Treatment Of Chronic Pain Research Articles

Infralimbic-basolateral amygdala circuit associated with depression-like not anxiety-like behaviors induced by chronic neuropathic pain and the antidepressant effects of electroacupuncture

Chronic pain, such as neuropathic pain, can lead to anxiety, depression, and other negative emotions, thereby forming comorbidities and increasing the risk of chronic pain over time. Both the infralimbic amygdala (IL) and the basolateral amygdala (BLA) are significantly associated with negative emotions and pain, and they are known to have reciprocal connections. However, the role of IL-BLA circuit pathways in neuropathic pain-induced anxiety and depression remains unexplored. Electroacupuncture (EA) is frequently employed in the treatment of chronic pain and emotional disorders. However, The mechanism by which EA mediates its analgesic and emotion-alleviating effects via the IL-BLA circuit remains uncertain. Here, we used chemogenetic manipulation combined with behavioral tests to detect pain induced anxiety-like and depression-like behaviors. We observed that activation of the IL-BLA circuit by chemogenetic activation induced depression-like behavior of mice. Additionally, we discovered that chemogenetic activation of the IL-BLA circuit successfully prevented the beneficial effects of EA on depression-like behavior brought on by chronic pain in mice with spared nerve injury (SNI). We discovered that SNI-induced depression-like behavior could be mitigated by inhibiting the circuit, and EA had a comparable depressive-relieving effect. Furthermore, the IL-BLA circuit's activation or inhibition had no effect on the anxiety-like feelings brought on by SNI. Overall, our findings identify a specific neural circuit that selectively regulates pain-induced depression-like emotions, without affecting pain-induced anxiety-like emotions. This discovery offers a precise target for future treatments of comorbid pain and depression and provides a plausible explanation for the efficacy of EA in treating depression-like emotions associated with chronic pain.

Prevalence and treatment of chronic musculoskeletal pain focused on service gaps: a comparative analysis by age group and body part

Background Occupational health, grounded in occupational medicine, aims to enhance the well-being and labor productivity of the working population. Within this realm, there has been growing concern over the increasing instances of labor loss due to diminished physical capacity and the rise in musculoskeletal disorders. Chronic pain is also associated with musculoskeletal disorders. Another pressing issue related to chronic musculoskeletal pain was needed assistance services are underutilized, is referred to as a “service gap”. Understanding trends based on age and affected regions of the body is indispensable for developing strategies to address chronic musculoskeletal pain in workers. This study aimed to elucidate age-specific trends in the prevalence and number of pain sites in chronic musculoskeletal pain as well as the patterns of treatment during chronic musculoskeletal pain, categorized by age and affected site. Methods This study was conducted in December 2022 in contract to Cross Marketing Inc. The survey began on December 12, 2022 and ended on December 15, 2022. An online survey was administered to 1,946 participants (973 women and 973 men), and responses were collected, ensuring a roughly equal distribution of samples among men and women across six age groups ranging from their 20 to 70 s. The survey inquired about the presence of chronic pain in each of the eight body parts and the adoption of five different treatments when experiencing pain. Statistical analysis was performed using the chi-square test, with the measurement data categorized by age group and body part. Results The results indicated a significantly higher prevalence of chronic pain at three or more sites among individuals in their 30 s: the prevalence of pain at each of the eight body sites varied with age. Approximately half of the participants did not engage in specific treatments during episodes of chronic pain. The presence or absence of treatment showed no significant differences according to affected site or age group. This study revealed age- and body part-related relationships with chronic musculoskeletal pain in middle-aged patients and highlighted healthcare service gaps in its management in Japan.

Protocol for remote Tai Chi and wellness for PTSD and pain in veterans

ABSTRACT Background: Posttraumatic stress disorder (PTSD) is a debilitating psychological disorder that is associated with a host of psychosocial and health ailments, including chronic pain. Although evidence-based psychological therapies are recommended as first-line PTSD treatments, a large proportion of individuals either drop out and/or do not achieve a therapeutic response. PTSD is increasingly recognized as a systemic disorder that impacts both physical and mental health, and mind-body approaches, such as Tai Chi, have shown promise. However, to date there have been no randomized clinical trials examining Tai Chi as a treatment for PTSD. Objective: To conduct a fully remote two-phased study designed to adapt, refine, and standardize two group treatments, Tai Chi and a Wellness comparison, for Veterans diagnosed with PTSD and chronic pain. Method: We deploy the project in two phases. In Phase One, we adapt both interventions for delivery via a videoconferencing platform. We then pilot the interventions in a ‘dry run’ with non-random assignment of 12 participants to Tai Chi or a Wellness comparison group. In Phase Two, we randomize 36 participants to one of the two group interventions. The feasibility and acceptability of the two remotely delivered interventions and assessment protocols are evaluated. Conclusions: This is the first study to our knowledge to evaluate the feasibility, acceptability, adherence, and participant burden of the Tai Chi and Wellness comparison interventions for PTSD and chronic pain in Veterans. This information will facilitate the development of a future large, randomized control trial to evaluate the efficacy of Tai Chi to address PTSD and chronic pain in Veterans.

