Duloxetine Versus Placebo in Patients With Chronic Low Back Pain: A 12-Week,Fixed-Dose,Randomized, Double-Blind Trial

This randomized, double-blind, placebo-controlled study assessed efficacy and safety of duloxetine in patients with chronic low back pain (CLBP). Adults (n = 401) with a nonneuropathic CLBP and average pain intensity of ≥4 on an 11-point numerical scale (Brief Pain Inventory [BPI]) were treated with either duloxetine 60 mg once daily or placebo for 12 weeks. The primary measure was BPI average pain. Secondary endpoints included Patient's Global Impressions of Improvement (PGI-I), Roland Morris Disability Questionnaire (RMDQ-24), BPI-Severity (BPI-S), BPI-Interference (BPI-I), and response rates (either ≥30% or ≥50% BPI average pain reduction at endpoint). Health outcomes included Short Form-36, European Quality of Life–5 Dimensions, and the Work Productivity and Activity Impairment questionnaire. Safety and tolerability were assessed. Compared with placebo-treated patients, duloxetine-treated patients reported a significantly greater reduction in BPI average pain (P ≤ .001). Similarly, duloxetine-treated patients reported significantly greater improvements in PGI-I, BPI-S, BPI-I, 50% response rates, and some health outcomes. The RMDQ and 30% response rate showed numerical improvements with duloxetine treatment. Significantly more patients in the duloxetine group (15.2%) than patients in the placebo group (5.4%) discontinued because of adverse events (P = .002). Nausea and dry mouth were the most common treatment-emergent adverse events with rates significantly higher in duloxetine-treated patients.     

A Review of Duloxetine 60 mg Once‐Daily Dosing for the Management of Diabetic Peripheral Neuropathic Pain,Fibromyalgia, and Chronic Musculoskeletal Pain Due to Chronic Osteoarthritis Pain and Low Back Pain

Background: Duloxetine is a selective dual neuronal serotonin (5‐Hydroxytryptamine, 5‐HT) and norepinephrine reuptake inhibitor (SSNRI). It is indicated in the United States for treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), and several chronic pain conditions, including management of diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain due to chronic osteoarthritis (OA) pain and chronic low back pain (LBP). Its use for antidepressant and anxiolytic actions has been extensively reviewed previously. We here review the evidence for the efficacy of 60 mg once‐daily dosing of duloxetine for chronic pain conditions. Method: The literature was searched for clinical trials in humans conducted in the past 10 years involving duloxetine. Results: There were 199 results in the initial search. Studies not in the English language were excluded. We then included only studies of diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain (OA and LBP). Studies of painful symptoms reported in mental health studies were excluded. This resulted in 32 studies. Articles that did not include a 60 mg/day daily dose as a study arm were excluded. This resulted in 30 studies, broken down as follows: 12 for diabetic peripheral neuropathy, 9 for fibromyalgia, 6 for LBP, and 3 for OA pain. Conclusions: The studies reviewed report that duloxetine 60 mg once‐daily dosing is an effective option for the management of diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain due to chronic OA pain and chronic LBP. As these pains are often comorbid with MDD or GAD, duloxetine might possess the pharmacologic properties to be a versatile agent able to address several symptoms in these patients. With adequate attention to FDA prescribing guidance regarding safety and drug–drug interactions, duloxetine 60 mg once‐daily dosing appears to be an effective option in the appropriate pain patient population.     

A Double‐blind,Randomized, Placebo‐controlled Study of the Efficacy and Safety of Duloxetine for the Treatment of Chronic Pain Due to Osteoarthritis of the Knee

