therapeutic Implications in Pain and Inflammation.

There is an urgent need for nonopioid treatments for chronic and neuropathic pain to provide effective alternatives amid the escalating opioid crisis. This study introduces novel compounds targeting the α9 nicotinic acetylcholine receptor (nAChR) subunit, which is crucial for pain regulation, inflammation, and inner ear functions. Specifically, it identifies novel substituted carbamoyl/amido/heteroaryl dialkylpiperazinium iodides as potent agonists selective for human α9 and α9α10 over α7 nAChRs, particularly compounds 3f, 3h, and 3j. Compound 3h (GAT2711) demonstrated a 230 nM potency as a full agonist at α9 nAChRs, being 340-fold selective over α7. Compound 3c was 10-fold selective for α9α10 over α9 nAChR. Compounds 2, 3f, and 3h inhibited ATP-induced interleukin-1β release in THP-1 cells. The analgesic activity of 3h was fully retained in α7 knockout mice, suggesting that analgesic effects were potentially mediated through α9* nAChRs. Our findings provide a blueprint for developing α9*-specific therapeutics for pain.

The Contribution of Psychological Symptoms to Cognitive Difficulties in Youth With Postural Orthostatic Tachycardia Syndrome and Chronic Pain.

Subjectively experienced cognitive difficulties are common in youth with postural orthostatic tachycardia syndrome. The pathophysiological and psychological contributions of these cognitive impairments remain unclear. Participants were 96 adolescents and young adults diagnosed with postural orthostatic tachycardia syndrome and admitted to an intensive pain treatment program. Participants completed cognitive assessment and measures of postural orthostatic tachycardia syndrome symptoms, pain intensity, pain catastrophizing, anxiety, depression, and functional disability. Self-reported autonomic symptom intensity, but not severity of heart rate change, was associated with cognitive performance. Symptoms of depression were associated with decreases in most measures of cognitive functioning. Pain intensity, pain catastrophizing, and depression but not cognitive scores and physiological measures, were significant predictors of disability. Depression appears to be a significant contributor to the cognitive difficulties in youth with postural orthostatic tachycardia syndrome. These findings highlight the importance of assessing and treating affective symptoms in this population along with medical and lifestyle approaches to treating postural orthostatic tachycardia syndrome symptoms.

Multidisciplinary strategies to treat painful mononeuropathies in the upper extremity: from lab to bedside.

Neuropathic pain in the upper extremity is a serious problem, commonly involving relatively young patients. The pain causes loss of function and productivity, changes a patient's lifestyle and can progress into a chronic pain syndrome with secondary psychosocial co-morbidities. Treating patients with a painful mononeuropathy remains challenging, with a monodisciplinary approach often having limited treatment efficacy. This narrative review discusses how to deal with this challenge in the treatment of patients with peripheral nerve injury pain, addressing the four important pillars: (1) diagnosing a painful mononeuropathy; (2) clinical pain phenotyping; (3) personalized pain treatment; and (4) using a multidisciplinary team approach.

Transcriptomic signature, bioactivity and safety of a non-hepatotoxic analgesic generating AM404 in the midbrain PAG region

Safe and effective pain management is a critical healthcare and societal need. The potential for acute liver injury from paracetamol (ApAP) overdose; nephrotoxicity and gastrointestinal damage from chronic non-steroidal anti-inflammatory drug (NSAID) use; and opioids’ addiction are unresolved challenges. We developed SRP-001, a non-opioid and non-hepatotoxic small molecule that, unlike ApAP, does not produce the hepatotoxic metabolite N-acetyl-p-benzoquinone-imine (NAPQI) and preserves hepatic tight junction integrity at high doses. CD-1 mice exposed to SRP-001 showed no mortality, unlike a 70% mortality observed with increasing equimolar doses of ApAP within 72 h. SRP-001 and ApAP have comparable antinociceptive effects, including the complete Freund’s adjuvant-induced inflammatory von Frey model. Both induce analgesia via N-arachidonoylphenolamine (AM404) formation in the midbrain periaqueductal grey (PAG) nociception region, with SRP-001 generating higher amounts of AM404 than ApAP. Single-cell transcriptomics of PAG uncovered that SRP-001 and ApAP also share modulation of pain-related gene expression and cell signaling pathways/networks, including endocannabinoid signaling, genes pertaining to mechanical nociception, and fatty acid amide hydrolase (FAAH). Both regulate the expression of key genes encoding FAAH, 2-arachidonoylglycerol (2-AG), cannabinoid receptor 1 (CNR1), CNR2, transient receptor potential vanilloid type 4 (TRPV4), and voltage-gated Ca2+ channel. Phase 1 trial (NCT05484414) (02/08/2022) demonstrates SRP-001’s safety, tolerability, and favorable pharmacokinetics, including a half-life from 4.9 to 9.8 h. Given its non-hepatotoxicity and clinically validated analgesic mechanisms, SRP-001 offers a promising alternative to ApAP, NSAIDs, and opioids for safer pain treatment.