Biopsychosocial Approaches for the Management of Female Chronic Pelvic Pain: A Systematic Review.

Current guidelines recommend biopsychosocial-informed treatment for chronic pelvic pain (CPP). The objective of this systematic review was to describe the available biopsychosocial approaches for the treatment of CPP, and the outcomes reported, to understand how guideline-recommended treatments can be applied. MEDLINE, CINAHL, PsycINFO, EMBASE, Emcare, AMED and Cochrane trial registries were searched (inception to 17 November 2023). CPP Studies in women where the principal treatment modality was a biopsychosocial approach were included. Prospero registration: CRD42022374256. Data extraction included study setting, population, study design, intervention characteristics and outcome measures and is described via a narrative synthesis. The review included 14 RCTs (871 patients) and identified four broad intervention categories (Acceptance Commitment Therapy n = 2, Cognitive Behavioural Therapy n = 6, Mindfulness-based approaches n = 2, and Physiotherapy-based interventions n = 4). Pain science education (PSE) and, exposure/engagement with valued activity were recognised as important aspects of treatment regardless of intervention type. The most utilised outcomes were pain reduction and emotional functioning, with all studies reporting improvements in these domains. Heterogeneity in outcomes prevented efficacy comparison. High risk of bias was identified in six studies (1/4 physiotherapy-based approaches, 2/6 CBT, 1/2 ACT and 2/2 mindfulness-based interventions). CBT and ACT-based biopsychosocial approaches were found effective in reducing pain and improving psychometric outcomes for CPP. Evaluation indicated PSE, and exposure/engagement in valued activity are important components of biopsychosocial management. Outcome heterogeneity needs to be addressed in future trials.

Pharmacological Pain Treatment in Older Persons.

Pharmacological pain treatment in older persons is presented by a multi-disciplinary group of European pain experts. Drugs recommended for acute or chronic nociceptive pain, also for neuropathic pain and the routes of administration of choice are the same as those prescribed for younger persons but comorbidities and polypharmacy in older persons increase the risk of adverse effects and drug interactions. Not all drugs are available or authorised in all European countries. For mild-to-moderate pain, non-opioids including paracetamol and non-steroidal anti-inflammatory drugs are first-line treatments, followed by nefopam and metamizole. Codeine, dihydrocodeine and tramadol are prescribed for moderate to severe pain and 'strong' opioids, including morphine, hydromorphone, oxycodone, fentanyl, buprenorphine, methadone and tapentadol, for severe pain. Chronic neuropathic pain treatment relies on coanalgesics, including anti-epileptics (gabapentinoids) and anti-depressants with additional option of topical lidocaine and capsaicine. The choice of analgesic(s) and the route of administration should be guided by the pain characteristics, as well as by the patient's comorbidities, organ function and medications. Several directions have been highlighted to optimise pharmacological pain management in older individuals: (1) before starting pain treatment adequately detect and assess pain and always perform a full geriatric assessment, (2) consider kidney function systematically to adjust the doses of analgesics and avoid the risks of overdose, (3) start with the lowest dose of an analgesic and increase it gradually under the control of the effect, (4) involve the older persons and family in their treatment, (5) reevaluate pain regularly during treatment and (6) combine pharmacological treatment with non-pharmacological approaches.

