Opioids and immune checkpoint inhibitors differentially regulate a common immune network in triple-negative breast cancer

BackgroundOpioids are the primary analgesics for cancer pain. Recent clinical evidence suggests opioids may counteract the effect of immune checkpoint inhibition (ICI) immunotherapy, but the mechanism for this interaction is unknown. The following experiments study how opioids and immunotherapy modulate a common RNA expression pathway in triple negative breast cancer (TNBC), a cancer subtype in which immunotherapy is increasingly used. This study identifies a mechanism by which opioids may decrease ICI efficacy, and compares ketamine, a non-opioid analgesic with emerging use in cancer pain, for potential ICI interaction.MethodsTumor RNA expression and clinicopathologic data from a large cohort with TNBC (N=286) was used to identify RNA expression signatures of disease. Various drug-induced RNA expression profiles were extracted from multimodal RNA expression datasets and analyzed to estimate the RNA expression effects of ICI, opioids, and ketamine on TNBC.ResultsWe identified a RNA expression network in CD8+ T-cells that was relevant to TNBC pathogenesis and prognosis. Both opioids and anti-PD-L1 ICI regulated RNA expression in this network, suggesting a nexus for opioid-ICI interaction. Morphine and anti-PD-L1 therapy regulated RNA expression in opposing directions. By contrast, there was little overlap between the effect of ketamine and anti-PD-L1 therapy on RNA expression.ConclusionsOpioids and ICI may target a common immune network in TNBC and regulate gene expression in opposing fashion. No available evidence supports a similar interaction between ketamine and ICI

Recent Advances in the Treatment of Opioid Use Disorder

PURPOSE OF REVIEW: Opioid use disorder (OUD) remains a national epidemic with an immense consequence to the United States\u27 healthcare system. Current therapeutic options are limited by adverse effects and limited efficacy. RECENT FINDINGS: Recent advances in therapeutic options for OUD have shown promise in the fight against this ongoing health crisis. Modifications to approved medication-assisted treatment (MAT) include office-based methadone maintenance, implantable and monthly injectable buprenorphine, and an extended-release injectable naltrexone. Therapies under investigation include various strategies such as heroin vaccines, gene-targeted therapy, and biased agonism at the G protein-coupled receptor (GPCR), but several pharmacologic, clinical, and practical barriers limit these treatments\u27 market viability. This manuscript provides a comprehensive review of the current literature regarding recent innovations in OUD treatment

Application of the novel Nalu™ Neurostimulation System for peripheral nerve stimulation

Peripheral nerve stimulation is an established treatment modality for chronic neuropathic pain. Over the last decade, with the advent of innovative devices and delivery platforms, peripheral nerve stimulation has evolved from invasive open surgeries to image-guided, minimally invasive percutaneous procedures. The authors hereby present a novel device, the Nalu™ Neurostimulation System (Nalu Medical, CA, USA), which has established its advantages in providing predictable and reliable peripheral nerve stimulation therapy for chronic neuropathic pain management. This novel device is effective in treating chronic pain conditions such as post-herniorrhaphy pain syndrome, intercostal neuralgia, post-laminectomy syndrome, and complex regional pain syndrome and holds great promise for the treatment of peripheral neuropathic pain

High-Frequency Impulse Therapy for Treatment of Chronic Back Pain: A Multicenter Randomized Controlled Pilot Study.

PurposeThis study aims to examine high-frequency impulse therapy (HFIT) impact on pain and function among patients undergoing care for chronic low back pain (CLBP).MethodsA pilot randomized-controlled trial of HFIT system versus sham was conducted across 5 orthopedic and pain center sites in California, USA. Thirty-six patients seeking clinical care for CLBP were randomized. Primary outcome was function measured by the Six Minute Walk Test (6MWT). Secondary outcomes were function (Timed Up and Go [TUG] and Oswestry Disability Index [ODI]), pain (Numerical Rating Scale [NRS]), quality of life (Patient Global Impression of Change [PGIC]), and device use. Patients were assessed at baseline and every week for 4 weeks of follow-up. Mann-Whitney U-test was used to analyze changes in each outcome. Repeated measures ANOVA was used to assess the effect of treatment over time.ResultsThe average age of subjects was 53.9 ± 15.7 (mean ± SD) years, with 12.1 ± 8.8 years of chronic low back pain. Patients who received an HFIT device had a significantly higher 6MWT score at weeks 2 [Cohen's d (95% CI): 0.33 (0.02, 0.61)], 3 [0.32 (0.01, 0.59)] and 4 [0.31 (0.01, 0.60)], respectively, as compared to their baseline scores (p < 0.05). Patients in the treatment group had significantly lower TUG scores at week 3 [0.30 (0.04, 0.57)] and significantly lower NRS scores at weeks 2 [0.34 (0.02, 0.58)] and 4 [0.41 (0.10, 0.67)] (p < 0.05).ConclusionA larger-scale RCT can build on the findings of this study to test whether HFIT is effective in reducing pain and improving function in CLBP patients. This study shows encouraging evidence of functional improvement and reduction in pain in subjects who used HFIT. The efficacy and minimally invasive nature of HFIT is anticipated to substantially improve the management of CLBP patients

High-Frequency Impulse Therapy for Treatment of Chronic Back Pain: A Multicenter Randomized Controlled Pilot Study.

