Does Liposomal Bupivacaine Reduce Postoperative Pain Following Third Molar Extractions? A Double-Blinded Randomized Controlled Trial

BackgroundLiposomal bupivacaine (LB) is a long-lasting local anesthetic providing analgesia for several days. The current literature examining the efficacy of LB in pain management following third molar extractions remains unclear.PurposeThe purpose of this study was to compare postoperative pain management between LB and standard bupivacaine (SB) in mandibular third molar extractions.Study designA double-blinded randomized controlled trial of subjects undergoing bilateral mandibular third molar extractions at our institution from 2022 to 2024 was conducted using a split-mouth study design. Subjects were excluded if they received additional mandibular teeth extractions, were unable to complete the questionnaire, or had medical contraindications.Predictor variableThe predictor variable was postsurgical local anesthetic agent, and the sides of mouth were randomly assigned to LB or SB.Main outcome variable(s)Primary outcome was postoperative pain on a 10-point numerical rating scale (NRS), and the mean cumulative pain rating via area under the curve (AUC) analysis. Secondary outcomes were adverse events and ibuprofen or acetaminophen consumption.CovariatesDemographics, procedure time, preoperative and perioperative local anesthetics used, and procedural difficulty coded as nonsurgical or surgical were collected.AnalysesWe used mixed-effects models to compare the NRS scores during each time period and paired t-tests to compare AUC values. Statistical tests included 95% CIs with alpha = 0.05.ResultsThe study sample included 72 subjects (mean age 25.8, SD: 9). Pain was lower in the LB versus SB group on surgery day (NRS difference -0.75; P = .002) until the morning of postoperative day 2 (-0.68, P = .003). When limiting the analysis to bilateral surgical extractions, it was statistically significant until the morning of postoperative day 3 (-0.61, P = .02). AUC analysis showed cumulative pain reduction for the LB group in comparison to the SB group through all 4 postoperative days for the overall cohort (average AUC0-96 difference 93.5, P = .005), with a similar effect for bilateral surgical extractions (101.88, P = .006).ConclusionLB modestly reduces pain following third molar extractions, with this difference more pronounced following surgical extractions. This suggests that LB may be more beneficial in complex extractions and greater pain-inducing surgeries

Durability of Supplemental Nucleus Pulposus Allograft in Patients with Lumbar Discogenic Pain

Shrif Costandi,1 Douglas P Beall,2 Timothy T Davis,3 Kasra Amirdelfan,4 Ramana K Naidu,5 Michael J DePalma,6 Edward S Yoon,7 Jacob W Fleming,8 Jon E Block,9 Nagy Mekhail1 1Pain Management, Cleveland Clinic, Cleveland, OH, USA; 2Comprehensive Specialty Care, Edmond, OK, USA; 3Source Healthcare, Santa Monica, CA, USA; 4Boomerang Healthcare, Inc., Walnut Creek, CA, USA; 5MarinHealth Spine Institute, Larkspur, CA, USA; 6Virginia iSpine Physicians, Richmond, VA, USA; 7Interventional Radiology, Hospital for Special Surgery, New York, NY, USA; 8Vascular and Interventional Specialists, Dallas, TX, USA; 9Private Practice, San Francisco, CA, USACorrespondence: Jon E Block, Private Practice, 2210 Jackson Street, Ste. 401, San Francisco, CA, 94115, USA, Tel +1 415-775-7947, Email [email protected]: The objective of this study was to determine the degree of improvement in lumbar discogenic pain severity and associated back impairment in patients with chronic axial low back pain treated with intradiscally delivered allogeneic nucleus pulposus (NP) at up to two vertebral levels (L1-S1).Methods: Prospective, single-arm clinical study conducted at 6 sites in the US involving 28 participants with discogenic pain (mean age: 44 ± 13 yrs) and modified Pfirrmann grade 3– 7 on magnetic resonance imaging. This report includes the final participant follow up at 24 months post procedure. Back pain severity was evaluated using an 11-point numeric rating scale (NRS) and back function using the Oswestry Disability Index (ODI). Minimal clinically important difference (MCID) and substantial clinical benefit (SCB) were set at ≥ 30% and ≥ 50% over baseline, respectively. The patient acceptable symptom state (PASS) threshold for pain severity was ≤ 3.Results: The average improvement in back pain severity from 7.1 ± 1.6 at baseline to 3.6 ± 2.9 at 24 months was 43% (p< 0.001). Approximately 64% (14 of 22) of participants achieved both the MCID and SCB in back pain at 24 months, while nearly 55% (12 of 22) reported a 24-month back pain severity score of ≤ 3. The corresponding average decrease in ODI values was 53% (p< 0.001) with 73% (16 of 22) of participants achieving the MCID. At baseline approximately 82% (23 of 28) of participants reported severe or crippled back impairment compared to 18% (4 of 22) at 24 months (p< 0.001). There was no association between modified Pfirrmann grade, number of levels treated or Modic changes and any outcome (range: p=0.12 to 0.43).Conclusion: This study provides evidence of clinically significant pain relief and functional improvement through 24 months of follow up after a single allogeneic NP supplementation procedure in patients with lumbar discogenic pain.Keywords: nucleus pulposus, allograft, discogenic, back pain, intradiscal, degenerative disc diseas

The American Society of Pain and Neuroscience (ASPN) Guidelines and Consensus on the Definition, Current Evidence, Clinical Use and Future Applications for Physiologic Closed-Loop Controlled Neuromodulation in Chronic Pain: A NEURON Group Project.

