Treatment Of Chronic Pain Research Articles

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.

Tolerance, interdose withdrawal symptoms, and craving predict prescription opioid-use disorder severity in chronic pain patients: A three-wave prospective study

The DSM-5-TR diagnostic criteria for Prescription Opioid-Use Disorder (POUD) have undergone significant changes when using opioids medically supervised. However, there is a lack of research supporting these changes. This prospective study aimed to analyze the influence of tolerance, withdrawal symptoms, and craving on the severity of POUD in chronic pain population on long-term opioid therapy. Initial individual interviews and follow-ups at 6 and 12 months were conducted on 62 patients to assess tolerance, withdrawal symptoms, craving, and POUD severity. Information on sociodemographic, clinical, and psychological variables was also collected. Unadjusted and covariate-adjusted multinomial repeated measures mixed models were run. Results showed that, compared to not having POUD, tolerance was the sole variable that significantly predicted mild disorder, while interdose withdrawal symptoms, craving, depressive symptoms, and younger age predicted moderate-severe POUD. The effect of time was also significant in predicting moderate-severe POUD, increasing rates at 6- and 12-month follow-ups compared to initial assessment. These findings highlight that maintaining opioid therapy over time is associated with an increased likelihood of having a more severe disorder. Furthermore, although tolerance and withdrawal symptoms have been removed from POUD diagnosis, their assessment and early management remain critical even during supervised opioid treatment for 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.

Many randomized trials in a large systematic review were not registered and had evidence of selective outcome reporting: a metaepidemiological study

ObjectivesThe primary objectives were to describe characteristics of trial registration in the chronic low back pain (CLBP) field and assess the association of trial registration status (registered vs unregistered, prospectively registered vs retrospectively registered) with risk of bias, sufficient sample size, quality of reporting, and treatment effect estimates. Secondary objectives were to describe trial registration consistency with the final report and assess its association with risk of bias, sufficient sample size, and treatment effect estimates. Study Design and SettingA cross-sectional metaepidemiological study of trials included in a large Cochrane review on exercise treatments for CLBP. We extracted relevant trial and registration information and assessed trials’ risk of bias using the Cochrane Risk of Bias 1 tool. We performed descriptive analyses, logistic regressions, and subgroup meta-analyses. ResultsWe included 361 trials, of which 23.3% were prospectively registered. Registered trials had lower risk of bias (odds ratio [OR] 0.6; 95% confidence interval [CI] 0.5, 0.7) and higher reporting quality (OR 1.6; 95% CI 1.4, 1.8) than unregistered trials. Prospectively registered trials were more likely to have low risk of reporting bias (OR 2.7; 95% CI 1.2, 6.5) and higher quality of reporting (OR 1.3; 95% CI 1.1, 1.6) than retrospectively registered trials. Trial registration status was not associated with effect estimates. Among prospectively registered trials, 64.3% clearly defined primary outcome(s) in their registration, 58.3% had consistent sample sizes, and 22.6% had no evidence of selective outcome reporting. Trials that clearly defined primary outcome(s) were more likely to report larger effect estimates for pain intensity (mean difference −15.8; 95% CI −22.7, −8.9 vs −6.0; 95% CI −10.6, −1.5; Q = 6.7, P = .01), although the difference was small, the 95% CIs overlapped, and no difference was found for functional limitations. ConclusionA small proportion of trials in the CLBP field were registered prospectively and many presented registration inconsistencies. Registered trials tend to have lower risk of bias and higher quality of reporting. Policies are needed to improve prospective registration and registration consistency in the field. Plain Language SummaryProspective trial registration is the practice of documenting the planned methods of a randomized controlled trial on a publicly available online platform (ie, website) before enrolling participants. Medical journals require trialists to prospectively register their trials to encourage the conduct of high-quality research and reduce the chance of trialists changing their research plan to report only positive or significant results (known as selective outcome reporting). We investigated whether trialists within the chronic low back pain field were registering their trials, and whether they followed their registered research plan.We used data from a large systematic review of 456 trials that tested the effectiveness of exercise as a treatment for chronic low back pain. We assessed each trials' registration status and whether prospectively registered trials had inconsistencies between their registered research plan and their research conduct (eg, evidence of selective outcome reporting). We also looked at the association among trial registration with trials’ quality of reporting (ie, a marker of research transparency), risk of bias (ie, a marker of research quality), and the amount of low back pain improvement reported by the trials (ie, effect estimates).We found that less than 25% of trials were prospectively registered, and many had inconsistencies between their registered research plan and their research conduct. Overall, registered trials had lower risk of bias and higher quality of reporting. However, trial registration status and selective outcome reporting were not associated with effect estimates (the amount of back pain improvement reported by trials). Our findings highlight the need for trialists and journals to better follow trial registration guidelines and policies in the chronic low back pain field. Knowledge users should be cautious when consuming information from unregistered trials as they appear to be more likely to have quality concerns.

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.

Electromagnetic stimulation to reduce the hypertonia of the pelvic floor muscles and improve chronic pelvic pain in women.

