3,3-Dibromoflavanone, a synthetic flavonoid derivative for pain management with antidepressant-like effects and fewer side effects than those of morphine in mice.

In the pursuit of new lead compounds with fewer side effects than opioids, the novel synthetic phytochemical core, 3,3-dibromoflavanone (3,3-DBF), has emerged as a promising candidate for pain management. Acute assays demonstrated dose-dependent central and peripheral antinociceptive activity of 3,3-DBF through the µ-opioid receptor. This study aimed to explore repeated administration effects of 3,3-DBF in mice and compare them with morphine. Mice were treated with 3,3-DBF (30 mg/kg), morphine (6 mg/kg), or vehicle for 10 days, alongside single-treatment groups. Unlike morphine, 3,3-DBF demonstrated antinociceptive effects in the hot plate test without inducing tolerance. Locomotor activity and motor coordination tests (evaluated through the inverted screen and rotarod tests) revealed no significant differences between the 3,3-DBF-treated and control groups. The gastrointestinal transit assay indicated that 3,3-DBF did not induce constipation, in contrast to morphine. Furthermore, withdrawal signs assessed with the Gellert-Holtzman scale were not comparable to morphine. Additionally, 3,3-DBF exhibited antidepressant-like activity, reducing immobility time in the forced swimming and tail suspension tests, akin to imipramine. In summary, 3,3-DBF demonstrated antinociceptive effects without inducing tolerance or dependence and exhibited antidepressant properties. These findings highlight the potential of 3,3-DBF as a promising therapeutic agent for pain management and its comorbidities, offering advantages over morphine by minimizing side effects.

Investigating the efficacy of transcranial direct current stimulation on chronic pain management in endometriosis patients: A randomized controlled trial protocol.

INTRODUCTION: Similar to chronic pain conditions, individuals with endometriosis can be affected by central sensitization syndrome (CSS), which is characterized by a loss of analgesia and central amplification of pain. Transcranial direct current stimulation (tDCS) has shown potential as an effective intervention to improve pain generated by other chronic pain conditions impacted by CSS, such as fibromyalgia and chronic pelvic issues. This study aims to evaluate the effectiveness of tDCS on pain, fatigue, and quality of life among patients affected by endometriosis. METHODS: This is a single-center, parallel, double-blinded, randomized, controlled clinical trial protocol study. We aim to recruit 40 participants affected by endometriosis (active group, n = 20; sham group, n = 20). Anodal tDCS will be delivered at an intensity of 2mA, applied over the primary motor cortex for 20 minutes per day for 10 consecutive days. There will be four assessment times: 1 week before beginning the intervention; on the 10th day following the last tDCS session; and 1 and 2 months after the last tDCS session. Pain evaluated by the algometry will be the primary outcome. Pain intensity, quality of life, fatigue, and global perception of change will be the secondary outcomes. We will calculate the effects of the active versus sham stimulation on primary and secondary outcomes by using generalized estimated equations or mixed model analysis. The effect size calculation will represent the effect measure. We expect that only the active group show reductions in pain, fatigue, and quality of life. The results of this trial will produce an important first step in providing evidence on the effectiveness of neuromodulation for the management of pain and will provide data to support new studies on tDCS. REGISTRATION: Brazilian Clinical Trials Registry (RBR-4q69573).

Posterior insula repetitive transcranial magnetic stimulation for chronic pain in patients with Parkinson disease - pain type matters: A double-blinded randomized sham-controlled trial.

OBJECTIVES: Altered somatosensory processing in the posterior insula may play a role in chronic pain development and contribute to Parkinson disease (PD)-related pain. Posterior-superior insula (PSI) repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to have analgesic effects among patients with some chronic pain conditions. This study aimed at assessing the efficacy of PSI-rTMS for treating PD-related pain. METHODS: This was a double-blinded, randomized, sham-controlled, parallel-arm trial (NCT03504748). People with PD (PwP)-related chronic pain underwent five daily PSI-rTMS sessions for a week, followed by once weekly maintenance stimulations for seven weeks. rTMS was delivered at 10 Hz and 80% of the resting motor threshold. The primary outcome was a ≥ 30% pain intensity reduction at 8 weeks compared to baseline. Functionality, mood, cognitive, motor status, and somatosensory thresholds were also assessed. RESULTS: Twenty-five patients were enrolled. Mean age was 55.2 ± 9.5 years-old, and 56% were female. Nociceptive pain accounted for 60%, and neuropathic and nociplastic for 20% each. No significant difference was found for 30% pain reduction response rates between active (42.7%) and sham groups (14.6%, p = 0.26). Secondary clinical outcomes and sensory thresholds also did not differ significantly. In a post hoc analysis, PwP with nociceptive pain sub-type experienced more pain relief after active (85.7%) compared to sham PSI-rTMS (25%, p = 0.032). CONCLUSION: Our preliminary results suggest that different types of PD-related pain may respond differently to treatment, and therefore people with PD may benefit from having PD-related pain well characterized in research trials and in clinical practice.