Objective: To evaluate the efficacy and safety of duloxetine in the treatment of chronic pain due to osteoarthritis of the knee. Methods: This was a 13‐week, randomized, double‐blind, placebo‐controlled trial in patients meeting American College of Rheumatology clinical and radiographic criteria for osteoarthritis of the knee. At baseline, patients were required to have a ≥ 4 weekly mean of the 24‐hour average pain ratings. Patients were randomized to either duloxetine 60 mg once daily (QD) or placebo. At week 7, the duloxetine dosage was increased, in a blinded fashion, to 120‐mg QD in patients reporting < 30% pain reduction. The primary efficacy measure was Brief Pain Inventory (BPI) 24‐hour average pain. Secondary efficacy measures included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); Clinical Global Impressions of Severity (CGI‐S). Safety and tolerability was also assessed. Results: Of the total (n = 256) patients, 111 (86.7%) in placebo group and 93 (72.7%) in duloxetine group completed the study. Patients treated with duloxetine had significantly (P ≤ 0.001) greater improvement at all time points on BPI average pain and had significantly greater improvement on BPI pain severity ratings (P ≤ 0.05), WOMAC total (P = 0.044) and physical functioning scores (P = 0.016), and CGI‐S (P = 0.009) at the study endpoint. Frequency of treatment‐emergent nausea, constipation, and hyperhidrosis were significantly higher in the duloxetine group (P ≤ 0.05). Significantly more duloxetine‐treated patients discontinued the trial because of adverse events (P = 0.002). Conclusions: Treatment with duloxetine 60 mg to 120 mg QD was associated with significant pain reduction and improved function in patients with pain due to osteoarthritis of the knee.     

Pain Neurophysiology Education and Therapeutic Exercise for Patients With Chronic Low Back Pain: A Single-Blind Randomized Controlled Trial

Objective

To assess the effect of a pain neurophysiology education (PNE) program plus therapeutic exercise (TE) for patients with chronic low back pain (CLBP).

Understanding Placebo and Nocebo Responses for Pain Management

Placebo analgesia makes individuals experience relief of their pain simply by virtue of the anticipation of a benefit. A reduction of pain can occur also when placebos follow the administration of active and effective painkillers. In fact, studies indicate that placebos mimic the action of active treatments and promote the endogenous release of opioids in both humans and animals. Finally, social support and observational learning also lead to analgesic effects. Thus, different psychological factors and situations induce expectations of analgesia facilitating the activation of the top-down systems for pain control along with the release of endogenous mediators crucially involved in placebo-induced benefits. Recent scientific investigation in the field of brain imaging is opening new avenues to understanding the cognitive mechanisms and neurobiological substrates of expectation-induced pain modulation. Gaining deeper knowledge of top-down mechanisms of pain modulation has enormous implications for personalizing and optimizing pain management.     

A Randomized,Single-Blind Study Evaluating the Effect of a Bone Pain Education Video on Reported Bone Pain in Patients with Breast Cancer Receiving Chemotherapy and Pegfilgrastim

Background: Mild-to-moderate bone pain is the most commonly reported adverse event associated with pegfilgrastim. Aims: To investigate the effect of bone pain education on pegfilgrastim-related bone pain in patients with breast cancer receiving chemotherapy and pegfilgrastim. Design: Randomized, single-blind study. Settings: Forty-eight community oncology clinics throughout the United States. Participants: Three hundred women ≥18 years of age with newly diagnosed stage I -III breast cancer, who were planning ≥4 cycles of neoadjuvant or adjuvant chemotherapy with pegfilgrastim support starting in cycle 1. Methods: Patients were randomized 1:1 to view a general education DVD on chemotherapy side effects (GE-DVD) or a DVD on bone pain following chemotherapy and pegfilgrastim (BP-DVD). Patients recorded severity of bone pain on a scale of 0-10, location of pain, and use of bone pain medications (i.e., analgesics, antihistamines, and nonsteroidal anti-inflammatory drugs) for 5 days, beginning on the day of pegfilgrastim administration, in each of the first four chemotherapy cycles. Results: Patient-reported maximum bone pain was similar in the two groups (GE-DVD vs BP-DVD: cycle 1, 3.2 vs. 3.5, p = .3479; across all cycles, 4.1 vs. 4.6, p = .2196). Other measures of bone pain were also similar between the groups. Bone pain was highest in cycle 1 but decreased and then remained stable in subsequent cycles. Bone pain medication use was similar in both groups and was highest in cycle 1. Conclusions: The bone pain-specific education evaluated here did not improve perceptions of bone pain reported in this patient population.     