Comparison of the clinical efficacy on chronic abdominal wall pain between trigger-point electroacupuncture and transversus abdominis plane block

To compare the clinical efficacy between trigger-point (TrP) electroacupuncture and transversus abdominis plane (TAP) block in treatment of chronic abdominal wall pain (CAWP). A total of 62 CAWP patients were randomly divided into a TrP electroacupuncture group (31 cases, 1 case dropped off) and a TAP block group (31 cases, 1 case dropped off). Electroacupuncture at trigger points was delivered in the TrP electroacupuncture group, and TAP block was administered under ultrasonic guidance in the TAP block group. Separately, the score of the numerical pain rating scale (NRS) was observed before treatment and in 1 week, 1 month and 3 months after treatment；the scores of the self-rating anxiety scale (SAS) and the self-rating depressive scale (SDS) observed before treatment and in 1 week and 3 months after treatment；and the score of the short form 36 questionnaire (SF-36) was observed before treatment and in 3 months after treatment. The utilization rate of remedial drugs was recorded during follow-up visit. The clinical efficacy was compared. At each time point after treatment, NRS score decreased in comparison with that before treatment (P<0.05), the scores of SAS and SDS 1 week and 3 months after treatment were reduced (P<0.05) and the each item score of SF-36 increased (P<0.05) 3 months after treatment of each group. Compared with the outcomes in the TAP block group, NRS scores were reduced 1 month and 3 months after treatment respectively (P<0.05), the scores of SAS and SDS decreased (P<0.05) and SF-36 score was elevated (P<0.05) 3 months after treatment in the TrP electroacupuncture group. There was no significant difference in the utilization rate of remedial drugs between the two groups. The clinical efficacy of the TrP electroacupuncture group (96.7%) was superior to that of the TAP block group (83.3%, P<0.05). Both TrP electroacupuncture and TAP block can markedly relieve pain, attenuate the emotional symptoms of anxiety and depression and improve the quality of life in the patients with chronic abdominal wall pain. The clinical efficacy of TrP electroacupuncture is better than that of TAP block 3 months after treatment.

Expert consensus on diagnosis and treatment of chronic pelvic pain

Expert consensus on diagnosis and treatment of chronic pelvic pain

IL-10 Stimulates Microglia and Neurons to Produce Endogenous Opioid Peptides and Reduce Neuro-Inflammatory Chronic Pain

Chronic pain, persisting beyond three months, affects millions worldwide with no effective treatments. While some anti-inflammatory cytokines like IL-4 can trigger macrophages to produce pain-relieving opioid peptides, the role of IL-10 in this process remains unexplored. This study investigates IL-10's potential to stimulate opioid peptide production in neurons and glial cells and reduce pain. Using immunofluorescent staining, enzyme immunoassays, and the Von Frey test, we examined cells treated with LPS and cytokines, and assessed pain reduction in mouse models. Our findings suggest that IL-10 can trigger neurons and microglia to produce opioid peptides, albeit less efficiently than IL-4. These results indicate a potential new target for chronic pain treatment, combining IL-4 and IL-10 therapies, offering a promising alternative to current pain management strategies.

ABORDAGEM FISIOTERAPÊUTICA NA REABILITAÇÃO DE PACIENTES IDOSOS COM DORES CRÔNICAS

Chronic pain is a complex and multifaceted condition that affects millions of people around the world, posing a significant challenge to healthcare systems and patients’ quality of life. In the context of an aging population, chronic pain becomes even more prevalent and impactful, requiring effective and personalized therapeutic approaches. This study is a bibliographical review, of a qualitative nature, including studies published from 2015 to 2024, selected through the PubMed, Scielo and Lilacs databases. 100 articles were found, 60 of which met the previously established inclusion criteria . The results were significant, with the association of conventional physiotherapy with new functional techniques, strengthening training or complementary therapies to reduce pain. It is concluded that physiotherapy is a great ally for the treatment of chronic pain, even in some cases being non-specific, but highlighting the importance of new experimental studies.

Arginine vasopressin induces analgesic effects and inhibits pyramidal cells in the anterior cingulate cortex in spared nerve injured mice.

Neuropathic pain (NP) is a severe disease caused by a primary disease or lesion affecting the somatosensory nervous system. It`s reported that NP is related to the increased activity of glutamatergic pyramidal cells and changed neural oscillations in the anterior cingulate cortex (ACC). Arginine vasopressin (AVP), a neurohypophyseal hormone, has been shown to cause pain-alleviating effects when applied to peripheral system. However, the extent to which, and the mechanisms by which, AVP induces analgesic effects in the central nervous system remain unclear. In the present study, we observed that intranasal delivery of AVP inhibited mechanical pain, thermal pain and spontaneous pain sensitivity in mice with spared nerve injury. Meanwhile, AVP application exclusively reduced the FOS expression in the pyramidal cells but not interneurons in the ACC. In vivo electrophysiological recording of the ACC further showed that AVP application not only inhibited the theta oscillation in local field potential analysis, but also reduced the firing rate of spikes of pyramidal cells in the ACC in neuropathic pain mice. In summary, AVP induce analgesic effects by inhibiting neural theta oscillations and the spiking of pyramidal cells of the ACC in mice with neuropathic pain, which should provide new potential noninvasive methods for clinical treatment of chronic pain.