Self-management of primary dysmenorrhea-related pain: cross-sectional study on non-pharmacological interventions.

Aim: Different nonpharmacological strategies are adopted to decrease primary dysmenorrhea (PD)-related pain. The present study aimed to verify women's use of nonpharmacological methods for pain and compare them with evidence from the literature.Materials & methods: A two-step study was conducted, comprising an online survey with 9144 women to assess nonpharmacological strategies for relieving PD-related pain, and a literature review on PubMed of verify the evidence of nonpharmacological methods.Results: Many women reported using heat therapy (61.5%), tea (42.4%) and massage (30.9%) to alleviate menstrual pain. However, the literature on these methods is limited.Conclusion: Several nonpharmacological methods are used by women to relieve PD-related pain and studies with low bias risk are needed to prove their effectiveness.

What is this article about This article explores how women manage menstrual pain, known as primary dysmenorrhea (PD), using non-drug methods. The study investigates the common self-care techniques women employ to ease their pain and compares these practices with scientific evidence.What were the results? The study found that many women use non-drug methods such as heat therapy (61.5%), tea (42.4%) and massage (30.9%) to relieve menstrual pain. Despite their popularity, sometimes the scientific evidence supporting the effectiveness of these methods is limited.What do these results mean? These results indicate that while women frequently use various self-care methods to manage menstrual pain, there is a need for more high-quality scientific studies to confirm whether these methods are truly effective. This highlights a gap between common practices and scientific effectiveness.

Combining Transcranial Direct Current Stimulation With Non-Invasive Interventions for Chronic Primary Pain: A Systematic Review and Meta-Analysis.

BACKGROUND: A growing number of studies has combined transcranial direct current stimulation (tDCS) with other non-invasive non-pharmacological therapies (NINPT) to enhance effects in pain reduction. However, the efficacy of these combined approaches in treating chronic primary pain (CPP) warrants thorough investigation. OBJECTIVE: This study aims to evaluate the efficacy of tDCS in conjunction with other NINPT in alleviating pain severity among CPP patients. METHODS: We conducted a systematic search for randomized controlled trials (RCTs) comparing the efficacy of tDCS combined with NINPT against control treatments in adult CPP patients. The search spanned multiple databases, including PubMed, EMBASE, LILACS, Scopus, Web of Science, and CENTRAL. RESULTS: Our systematic review included 11 RCTs with a total of 449 participants. In our meta-analysis, which comprised 228 participants receiving active-tDCS and 221 receiving sham-tDCS, we found a significant reduction in pain intensity (Standard Mean Difference = -0.73; 95% Confidence Interval (CI) = -1.18 to -0.27; P = .002) with the use of active-tDCS combined with NINPT. CONCLUSION: These findings substantiate the therapeutic potential of combining tDCS with other NINPT, highlighting it as an effective treatment modality for reducing pain intensity in CPP patients.

Neurobiological modulation with REAC technology: enhancing pain, depression, anxiety, stress, and quality of life in post-polio syndrome subjects.

Post-polio syndrome (PPS) brings new challenges for polio survivors, including muscle decline, pain, depression, and diminished quality of life. This study explored the potential of REAC neuromodulatory treatments to ease pain, improve mood, and enhance quality of life in PPS patients. 17 individuals with PPS (average age 54.8) received three REAC treatments: Neuro Postural Optimization, Neuro Psycho Physical Optimization, and Neuro Psycho Physical Optimization-Cervico Brachial. Pain, depression, anxiety, stress, and quality of life were assessed before and after using established scales. REAC treatments significantly reduced pain across various dimensions, along with depression, anxiety, and stress levels. Additionally, patients reported improved physical and psychological quality of life. This study suggests REAC neuromodulatory treatments as a promising non-invasive option to improve pain, emotional well-being, and quality of life in individuals with PPS.