The increased hypertonicity or activity of pelvic floor muscles can lead to chronic pelvic pain (CPP). It represents an aspecific and persistent pain with no apparent clinical reason, affecting an estimated 6% to 16% of women worldwide. This study aimed to evaluate with validated questionnaires the efficacy and the safeness of a new device that uses Top flat Magnetic Stimulation for the management of muscular hypertonia in women with CCP. All patients underwent 8 treatments with a non-invasive electromagnetic therapeutic device. The device produces a TOP Flat Magnetic Stimulation with a uniform profile so, the muscle work aims to reduce pain while also inhibiting muscle activity. The PISQ-12 questionnaire was used for the evaluation of improvements. Side effects were monitored. The PISQ-12 total mean score decreases from 29,2 (±3.3) to 17 (±2). Regarding the behavioural-emotive items (1-4), a decrease from 12 (±2) to 7 (±0.9) was visible. Physical items (5-9) decrease from 10,6 (±1.8) to 6 (±1.4) and the Partner Related items (10-12) from 6,6 (±1.6) to 3,9 (±0.4). Conclusions: The device we used in this research demonstrated to be a valid solution for the treatment of chronic pelvic pain in female patients.

Transcutaneous neurostimulation parameters for neuropathic radicular pain: Results from a two period crossover randomized trial

ObjectivesTranscutaneous neurostimulation (TENS) is commonly used in the treatment of chronic radicular pain, but without any consensus on the type of current to be delivered. The aim of this study was to compare the conventional high-frequency, low-intensity current called c-TENS with a mixed current called m-TENS, combining c-TENS with a low-frequency, high-intensity current. MethodsThis was a single-blind, two-period crossover randomized trial. Included patients had chronic (≥3months), neuropathic (dn4≥4) radicular pain of at least moderate intensity (Visual Analogic Scale [VAS]≥40mm [0–100mm]). Patients were randomized to receive either c-TENS or m-TENS first, then the other, and both during one month. The primary outcome was the level of radicular pain, measured by VAS at the end of each of the two period. ResultsSeventy-four patients were included (mean age: 51.9±13.5years, female proportion: 65.6%). The mean duration of radicular pain was 45.2±51months and the mean radicular intensity was 67±12.5/100mm. After one month of treatment, VAS decreased to 53.9±20.1mm under c-TENS and to 53.9±21.3 under m-TENS (NS). Thirteen patients (20.3%) had a VAS<40/100 with either c-TENS or m-TENS (NS). Tolerance was the same for the two modes. Twenty-nine patients (46%) designated c-TENS as the most effective mode, and 34 patients (54%) designated m-TENS. ConclusionThis study shows no difference in terms of efficacy or tolerance between c-TENS and m-TENS. There is no justification for preferring one of these two modes over the other for the treatment of chronic neuropathic radicular pain.

Antidepressants for pain management in adults with chronic pain: a network meta-analysis.

Chronic pain is common and costly. Antidepressants are prescribed to reduce pain. However, there has not been a network meta-analysis examining all antidepressants across all chronic pain conditions, so effectiveness and safety for most antidepressants for pain conditions remain unknown. To assess the efficacy and safety of antidepressants for chronic pain (except headache) in adults. Our primary outcomes were as follows: substantial pain relief (50%), pain intensity, mood and adverse events. Our secondary outcomes were as follows: moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change, serious adverse events and withdrawal. This was a systematic review with a network meta-analysis. We searched CENTRAL, MEDLINE, EMBASE, CINAHL, LILACS, AMED and PsycINFO databases for randomised controlled trials of antidepressants for chronic pain conditions up until 4 January 2022. The review was registered in PROSPERO (CRD42020171855), and the protocol was published in the Cochrane Library (https://doi.org/10.1002/14651858.CD014682). We analysed trials from all settings. We included trials in which participants had chronic pain, defined as longer than 3 months, from any condition excluding headache. We included all antidepressants. Our primary outcome was substantial pain relief, defined as a reduction ˃ 50%. We also measured pain intensity, mood and adverse events. Secondary measures included moderate pain relief (above 30% reduction), physical function, sleep, quality of life, Global Impression of Change, serious adverse events, and withdrawal from trial. We identified 176 studies with a total of 28,664 participants. Most studies were placebo-controlled (n = 83) and parallel armed (n = 141). The most common pain conditions examined were fibromyalgia (59 studies), neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of randomised controlled trials was 10 weeks. Most studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. Standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that for duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain. The evidence for antidepressants other than duloxetine is poor. For duloxetine, it is not clear whether the effect applies to groups with both pain and low mood, since these groups were excluded from trials. There is also insufficient evidence on long-term outcomes and on adverse effects. There is only reliable evidence for duloxetine in the treatment of chronic pain. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Data for all other antidepressants were of low certainty. However, the findings should not be read as an encouragement to prescribe antidepressants where other non-pharmacological intervention could be equally effective, especially in the absence of good evidence on side effects and safety. There is a need for large, methodologically sound trials testing the effectiveness of antidepressants for chronic pain. These trials should examine long-term outcomes (> 6 months) and include people with low mood. There should also be better reporting of adverse events, tolerance of drugs, and long-term compliance. This study is registered as PROSPERO CRD42020171855. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR128782) and is published in full in Health Technology Assessment; Vol. 28, No. 62. See the NIHR Funding and Awards website for further award information.