Prospective, Randomized, Single-Blind, Sham Treatment-Controlled Study of the Safety and Efficacy of an Electromagnetic Field Device for the Treatment of Chronic Low Back Pain: A Pilot Study

Objectives: To evaluate the efficacy and safety of therapeutic electromagnetic fields (TEMF) on chronic low back pain. Secondary objectives included the investigation of the effects of TEMF on psychometric measures. Setting: Pain Research center in an Urban Academic Rehabilitation Facility. Design: Prospective, randomized, single‐blind, placebo (sham) treatment‐controlled design in which participants were evaluated over a 6‐week period. A total of 40 subjects were randomly assigned: 20 subjects to 15 milliTESLA (mT) treatment using a prototype electromagnetic field device and 20 to sham treatment. Interventions: After a 2‐week baseline period, eligible individuals were randomized to one of the treatment groups (sham or 15 mT) for six 30‐minute treatments over 2 weeks, then a 2‐week follow‐up period. Outcome Measures: The primary outcome measure was the self‐report of pain severity using a 100 mm visual analog scale collected using a twice daily McGill Pain Questionnaire—Short Form. Several secondary measures were assessed. Results: Both groups (15 mT and sham) improved over time (P < 0.05). Although groups were similar during the treatment period, treated subjects (TEMF of 15 mT) improved significantly over sham treatment during the 2‐week follow‐up period (20.5% reduction in pain; F_1,34 = 10.62, P = 0.003). There were no reported serious adverse events. Conclusions: This study demonstrates that TEMF may be an effective and safe modality for the treatment of chronic low back pain disorders. More studies are needed to test this hypothesis.     

骨关节炎痛:病理生理学、诊断与处理

<正>在全世界,20%的慢性疼痛与骨关节炎(OA)有关,越来越多流行病学资料显示OA与年龄和肥胖的相关性。多年以来,由于对骨关节炎的发痛机制和治疗存在误解,骨关节痛一直被忽视。目前,在这方面还存在需要解决的问题:比如用来评估骨关节炎痛的特定的调查问卷、有效的且安全的镇痛剂(特别针对老年患者)、替代治疗及术后痛的预防。骨关节炎的病理生理学疼痛是骨关节炎的主要症状,包括外周和中枢机制。骨关节炎痛被认为是一种典型的伤害性疼痛状态。临床医师期望将疼痛作为一项关节退化程度的预警信号。骨关节炎疼痛的发生始于游离神经末梢,这些末稍主要位于滑膜、骨膜和肌腱,不存在于软骨。伤害感受性信息包括神经介质和     

骨性关节炎痛的动物模型

<正>IASP关节痛文献资料,《中国疼痛医学杂志》组织翻译第三篇:动物模型,不仅帮助科学家们深入研究骨性关节炎(osteoarthritis,OA)的疼痛机制,并且为寻找新的治疗方法提供基础。然而,以往的OA模型,主要是用来反映结构病理学变化。直到最近,OA模型用于研究人类OA痛的有效性,才被详细的阐明。OA痛模型的不同,反应OA患者个体之间痛体验的差异。动物OA是逐渐发展形成的。例如,Dunkin-Hartley豚鼠、STR/ort小鼠、狗和马。然而,动物OA的发展过程很难预测的,且缺乏有效的控制措施。动物OA模型包括2大类:(1)手术模型:半月板和/或交叉韧带的横断术,或关     

Efficacy of Duloxetine in Patients with Chronic Pain Conditions

The primary objective of this study is to review the efficacy of duloxetine in treating chronic pain using the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations for clinical significance across chronic pain states. These include pain intensity, patient ratings of overall improvement, physical functioning, and mental functioning. This review comprised the side-by-side analyses of 12 double-blind, placebo-controlled trials of duloxetine in patients with chronic pain (diabetic peripheral neuropathic pain, fibromyalgia, chronic pain due to osteoarthritis, and chronic low back pain). Patients received duloxetine (60 to 120 mg/day) or placebo. Average pain reduction was assessed over 3 months as the primary efficacy outcome. Other measures used were physical function and Patient Global Impression of Improvement. In 10 of the 12 studies, statistically significant greater pain reduction was observed for duloxetine- compared with placebo-treated patients. The response rates based on average pain reduction, improvement of physical function, and global impression were comparable across all 4 chronic pain states. Compared with patients on placebo, significantly more patients treated with duloxetine reported a moderately important pain reduction (≥30% reduction) in 9 of the 12 studies, a minimally important improvement in physical function in 8 of the 12 studies, and a moderately important to substantial improvement in Patient Global Impression of Improvement rating in 11 of the 12 studies. The analyses reported here show that duloxetine is efficacious in treating chronic pain as demonstrated by significant improvement in pain intensity, physical functioning, and patient ratings of overall improvement.     