Utilization of local pressure devices in pain management during injections: scoping review.

OBJECTIVE: to map scientific evidence regarding the use of local pressure devices in pain relief during injection procedures in patients. METHODS: scoping review, following the recommendations of the JBI Manual for Evidence Synthesis and PRISMA-ScR, with searches conducted in the PubMed, EMBASE, CINAHL, LILACS, and PsycINFO databases, without temporal restrictions and with a cutoff date of March 2023. RESULTS: a total of 1,514 studies were identified, with 20 articles included in the final sample. The ShotBlocker® device was utilized during subcutaneous and intramuscular injections in children and adults, proving beneficial in reducing pain, anxiety, and fear associated with the procedure. FINAL CONSIDERATIONS: the ShotBlocker® is a low-cost, easy-to-use device that can enhance nursing clinical practice during painful procedures. However, studies involving the Brazilian Pikluc® device are scarce. Further research involving both local pressure devices is recommended.

The Role of Virtual Reality and Artificial Intelligence in Cognitive Pain Therapy: A Narrative Review.

PURPOSE OF REVIEW: This review investigates the roles of artificial intelligence (AI) and virtual reality (VR) in enhancing cognitive pain therapy for chronic pain management. The work assesses current research, outlines benefits and limitations and examines their potential integration into existing pain management methods. RECENT FINDINGS: Advances in VR have shown promise in chronic pain management through immersive cognitive therapy exercises, with evidence supporting VR's effectiveness in symptom reduction. AI's personalization of treatment plans and its support for mental health through AI-driven avatars are emerging trends. The integration of AI in hybrid programs indicates a future with real-time adaptive technology tailored to individual needs in chronic pain management. Incorporating AI and VR into chronic pain cognitive therapy represents a promising approach to enhance management by leveraging VR's immersive experiences and AI's personalized tactics, aiming to improve patient engagement and outcomes. Nonetheless, further empirical studies are needed to standardized methodologies, compare these technologies to traditional therapies and fully realize their clinical potential.

Nonpharmacological Interventions for Treating Breastfeeding Nipple Pain: Systematic Review and Meta-Analysis.

Objective: To evaluate the efficacy and safety of nonpharmacological topical interventions for treating breastfeeding nipple pain. Methods: Randomized clinical trials (RCTs) assessing lactating women suffering from breastfeeding painful nipples were included. Primary outcomes were pain, healing process, and adverse events. A comprehensive search was conducted on June 02, 2023, without date or language restrictions. Methodological quality was assessed using the Cochrane risk of bias tool and the certainty of the evidence, the GRADE approach. Results: Nineteen RCTs with unclear to high risk of bias were included. There was uncertain evidence regarding the effects of photobiomodulation versus placebo on pain reduction (mean difference [MD] -0.15; 95% confidence interval [95% CI] -1 0.49 to 1.19; 139 participants, 2 RCTs). There are uncertainties concerning the effects of lanolin versus breast milk on pain (MD -1.80; 95% CI -2.43 to -1.17; 1 RCT; 180 participants), wound healing (MD 0.10; 95% CI -0.26 to -0.46; 1 RCT; 180 participants), and any adverse events (zero events in both groups). Similar effects were observed by the other interventions assessed. Conclusion: The evidence of nonpharmacological topical interventions for painful nipples is imprecise, and future RCTs with higher methodological quality are needed to support recommendations. Considering the accessibility and low cost of these alternative treatments, the findings of this evidence synthesis could support clinical decision-making and guide future research. PROSPERO CRD42020170320.

Effectiveness of Percutaneous Needle Electrolysis to Reduce Pain in Tendinopathies: A Systematic Review With Meta-Analysis.