An early economic analysis of medical cannabis for the treatment of chronic pain

ABSTRACT Background Cannabis-based medicinal products (CBMPs) are increasingly demonstrating effectiveness in treating a wide range of conditions, with a relatively high safety profile in clinical usage compared to other prescription pain medications and few contraindications. Consultation and other prescription-related costs are, at present, higher for CBMPs than for some other treatment options, leading to some concern around wider prescribing. Research design and Methods An early cost-effectiveness model was developed to estimate the impact of prescribing CBMPs alone and/or in addition to analgesics, physiotherapy, and cognitive behavioral therapy for chronic pain in the UK for 1 year. Results Due to their comparative effectiveness, CBMPs were found to be cost saving. Various scenarios were model tested; in all scenarios where CBMPs decrease pain-level states, less resource use is required. Increased efficacy of 5% was conservatively assumed based on current Real-World Evidence. In this scenario, CBMPs were significantly more cost-effective, and as costs relating to the prescribing of these continue to fall, relative savings are predicted to increase. Conclusion These findings highlight the substantial cost saving that CBMPs may represent for the treatment of chronic pain patients, and the benefits for healthcare providers as a treatment for this often hard-to-treat population.

A randomized clinical trial of emotional freedom techniques for chronic pain: Live versus self-paced delivery with 6-month follow-up.

Chronic pain represents a major global healthcare crisis, and current treatments are limited in effectiveness and safety. Emotional freedom techniques (EFTs) show promise as a potential psychological treatment. The current study investigated the effect of a randomized clinical trial of EFT for chronic pain in a sample of 147 adult chronic pain sufferers (89.9% female; mean 54.63 years). Participants engaged in a 6-week EFT programme (either online self-paced or in-person). The per-protocol analysis indicated pain severity and interference scores were significantly lower at the end of treatment for the EFT group compared to waitlist, and these were sustained at follow-up. There were no differences between the in-person or self-paced programmes at follow-up for pain severity and interference. Somatic symptoms were significantly lower after EFT, although no further differences at follow-up. Quality of life scores were significantly higher after EFT, which were sustained at follow-up, and no differences between two styles of programme. No significant effects were found for anxiety, depression, happiness or satisfaction with life across the 6-week programmes for either style of delivery or at follow-up. These are discussed in terms of clinical score meanings. Intent-to-treat analysis was consistent with the per-protocol analyses. Limitations of the study are identified and future directions are discussed. Findings offer early promise for EFT as a potentially effective pain management strategy, as well as support for online intervention without compromising treatment outcomes. An emerging body-based intervention for chronic pain may be a possible solution for remote clients who cannot attend in-person sessions. In this clinical trial Emotional Freedom Techniques (EFT) significantly reduced chronic pain severity and interference, and there were no differences between and online self-paced program toan online in-person EFT intervention. Both were equally effective, also enhancing quality of life without compromising outcomes. The results were significant at 6-month follow-up/. These findings highlight a body-based approach as a promising, accessible pain management strategy, and highlights that online programs may be part of the solution for chronic pain patients.

In vitro Cyclooxygenase inhibitory activity and GC-MS profiling of bioactive compounds in Bauhinia racemosa Lam.

Non-steroidal anti-inflammatory drugs (NSAIDs) are a common treatment for chronic pain and inflammation. While NSAIDs have been shown to reduce inflammation and pain associated with them, they have an array of side effects. Researchers investigated the COX inhibitory action of NSAIDs. They revealed that there are two distinct COX enzymes: COX-1 and COX2. Developing COX inhibitors has remained critical for producing innovative and safe anti-inflammatory drugs. Bauhinia racemosa Lam belonging to the family Fabaceae has a wide range of medicinal properties. The plant is used to treat various diseases in traditional medicine, but there is less knowledge based on clinical efficacy as an anti-inflammatory agent. In the present study Bauhinia racemosa Lam hydroalcoholic extract were screened for COX inhibition and GC-MS analysis was done to screen phytochemicals. The results obtained were found to inhibit 89% of COX activity significantly as compared to standard drug (Diclofenac sodium). GC-MS analysis revealed a total of ten potent bioactive compounds. The samples were identified by comparing retention time and peak area to literature and interpreting mass spectra. Results observed from the study suggest that the hydroalcoholic extract of Bauhinia racemosa Lam possess anti-inflammatory activity and can be utilized as an alternate source for NSAIDs. Keywords: COX, Bauhinia racemosa Lam, Anti-inflammatory, NSAIDs.