The Clinical Implications of Transdermal Baclofen in the Management of Mild-Moderate Neuropathic Pain

The pharmacotherapeutic management of chronic pain is a particular challenge for healthcare providers, as patients often require multimodal analgesia and polypharmacy in order to achieve symptomatic relief. Patient adherence, frequent dose titration, patient comorbidities, and individual characteristics can further complicate treatment and limit treatment options at the outpatient level. The therapeutic potential of localized analgesia in the treatment of chronic pain is of particular interest to healthcare providers nationwide, as it provides a necessary alternative to systemic analgesia. Compounding Pharmacies and FDA Outsourcing Facilities aid in this endeavor through endogenous compounding and manufacturing (respectively) of externally-applied pain formulations. This review summarizes the available clinical evidence supporting transdermal baclofen utilization in the symptomatic management of chronic musculoskeletal and/or neuropathic pain. The adjunctive treatment of pain from a localized perspective remains under-investigated, and the role of transdermal analgesics/antispasmodics in chronic pain management remains uncertain.

Hemoglobin α-derived peptides VD-hemopressin (α) and RVD-hemopressin (α) are involved in electroacupuncture inhibition of chronic pain.

Knee osteoarthritis (KOA) is a chronic degenerative bone metabolic disease that primarily affects older adults, leading to chronic pain and disability that affect patients' daily activities. Electroacupuncture (EA) is a commonly used method for the treatment of chronic pain in clinical practice. Previous studies indicate that the endocannabinoid system is involved in EA analgesia, but whether endocannabinopeptide VD-hemopressin (α) and RVD-hemopressin (α) derived from hemoglobin chains are involved in EA analgesia is unclear. RNA-seq technology was used to screen which genes involved in EA analgesia. The expression of hemoglobin α chain and 26S proteasome were determined by Western blotting. The level of VD-hemopressin (α) and RVD-hemopressin (α) were measured by UPLC-MS/MS. Microinjection VD-Hemopressin (α), RVD-Hemopressin (α) and 26S proteasome inhibitor MG-132 into vlPAG, then observe mechanical and thermal pain thresholds. Therefore, we used RNA-seq to obtain differentially expressed genes Hba-a1 and Hba-a2 involved in EA analgesia in the periaqueductal gray (PAG), which were translated into the hemoglobin α chain. EA significantly increased the expression of the hemoglobin α chain and the level of hemopressin (α) and RVD-hemopressin (α). Microinjection of VD-hemopressin (α) and RVD-hemopressin (α) into the ventrolateral periaqueductal gray (vlPAG) mimicked the analgesic effect of EA, while CB1 receptor antagonist AM251 reversed this effect. EA significantly increased the expression of 26S proteasome in KOA mice. Microinjection of 26S proteasome inhibitor MG132 before EA prevented both the anti-allodynic effect and upregulation of the concentration of RVD-hemopressin (α) by EA treatment and upregulated the expression of the hemoglobin α chain. Our data suggest that EA upregulated the concentration of VD-hemopressin (α) and RVD-hemopressin (α) through enhancement of the hemoglobin α chain degradation by 26S proteasome in the PAG, then activated the CB1 receptor, thereby exerting inhibition of chronic pain in a mouse model of KOA. These results provide new insights into the EA analgesic mechanisms and reveal possible targets for EA treatment of chronic pain.

Targeting the Main Sources of Reactive Oxygen Species Production: Possible Therapeutic Implications in Chronic Pain.

Humans have long been combating chronic pain. In clinical practice, opioids are firstchoice analgesics, but long-term use of these drugs can lead to serious adverse reactions. Finding new, safe and effective pain relievers that are useful treatments for chronic pain is an urgent medical need. Based on accumulating evidence from numerous studies, excess reactive oxygen species (ROS) contribute to the development and maintenance of chronic pain. Some antioxidants are potentially beneficial analgesics in the clinic, but ROS-dependent pathways are completely inhibited only by scavenging ROS directly targeting cellular or subcellular sites. Unfortunately, current antioxidant treatments do not achieve this effect. Furthermore, some antioxidants interfere with physiological redox signaling pathways and fail to reverse oxidative damage. Therefore, the key upstream processes and mechanisms of ROS production that lead to chronic pain in vivo must be identified to discover potential therapeutic targets related to the pathways that control ROS production in vivo. In this review, we summarize the sites and pathways involved in analgesia based on the three main mechanisms by which ROS are generated in vivo, discuss the preclinical evidence for the therapeutic potential of targeting these pathways in chronic pain, note the shortcomings of current research and highlight possible future research directions to provide new targets and evidence for the development of clinical analgesics.