CONTEXT: Tendon injuries are common disorders in both workers and athletes, potentially impacting performance in both conditions. This is why the search for effective treatments is continuing. OBJECTIVE(S): The objective of this study was to analyze whether the ultrasound-guided percutaneous needle electrolysis technique may be considered a procedure to reduce pain caused by tendinosis. EVIDENCE ACQUISITION: The search strategy included the PubMed, SCOPUS, CINAHL, Physiotherapy Evidence Database, SciELO, and ScienceDirect up to the date of February 25, 2024. Randomized clinical trials that assessed pain caused by tendinosis using the Visual Analog Scale and Numeric Rating Scale were included. The studies were evaluated for quality using the Cochrane Risk of Bias 2, and the evidence strength was assessed by the GRADEpro GDT. EVIDENCE SYNTHESIS: Out of the 534 studies found, 8 were included in the review. A random-effects meta-analysis and standardized mean differences (SMD) were conducted. The ultrasound-guided percutaneous needle electrolysis proved to be effective in reducing pain caused by tendinosis in the overall outcome (SMD = -0.97; 95% CI, -1.26 to -0.68; I2 = 58%; low certainty of evidence) and in the short-term (SMD = -0.83, 95% CI, -1.29 to -0.38; I2 = 65%; low certainty of evidence), midterm (SMD = -1.28; 95% CI, -1.65 to -0.91; I2 = 0%; moderate certainty of evidence), and long-term (SMD = -0.94; 95% CI, -1.62 to -0.26; I2 = 71%; low certainty of evidence) subgroups. CONCLUSION(S): The application of the ultrasound-guided percutaneous needle electrolysis technique for reducing pain caused by tendinosis appears to be effective. However, due to the heterogeneity found (partially explained), more studies are needed to define the appropriate dosimetry, specific populations that may benefit more from the technique, and possible adverse events.

Acupuncture for pediatric chronic pain: a systematic review.

OBJECTIVES: To survey, analyze and discuss the scientific evidence supporting the use of acupuncture and related techniques in the management of chronic pain in the pediatric population. SOURCES: A survey of databases (MEDLINE, Scopus and Scielo) was carried out with search strategies, following the PRISMA statement, without limits on publication dates and languages. Clinical studies (clinical trials, single-arm, and case series) were accepted for review if they included participants aged up to 22 years. Study quality was assessed by MMAT, and the randomized clinical trial was analyzed under the STRICTA criteria. SUMMARY OF THE FINDINGS: 2369 articles were retrieved. After excluding repetitions, 1335 underwent the initial selection. Only 16 articles were selected for full reading, of which 5 were included in the review, being two case series, two single-arm studies, and one randomized clinical trial. The articles were considered of good quality by the adopted criteria. CONCLUSION: The analyzed studies showed important clinical results such as the reduction of pain intensity, and improvement in school attendance and social life. However, there are many limitations in study design and sample size. Therefore, there is weak evidence to support the use of acupuncture in the context of pediatric chronic pain, but the positive results reinforce the need for further investigation of the topic with the conduct of larger and well-designed studies, to obtain more data and greater scientific conviction of the findings.

Nutrition and chronic musculoskeletal pain: A narrative review and directions for temporomandibular disorder research and management.

BACKGROUND: Recent evidence suggests neuro-immune mechanisms may link dietary patterns to chronic painful conditions (CPC). In the research field of oro-facial pain (OFP), studies focuses primarily on dietary mechanical limitations due to pain and dysfunction. OBJECTIVE: This narrative review aimed to overview the role of nutrition on CPC, with emphasis on temporomandibular disorder (TMD), enlightening OFP researcher on dietary assessment possibilities and providing directions for studies in the field of OFP and nutrition. METHODS: A PubMed database search was performed using the MeSH and non-MeSH descriptors: "temporomandibular joint disorder"; "orofacial pain"; "musculoskeletal pain"; "chronic pain disorders"; "nutrition"; "diet"; "dietary therapy"; "dietary intake" and "inflammation". No time restrictions were applied. Literature reviews, systematic reviews, meta-analyses and clinical and pre-clinical trials were included. RESULTS: Exogenous oxidants from unhealthy dietary patterns may contribute to peripheral and central pro-inflammatory immune signalling leading to peripheral and central sensitization. Furthermore, diets rich in bioactive compounds are suggested to contribute to pain management of CPC. High dietary intake of ultra-processed foods impacts the quality of the diet and shows adverse health outcomes. In this context, the role of nutrition on TMD remains overlooked. CONCLUSION: Considering diet may influence CPC, allied with the scarcity of studies evaluating the role of nutrition on TMD, well-designed clinical trials based on dietary assessments and measurements capable of evaluating food quality, UPF consumption and nutrient adequacy-added to serum nutrient levels evaluation-are suggested.