The Effect of Preoperative Intra-Articular Methylprednisolone on Pain After TKA: A Randomized Double-Blinded Placebo Controlled Trial in Patients With High-Pain Knee Osteoarthritis and Sensitization

In a randomized, double-blind, placebo controlled trial, we investigated the postoperative analgesic effect of a single intra-articular injection of 40?mg methylprednisolone acetate (MP) administered 1 week before total knee arthroplasty (TKA). Forty-eight patients with high pain osteoarthritis (≥5 on a numeric rating scale during walk) and sensitization (pressure pain threshold?<250?kPa), aged 50 to 80 years and scheduled for primary unilateral TKA under spinal anaesthesia were included. The primary outcome was the proportion of patients with moderate/severe pain during a 5-m walk test 24 hours postoperatively. Secondary outcomes included pain at 48 hours, during the first 14 days, sensitization (quantitative sensory testing with pressure pain threshold and wind-up from temporal summation), and inflammatory changes (systemic C-reactive protein, intra-articular interleukin [IL]-6). No difference in the proportion of patients with moderate/severe pain was found between MP/placebo groups at 24 hours (67% and 74%, χ²?=?.2, P?=?.63, odds ratio = .7, 95% confidence interval = .2–2.8) or at 48 hours (57% and 68%, χ²?=?.5, P?=?.46, odds ratio = .6, 95% confidence interval = .2–2.3), and no difference between groups in postoperative sensitization was found (P?>?.4) despite reduced preoperative intra-articular inflammation (IL-6) in the MP group versus placebo (median change in IL-6 = ?70?pg/mL, interquartile range = ?466 to 0 vs. 32?pg/mL, interquartile range = ?26 to 75, P = .029). Alternative central or peripheral analgesic interventions in this high-risk group are required.

A Functional Neuroimaging Study of Expectancy Effects on Pain Response in Patients With Knee Osteoarthritis

Placebo treatments and healing rituals share much in common, such as the effects of expectancy, and have been used since the beginning of human history to treat pain. Previous mechanistic neuroimaging studies investigating the effects of expectancy on placebo analgesia have used young, healthy volunteers. Using functional magnetic resonance imaging (fMRI), we aimed to investigate the neural mechanisms by which expectancy evokes analgesia in older adults living with a chronic pain disorder and determine whether there are interactions with active treatment. In this fMRI study, we investigated the brain networks underlying expectancy in participants with chronic pain due to knee osteoarthritis (OA) after verum (genuine) and sham electroacupuncture treatment before and after experiencing calibrated experimental heat pain using a well tested expectancy manipulation model. We found that expectancy significantly and similarly modulates the pain experience in knee OA patients in both verum (n?=?21, 11 female; mean?±?SD age 57?±?7 years) and sham (n?=?22, 15 female; mean?±?SD age 59?±?7 years) acupuncture treatment groups. However, there were different patterns of changes in fMRI indices of brain activity associated with verum and sham treatment modalities specifically in the lateral prefrontal cortex. We also found that continuous electroacupuncture in knee OA patients can evoke significant regional coherence decreases in pain associated brain regions. Our results suggest that expectancy modulates the experience of pain in knee OA patients but may work through different pathways depending on the treatment modality and, we speculate, on pathophysiological states of the participants.

Correlation Among Pain Intensity,Catastrophizing, and Falls in Older Individuals With Unilateral Knee Osteoarthritis: A Cross-Sectional Study

ObjectiveThe purpose of this study was to investigate whether pain intensity and catastrophizing are associated with fear of falls and the number of falls in older persons with knee osteoarthritis (OA).MethodsA cross-sectional study was conducted involving 100 volunteers (male and female participants), 60 to 80 years old, with a diagnosis of knee OA. Patients were recruited from a physical therapy clinic in the city of São Paulo, Brazil, from March 2019 to November 2019. The following measures were used for the evaluations: Numerical Rating Pain Scale (NRPS), Pain-Related Self-Statement Scale (PRSS), and Falls Efficacy Scale. In statistical analysis, histograms were created to determine the distribution of data. Spearman's correlation coefficients (r_s) were then calculated to determine the strength of the associations among the variables. The receiver operating characteristic curve was used to identify the accuracy of PRSS and NRPS in differentiating participants with a history of falls from those without.ResultsNo significant correlation was found among the pain intensity, pain catastrophizing, fear of falling, and number of falls (r_s value ranging from –0.033 to –0.167; P value ranging from .096-.743). The accuracy of PRSS and NRPS in differentiating participants with falls from those without was insufficient, with area under the curve values of 0.46 and 0.42, respectively.ConclusionPain catastrophizing and intensity were not significantly associated with fear of falling and numbers of falls in older individuals with unilateral knee OA.     