Effect of endoscopic ultrasound guided celiac plexus block on the palliation of pain in chronic pancreatitis (EPOCH Trial): study protocol for a randomized multicenter sham-controlled trial {1}

BackgroundCeliac plexus block has been commonly utilized for the treatment of chronic pancreatitis-associated abdominal pain. Prospective studies suggest efficacy in 30 to 50% of patients, although no randomized sham-controlled trials have been performed. The objective of this study is to assess the effect of endoscopic ultrasound (EUS)-guided celiac plexus block on abdominal pain in patients with documented chronic pancreatitis. MethodsThis is a two-arm randomized sham-controlled trial with blinded evaluators. The study will be conducted at multiple academic sites in the United States who are members of the United States Pancreatic Disease Study Group (USPG). Patients referred for EUS to exclude chronic pancreatitis as a cause of abdominal pain as well as those with established painful chronic pancreatitis undergoing EUS for another indication will be eligible. At the time of EUS with confirmation of chronic pancreatitis by standard EUS diagnostic criteria, patients will be randomized to either celiac plexus block or sham whereby an anesthetic and steroid combination will be injected into the celiac plexus or saline will be injected into the gastric lumen with the same type of needle as used for celiac plexus block, respectively. The main outcome measure will be a 50% reduction in abdominal pain using the Brief Pain Inventory Short Form (BPI-SF) at 1 month post-intervention. A number of secondary outcomes will be measured including visual analog scale (VAS), Comprehensive Pain Assessment Tool Short Form (COMPAT-SF) pain scores, and quality of life using a pancreas-specific validated measure (PANQOLI).DiscussionIn this study, the effect of celiac plexus block on abdominal pain in patients with chronic pancreatitis will be compared to a sham intervention. This randomized trial will offer a definitive assessment of the role of celiac plexus block for the treatment of abdominal pain in this setting.Trial registration {2}ClinicalTrials.gov NCT 06178315. Registered on December 21, 2023

Veterans in Northern Ireland: Evaluation of chronic pain experience, service type, and physical and mental health functioning

Background Chronic pain is common and associated with disruptions in quality of life (QoL) and psychosocial functioning. These issues are particularly pronounced in veterans, although data in this regard primarily come from the United States Veterans Affairs System, meaning less is known regarding veterans of other countries and regions. The present study evaluated veterans living in Northern Ireland (NI), a region with historic high rates of both chronic pain and psychosocial difficulties associated with the decades-long period of civil and military conflict preceding the 1999 armistice (the Good Friday Agreement). Unique to the Northern Ireland military operation was the initiation of Home Service battalions comprised of local recruits, a role with increased risk due to the conflict’s nature and the fact that they were serving as a military and security presence in their home region. Methods A cross-sectional assessment of veterans living in Northern Ireland ( N = 722) provided details of service type (Home Service vs other service), current health conditions (including chronic pain), and current psychosocial functioning (including physical and mental health QoL, anxiety, depression, and post-traumatic stress disorder [PTSD] symptoms). Results Findings indicated that those with chronic pain had worse QoL, anxiety, depression, and PTSD. Those with chronic pain were also more likely to have served in the Home Services, be unemployed, and be receiving disability payment. Contrary to hypotheses, there was no interaction between chronic pain and service type. Conclusions These results extend previous work with veterans to the unique circumstances of a post-conflict military that engaged in operations within its own country and underscore the need for coordinated, efficacious interventions for co-morbid chronic pain and anxiety, depression, and PTSD.

Trifluoro-Icaritin Ameliorates Neuroinflammation Against Complete Freund's Adjuvant-Induced Microglial Activation by Improving CB2 Receptor-Mediated IL-10/β-endorphin Signaling in the Spinal Cord of Rats.