PurposeThis study aims to examine high-frequency impulse therapy (HFIT) impact on pain and function among patients undergoing care for chronic low back pain (CLBP).MethodsA pilot randomized-controlled trial of HFIT system versus sham was conducted across 5 orthopedic and pain center sites in California, USA. Thirty-six patients seeking clinical care for CLBP were randomized. Primary outcome was function measured by the Six Minute Walk Test (6MWT). Secondary outcomes were function (Timed Up and Go [TUG] and Oswestry Disability Index [ODI]), pain (Numerical Rating Scale [NRS]), quality of life (Patient Global Impression of Change [PGIC]), and device use. Patients were assessed at baseline and every week for 4 weeks of follow-up. Mann-Whitney U-test was used to analyze changes in each outcome. Repeated measures ANOVA was used to assess the effect of treatment over time.ResultsThe average age of subjects was 53.9 ± 15.7 (mean ± SD) years, with 12.1 ± 8.8 years of chronic low back pain. Patients who received an HFIT device had a significantly higher 6MWT score at weeks 2 [Cohen's d (95% CI): 0.33 (0.02, 0.61)], 3 [0.32 (0.01, 0.59)] and 4 [0.31 (0.01, 0.60)], respectively, as compared to their baseline scores (p < 0.05). Patients in the treatment group had significantly lower TUG scores at week 3 [0.30 (0.04, 0.57)] and significantly lower NRS scores at weeks 2 [0.34 (0.02, 0.58)] and 4 [0.41 (0.10, 0.67)] (p < 0.05).ConclusionA larger-scale RCT can build on the findings of this study to test whether HFIT is effective in reducing pain and improving function in CLBP patients. This study shows encouraging evidence of functional improvement and reduction in pain in subjects who used HFIT. The efficacy and minimally invasive nature of HFIT is anticipated to substantially improve the management of CLBP patients

Treatment of knee osteoarthritic pain with platelet-rich plasma: a systematic review of clinical studies

Introduction: Knee osteoarthritis is a degenerative joint disease that is secondary to degradation of articular cartilage, reformation of subchondral bone through degradation and proliferation as well as presence of synovitis. Materials & methods: This systematic review was conducted and reported as per Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Results: A total of 30 of the 48 comparators showed statistically significant superiority with platelet-rich plasma (PRP) compared with a control, while the other 16 comparators showed no significant difference between PRP and the comparator. Conclusion: We can only recommend PRP for patients with early-stage osteoarthritis (I or II) and who are aged below 65, based on our findings. Based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) recommendations, while studies reviewed were randomized controlled studies, and therefore, high grade, due to variance in imprecision, risk of bias and inconsistency among the 37 studies, it would be reasonable to rate this paper as subjectively moderate

Intrathecal Drug Delivery Systems Survey: Trends in Utilization in Pain Practice

Background: The use of intrathecal drug delivery for chronic and cancer pain medicine has been established for decades. However, optimization and utilization of this technique still lag behind other modalities for pain control. Some of this may be due to variability of surgical technique, medication usage and education. It is currently unclear on whether or not practitioners follow available algorithms for the use of intrathecal drug delivery systems. Methods: A survey developed by the American Society of Pain and Neuroscience (ASPN) was sent to its members via email using the cloud-based . After 30 days of being available, 159 different providers responded to the survey that consisted of 31 various multiple choice and free response questions. Each question was not required and the number of responses to each varied from 128 to 159. Results: Approximately 9% of those who successfully received and opened the email containing the survey responded, likely due to a small number of providers working with intrathecal drug delivery systems. Eighty-six of respondents practice medicine in the United States, and 87% of the respondents were attending physicians. A majority of respondents, approximately 74%, were board certified in pain medicine with 69% of respondents being train in anesthesiology. The first and second most used medications for intrathecal pump trial were morphine and fentanyl, respectively. Most respondents, approximately 96%, provide pre-operative/intra-operative antibiotics. The most common first-choice medication for implanted intrathecal pumps was also morphine with the most common implanted location being the abdomen. Conclusion: Interestingly, there is currently fairly substantial variation in the way providers utilize intrathecal pump delivery for both chronic and cancer pain. There is variation from the training background of the providers providing care, to the pre-implantation trial medications, to where the pump is implanted for each patient, to if the patient has the option to give themselves boluses once implanted. Further research is needed to elucidate current and best practices for intrathecal drug delivery system trials, implantations, and utilization

Recent Advances in the Treatment of Opioid Use Disorder

PURPOSE OF REVIEW: Opioid use disorder (OUD) remains a national epidemic with an immense consequence to the United States\u27 healthcare system. Current therapeutic options are limited by adverse effects and limited efficacy. RECENT FINDINGS: Recent advances in therapeutic options for OUD have shown promise in the fight against this ongoing health crisis. Modifications to approved medication-assisted treatment (MAT) include office-based methadone maintenance, implantable and monthly injectable buprenorphine, and an extended-release injectable naltrexone. Therapies under investigation include various strategies such as heroin vaccines, gene-targeted therapy, and biased agonism at the G protein-coupled receptor (GPCR), but several pharmacologic, clinical, and practical barriers limit these treatments\u27 market viability. This manuscript provides a comprehensive review of the current literature regarding recent innovations in OUD treatment