Unveiling the Placebo Effect: How Belief Shapes Relief in Low Back Pain

Low back pain is a complex condition that is influenced by biological, psychological and social factors and poses considerable challenges for effective treatment. The biopsychosocial model of pain emphasizes the importance of incorporating various factors into treatment strategies. In this context, the placebo effect emerges as a remarkable phenomenon that offers insights into the interplay of persuasion and relief in the treatment of low back pain. This paper explores the multifaceted nature of low back pain and highlights the role of the placebo effect in shaping treatment outcomes. It looks at recent research highlighting the influence of patient-practitioner interactions, contextual factors and neurobiological mechanisms on placebo responses. It also discusses how placebo interventions, ranging from inert substances to sham surgery, have shown significant efficacy in relieving low back pain symptoms. Neuroimaging studies have provided valuable insights into the neural mechanisms underlying the placebo effect, enabling the development of targeted interventions. In addition, ethical considerations related to the use of placebos, including transparency, informed consent and harm minimization, are addressed to ensure ethical practice. Healthcare providers are encouraged to harness the placebo effect through evidence-based interventions and patient-centered care. Through the use of positive communication, empathy and complementary therapies, clinicians can optimize treatment outcomes and improve the overall well-being of patients. Looking to the future, interdisciplinary collaboration and advances in neuroscience promise to further unlock the therapeutic potential of the placebo effect in the treatment of low back pain. By combining scientific rigor and compassionate care, healthcare providers can navigate the complexities of placebo use in an ethical and effective manner, ultimately improving outcomes for patients with low back pain and other chronic conditions.

True lateral imaging during lumbar medial branch radiofrequency neurotomy: Interobserver reliability

BackgroundTrue lateral imaging (TLI), obtained by superimposing bilateral lumbar spine structures and aligning superior endplate cortical bone, requires deliberate rotational adjustments of the laterally positioned fluoroscope in both the axial and longitudinal planes. True lateral segmental imaging is necessary to depict true and accurate radiofrequency (RF) cannula positioning relative to bony anatomy during lumbar medial branch radiofrequency neurotomy (LMBRFN). ObjectiveTo determine the interobserver reliability of TLI during LMBRFN. MethodsThis was a retrospective review of a prospectively generated collection of lateral fluoroscopic images to determine the interobserver reliability of TLI during LMBRFN. Lateral fluoroscopic images were prospectively collected from 34 consecutive L4-5 and L5-S1 LMBRFN procedures during routine clinical practice. Employing International Pain and Spine Intervention Society (IPSIS) LMBRFN and TLI techniques, an RF cannula was positioned parallel to the L3 and L4 medial branches and the L5 dorsal rami. During the normal course of TLI, untrue and final true lateral segmental images were obtained and saved. An original data set of 100 pairs of true and untrue lateral images was reviewed to verify true laterality using established criteria; disagreement was resolved by consensus or discarding ambiguous cases. To measure interobserver reliability (Cohen's Kappa), two blinded expert reviewers independently reviewed the image set, identifying the true lateral image and the plane requiring correction. ResultsThe observers agreed upon 98/98 true lateral RF-segment images (Kappa score 1.0 [1.00,1.00]). The observers agreed upon 86/98 maneuvers to correct the untrue RF-segment image. The Kappa score for determining the most appropriate corrective maneuver was 0.76 (0.63,0.89), showing substantial interobserver agreement. ConclusionsThe true lateral image of the targeted RF segment during LMBRFN was reliably determined with perfect interobserver agreement. Interobserver agreement was substantial regarding the maneuver to achieve TLI.

Propellant Free Pressurized Spray System of Etodolac to Manage Acute Pain Conditions: In Vitro and In Vivo Evaluation.

This study aimed to develop a propellant-free topical spray formulation of Etodolac (BCS-II), a potent NSAID, which could be beneficial in the medical field for the effective treatment of pain and inflammation conditions. The developed novel propellant-free spray formulation is user-friendly, cost-effective, propellant-free, eco-friendly, enhances the penetration of Etodolac through the skin, and has a quick onset of action.Various formulations were developed by adjusting the concentrations of different components, including lecithin, buffering agents, film-forming agents, plasticizers, and permeation enhancers. The prepared propellant-free spray formulations were then extensively characterized and evaluated through various in vitro, ex vivo, and in vivo parameters. The optimized formulation exhibits an average shot weight of 0.24 ± 0.30ml and an average drug content or content uniformity of 87.3 ± 1.01% per spray. Additionally, the optimized formulation exhibits an evaporation time of 3 ± 0.24min. The skin permeation study demonstrated that the permeability coefficients of the optimized spray formulation were 21.42cm/h for rat skin, 13.64cm/h for mice skin, and 18.97cm/h for the Strat-M membrane. When assessing its potential for drug deposition using rat skin, mice skin, and the Strat-M membrane, the enhancement ratios for the optimized formulation were 1.88, 2.46, and 1.92, respectively against pure drug solution. The findings from our study suggest that the propellant-free Etodolac spray is a reliable and safe topical formulation. It demonstrates enhanced skin deposition, and improved effectiveness, and is free from any skin irritation concerns.