The underlying pathogenesis of chronic inflammatory pain is greatly complex, but the relevant therapies are still unavailable. Development of effective candidates for chronic inflammatory pain is highly urgent. We previously identified that trifluoro-icaritin (ICTF) exhibited a significant therapeutic activity against complete Freund's adjuvant (CFA)-induced chronic inflammatory pain, however, the precise mechanisms remain elusive. Here, the paw withdrawal threshold (PWT), paw withdrawal latency (PWL), and CatWalk gait analysis were used to determine the pain-related behaviors. The expression and co-localization of pain-related signaling molecules were detected by Western blot and immunofluorescence staining. Our results demonstrated that ICTF (3.0mg/kg, i.p.) effectively attenuated mechanical allodynia, thermal hyperalgesia and improved motor dysfunction induced by CFA, and the molecular docking displayed that CB2 receptor may be the therapeutic target of ICTF. Furthermore, ICTF not only up-regulated the levels of CB2 receptor, IL-10, β-endorphin and CD206, but also reduced the expression of P2Y12 receptor, NLRP3, ASC, Caspase-1, IL-1β, CD11b, and iNOS in the spinal cord of CFA rats. Additionally, the immunofluorescence staining from the spinal cord showed that ICTF significantly increased the co-expression between the microglial marker Iba-1 and CB2 receptor, IL-10, β-endorphin, respectively, but markedly decreased the co-localization between Iba-1 and P2Y12 receptor. Conversely, intrathecal administration of CB2 receptor antagonist AM630 dramatically reversed the inhibitory effects of ICTF on CFA-induced chronic inflammatory pain, leading to a promotion of pain hypersensitivity, abnormal gait parameters, microglial activation, and up-regulation of P2Y12 receptor and NLRP3 inflammasome, as well as the inhibition of CB2 receptor and IL-10/β-endorphin cascade. Taken together, these findings highlighted that ICTF alleviated CFA-induced neuroinflammation by enhancing CB2 receptor-mediated IL-10/β-endorphin signaling and suppressing microglial activation in the spinal cord, and uncovered that CB2 receptor may be exploited as a novel and promising target for ICTF treatment of chronic inflammatory pain.

Psychosocial Treatment Techniques to Augment the Impact of Occupational Therapy Interventions for Chronic Low Back Pain among School Teachers

Background: School teachers perform numerous tasks that contribute to low back pain and affect their activities of daily living, social and vocational abilities. Low back pain is multidimensional in nature constituting physical, psychological and social components. Psychosocial variables pose as an obstacle to rehabilitative recovery and have a role in development of chronicity, these factors are often neglected in the rehabilitation process, the present study integrates psychosocial factors with musculoskeletal factors and utilizes a rehabilitation program that focuses on overall recovery. Objectives: This study aims to find effective treatment for psychosocial variables and examines the physical and psychosocial changes that occur in school teachers suffering with CLBP when they receive occupational therapy augmented with psychosocial intervention. The intervention targets anxiety, perceived stress, and self-efficacy. Methodology: The study sample consisted of 60 school teachers, half of the sample was enrolled for occupational therapy intervention and other half for occupational therapy intervention augmented with psychosocial treatment techniques. Results: At post-treatment participants in the occupational therapy augmented with psychosocial treatment group showed significant difference in measures of anxiety, perceived stress and self-efficacy, pain intensity, pain severity, pain disability and 5-minute walk test distance compared to participants who received occupational therapy treatment only. The two groups did not differ significantly in finger-to-floor test. Conclusion: The findings of the study suggest that augmenting psychosocial variables is beneficial to person-environment factors of disability and result in better rehabilitation outcomes in terms of both psychosocial variables as well as pain related variables.

Clinical Efficacy of Auricular Vagus Nerve Stimulation in the Treatment of Chronic and Acute Pain: A Systematic Review and Meta-analysis.