INTRODUCTION: Neuromodulation has been a staple of treatment for moderate-to-severe chronic refractory pain since the introduction of the first spinal cord stimulator by Norman Shealy in 1967. Appreciating the dynamic nature of electrical modulation of the nervous system from the epidural space, the goal has been consistent, reliable, and therapeutic neural activation of the spinal cord. This has proven to be extremely difficult. Recently, the Food and Drug Administration (FDA) released a guidance on physiologic closed loop controlled (PCLC) devices, highlighting the potential for these therapies to deliver accurate, consistent, real-time therapy, enhancing medical care and reducing variability. Because of the growing neuromodulation market focus on PCLC strategies, the American Society of Pain and Neuroscience (ASPN) sought to develop guidance on safety and efficacy, along with a taxonomy surrounding PCLC systems (PCLCSs) and to develop an evidence-based best practice review. METHODS: A librarian-assisted literature search was performed to identify manuscripts relevant to the topic of PCLC stimulation for management of chronic pain. Initial literature search was performed utilizing MEDLINE, EMBASE, Cochrane database, BioMed Central, and Web of Science. Included manuscripts encompassed meta-analyses, systematic reviews, randomized controlled trials (RCTs), prospective or retrospective studies with follow-up to 12 months, limited to the English language. MESH terms utilized included closed-loop, physiologic closed loop controlled, spinal cord stimulation, closed loop feedback, feedback controlled, neuromodulation, pain, persistent pain, neuropathic pain, and chronic pain. The modified USPSTF evidence and recommendation grading strategy previously utilized was again employed. RESULTS: Four studies were identified for review, 2 prospective, one retrospective, and one randomized controlled study with at least 12-month follow-up. CONCLUSION: PCLC neuromodulation is an innovation that requires a responsible introduction. As commercial access grows, there is a responsibility that requires consistency with definition, evidence generation, focused on safety and efficacy

Brain data:Scanning, scraping and sculpting the plastic learning brain through neurotechnology

Neurotechnology is an advancing field of research and development with significant implications for education. As 'postdigital' hybrids of biological and informational codes, novel neurotechnologies combine neuroscience insights into the human brain with advanced technical development in brain imaging, brain-computer interfaces, neurofeedback platforms, brain stimulation and other neuroenhancement applications. Merging neurobiological knowledge about human life with computational technologies, neurotechnology exemplifies how postdigital science will play a significant role in societies and education in decades to come. As neurotechnology developments are being extended to education, they present potential for businesses and governments to enact new techniques of 'neurogovernance' by 'scanning' the brain, 'scraping' it for data and then 'sculpting' the brain toward particular capacities. The aim of this article is to critically review neurotechnology developments and implications for education. It examines the purposes to which neurotechnology development is being put in education, interrogating the commercial and governmental objectives associated with it and the neuroscientific concepts and expertise that underpin it. Finally, the article raises significant ethical and governance issues related to neurotechnology development and postdigital science that require concerted attention from education researchers

MLP (muscle LIM protein) as a stress sensor in the heart

Muscle LIM protein (MLP, also known as cysteine rich protein 3 (CSRP3, CRP3)) is a muscle-specific-expressed LIM-only protein. It consists of 194 amino-acids and has been described initially as a factor involved in myogenesis (Arber et al. Cell 79:221–231, 1994). MLP soon became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype (Arber et al. Cell 88:393–403, 1997). At this time, this was the first genetically altered animal model to develop this devastating disease. Interestingly, MLP was also found to be down-regulated in humans with heart failure (Zolk et al. Circulation 101:2674–2677, 2000) and MLP mutations are able to cause hypertrophic and dilated forms of cardiomyopathy in humans (Bos et al. Mol Genet Metab 88:78–85, 2006; Geier et al. Circulation 107:1390–1395, 2003; Hershberger et al. Clin Transl Sci 1:21–26, 2008; Knöll et al. Cell 111:943–955, 2002; Knöll et al. Circ Res 106:695–704, 2010; Mohapatra et al. Mol Genet Metab 80:207–215, 2003). Although considerable efforts have been undertaken to unravel the underlying molecular mechanisms—how MLP mutations, either in model organisms or in the human setting cause these diseases are still unclear. In contrast, only precise knowledge of the underlying molecular mechanisms will allow the development of novel and innovative therapeutic strategies to combat this otherwise lethal condition. The focus of this review will be on the function of MLP in cardiac mechanosensation and we shall point to possible future directions in MLP research