Cannabinoid products for pain management: recommendations from the São Paulo State Society of Anesthesiology.

There is growing interest in using cannabinoids across various clinical scenarios, including pain medicine, leading to the disregard of regulatory protocols in some countries. Legislation has been implemented in Brazil, specifically in the state of São Paulo, permitting the distribution of cannabinoid products by health authorities for clinical purposes, free of charge for patients, upon professional prescription. Thus, it is imperative to assess the existing evidence regarding the efficacy and safety of these products in pain management. In light of this, the São Paulo State Society of Anesthesiology (SAESP) established a task force to conduct a narrative review on the topic using the Delphi method, requiring a minimum agreement of 60% among panelists. The study concluded that cannabinoid products could potentially serve as adjuncts in pain management but stressed the importance of judicious prescription. Nevertheless, this review advises against their use for acute pain and cancer-related pain. In other clinical scenarios, established treatments should take precedence, particularly when clinical protocols are available, such as in neuropathic pain. Only patients exhibiting poor therapeutic responses to established protocols or demonstrating intolerance to recommended management may be considered as potential candidates for cannabinoids, which should be prescribed by physicians experienced in handling these substances. Special attention should be given to individual patient characteristics and the likelihood of drug interactions.

Evaluation of the effects of pregabalin and dexamethasone coadministration on preemptive multimodal analgesia and anxiety in third molar surgeries: a triple-blind randomized clinical trial.

OBJECTIVE: To evaluate the efficacy of pregabalin and dexamethasone coadministration in preemptive analgesia and anxiety control in lower third molar surgery. MATERIALS AND METHODS: A triple-blind, split-mouth clinical trial conducted with patients divided into two groups: control group, receiving placebo and dexamethasone, and test group, receiving pregabalin and dexamethasone preoperatively. The evaluated variables were pain, measured by the Visual Analog Scale (VAS), anxiety assessed through the State-Trait Anxiety Inventory (STAI) questionnaires, hemodynamic parameters [Blood Pressure (BP), Heart Rate (HR), Oxygen Saturation (SpO2)], and sedation assessed by the Ramsay scale. RESULTS: A total of 31 patients were included. The test group exhibited a significant reduction in pain at 2,4,6,8,12,16,24, and 48 h after surgery and in the consumption of rescue analgesics. Anxiety, evaluated by STAI and VAS, showed a significant decrease in the test group (p < 0.001). Additionally, there was a significant decrease in BP at most of the assessed time points (p < 0.05) and a significant reduction in HR at two different time intervals (p = 0.003 and p = 0.009), indicating a positive effect in the test group. There was no significant difference in SpO2 between the groups. Sedation assessment revealed a significant difference at all time points favoring the test group (p < 0.05). There were no significant postoperative adverse effects. CONCLUSIONS: Pregabalin coadministered with dexamethasone demonstrated significant efficacy in controlling postoperative pain and anxiety, as well as a sedative effect. CLINICAL RELEVANCE: The coadministration of pregabalin with dexamethasone may presents potential advantages in both pain modulation and psychological well-being of individuals undergoing third molar surgeries. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (REBEC), No. RBR-378h6t6.

Tramadol/Diclofenac Fixed-Dose Combination for Acute Pain Management: Bioavailability Assessment of a Generic Product.

The multimodal analgesia strategy for acute pain involves using 2 or more analgesic medications with distinct mechanisms of action. This study assessed the bioavailability and tolerability of 2 tramadol hydrochloride (50 mg)/diclofenac sodium (50 mg) fixed-dose combination formulations under fed conditions to attend the Brazilian regulatory requirements for generic product registration. An open-label, randomized, single-dose, 2-period, 2-way crossover trial was conducted, including healthy subjects of both sexes. Subjects received a single dose of either the test or reference formulation of tramadol/diclofenac fixed-dose combination tablets with a 7-day washout period. Blood samples were collected up to 36 hours after dosing for tramadol and 12 hours for diclofenac and quantified using a validated liquid chromatography-tandem mass spectrometry method. Of 56 subjects enrolled, 53 completed the study. The 90% confidence intervals for maximum plasma concentration and area under the concentration-time curve from time 0 to the last quantifiable concentration were within acceptable bioequivalence limits of 80%-125%. Considering the results presented in this study, the test formulation is bioequivalent to the reference formulation and could be interchangeable in medical practice.