Current guidelines for pain treatment recommend a personalized, multimodal and interdisciplinary approach as well as the use of a combination of drug and non-drug therapies. Risk factors for chronification should already be reduced in patients with acute pain, e.g., after surgery or trauma. Auricular vagus nerve stimulation (aVNS) could be an effective non-drug therapy in the multimodal treatment of chronic and acute pain. The aim of this systematic review and meta-analysis is to evaluate the clinical efficacy and safety of aVNS in treating chronic and acute pain conditions. A systematic literature search was performed regarding the application of auricular electrical stimulation in chronic and acute pain. Studies were classified according to their level of evidence (Jadad scale), scientific validity and risk of bias (RoB 2 tool) and analyzed regarding indication, method, stimulation parameters, duration of treatment and efficacy and safety. A meta-analysis on (randomized) controlled trials (using different comparators) was performed for chronic and acute pain conditions, respectively, including subgroup analysis for percutaneous (pVNS-needle electrodes) and transcutaneous (tVNS-surface electrodes) aVNS. The visual analog pain scale (VAS) was defined as primary efficacy endpoint. A total of n = 1496 patients were treated with aVNS in 23 identified and analyzed studies in chronic pain, 12 studies in acute postoperative pain and 7 studies in experimental acute pain. Of these, seven studies for chronic pain and six studies for acute postoperative pain were included in the meta-analysis. In chronic pain conditions, including back pain, migraine and abdominal pain, a statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control treatment with an effect size Hedges' g/mean difference of - 1.95 (95% confidence interval [CI]: - 3.94 to 0.04, p = 0.008) could be shown and a more favorable effect in pVNS compared to tVNS (- 5.40 [- 8.94; - 1.85] vs. - 1.00 [- 1.55; - 0.44]; p = 0.015). In acute pain conditions, single studies showed significant improvements with aVNS, e.g., in kidney donor surgery or tonsillectomy but, overall, a non-statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control with - 0.70 [- 2.34; 0.93] (p = 0.15) could be observed in the meta-analysis. In acute pain results vary greatly between studies depending especially on co-medication and timepoints of assessment after surgery. A significant reduction in analgesics or opiate intake was documented in most studies evaluating this effect in chronic and acute pain. In 3 of the 12 randomized controlled trials in patients with chronic pain, a sustainable pain reduction over a period of up to 12months was shown. Overall, aVNS was very well tolerated. This systematic review and meta-analysis indicate that aVNS can be an effective and safe non-drug treatment in patients with specific chronic and acute postoperative pain conditions. Further research is needed to identify the influence of simulation parameters and find optimal and standardized treatment protocols while considering quality-of-life outcome parameters and prolonged follow-up periods. A more standardized approach and harmonization in study designs would improve comparability and robustness of outcomes.

Efficacy of antidepressants in the treatment of chronic nonspecific low back pain: a systematic review and meta-analysis.

Aim: This study reassesses the efficacy and safety of antidepressants in treating nonspecific chronic low back pain (NCLBP).Materials & methods: A systematic review was conducted following PRISMA guidelines, including randomized clinical trials (RCTs) from PubMed, Embase, Scopus, LILACS, SciELO and Cochrane CENTRAL, published through August 2024. Studies compared antidepressants with placebo or active comparators. The primary outcomes were pain relief and quality of life. Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42023307516.Results: Nine RCTs involving 1758 patients were analyzed. The antidepressants examined included duloxetine, escitalopram, bupropion, amitriptyline, imipramine and desipramine. Duloxetine 60mg significantly reduced pain (MD=-0.57; 95% CI=-0.78 to -0.36) and improved quality of life compared with placebo, with side effects that were generally tolerable. Notably, higher doses of duloxetine (120mg) were associated with an increase in adverse events. However, other antidepressants like amitriptyline and escitalopram demonstrated only modest or inconsistent effects.Conclusion: Duloxetine at 60mg provides consistent pain relief and improves the quality of life in NCLBP, but higher doses increase adverse events. Escitalopram might offer modest benefits but should be considered a third-line treatment. Other antidepressants, such as amitriptyline, bupropion, imipramine and desipramine, have limited evidence supporting their efficacy and are associated with adverse effects.

Development of Tetrahydroquinoline-Based Inhibitors for Chronic Pain.

Chronic pain affects a substantial portion of the population, posing a significant health challenge. Current treatments often come with limitations and side effects, necessitating novel therapeutic approaches. Our study focuses on disrupting the Cav3.2-USP5 interaction as a strategy for chronic pain management. Through structure-activity relationship studies of a tetrahydroquinoline (THQ) scaffold, we identified a family of lead molecules that demonstrated potent inhibition of the Cav3.2-USP5 interaction. In vitro pharmacokinetic assessments and in vivo studies support the efficacy and drug-like properties of the lead compounds in mouse models of acute and chronic pain. Dependence on the Cav3.2 channels was validated in Cav3.2 null mice, consistent with the proposed mode of action of these small molecules. These findings provide a novel chronic pain treatment strategy, highlighting the potential of these small molecules for further development.