Duloxetine and Pregabalin for Pain Management in Multiple Rheumatic Diseases Associated with Fibromyalgia

The fibromyalgia syndrome (FMS) is characterized by chronic and widespread musculoskeletal pain and soreness accompanied by sleep disorders, chronic fatigue and affective disorders. FMS is often associated with other forms of immuno‐rheumatic diseases. Although FMS pathophysiology is still not fully understood, a number of neuroendocrine, neurotransmission and neurosensitive disorders might generate a mechanism for the elicitation of pain by “central sensitization,” which is common to many other painful conditions. The present case describes the success of a therapeutic scheme, which associates two different pharmacological classes, anticonvulsants and new‐generation antidepressants, when FMS complicates a rare pathology called Cogan's syndrome. The association of two drugs might noticeably affect the molecular mechanisms of difficult pain, thus solving painful conditions of multifactorial origin.     

A Randomized, Double-blind Controlled Study of Jet Lidocaine Compared to Jet Placebo for Pain Relief in Children Undergoing Needle Insertion in the Emergency Department

Objectives: The objectives were to determine whether pretreatment with needleless jet‐delivered lidocaine decreases self‐reported pain in children undergoing needle insertion in the emergency department (ED) and to explore whether pretreatment with a jet device decreases self‐reported pain in children undergoing needle insertion in the ED. Methods: This study examined needle insertion pain in children 5–18 years of age. In the first phase of this study, children received either pretreatment with jet‐delivered lidocaine (0.2 mL of buffered 1% lidocaine; n = 75) or pretreatment with jet‐delivered placebo (0.2 mL of preservative‐free normal saline; n = 75) 60 seconds before undergoing needle insertion. This phase of the study had a randomized, double‐blind, placebo‐controlled design. In the second phase, an unblinded, nonconcurrent, nonintervention control group (n = 47) was examined to describe any effect of using the jet device. Patients reported pain upon administration of the jet device and at needle insertion using a 100‐mm color analog scale (CAS). Patients also reported their satisfaction with this device. The physicians and nurses performing needle insertions were asked to rate their ability to visualize the vein and their satisfaction with the device. Results: The mean (±standard deviation [SD]) needle insertion pain score for jet lidocaine, 28 (±7) mm, was similar to the mean needle insertion pain score for jet placebo, 34 (±7) mm. The mean needle insertion pain score for both the jet lidocaine and the jet placebo groups were lower than the needle insertion pain scores for the no device group, 52 (±8) mm. The majority of patients receiving the jet device reported that they would request this device for future needle insertions. Providers’ ratings of their ability to visualize veins and the patient cooperation were similar in all three groups. Conclusions: Jet‐delivered lidocaine is no more effective than jet‐delivered placebo in providing local anesthesia for needle insertion. Jet lidocaine and jet placebo may provide superior analgesia compared to no local anesthetic pretreatment.     

Prior Pain Exposure and Mere Possession of a Placebo Analgesic Predict Placebo Analgesia: Findings From a Randomized,Double-Blinded,Controlled Trial

A recent study found that merely possessing a placebo analgesic reduces pain. The current study tested for a possible moderator of this effect. Specifically, does the mere possession of a placebo analgesic affect pain for individuals with and without immediate prior experience with the pain task? Healthy participants (N = 127) were randomized to prior pain (PP) condition or without prior pain (No-PP) condition. In the PP condition, participants first did a preliminary trial of a cold pressor test (CPT) to induce direct experience with this pain stimulus. Then they were randomized to possess an inert cream described as either an analgesic cream or an anti-itch cream (pain-irrelevant control object). Participants then completed the main CPT. In the No-PP condition, participants underwent identical procedures and randomization except that they did not do a preliminary CPT, thus having no immediate prior CPT pain experience. We found a significant prior pain experience and possession status interaction effect on placebo analgesia. Participants in the No-PP condition showed evidence of lower pain when they merely possessed an analgesic cream than an anti-itch cream. Such mere possession effect was not found in the PP condition. The impact of expectancy and emotion on the underlying process are discussed.PerspectiveThis article presents a novel finding that prior pain exposure and mere possession of a placebo analgesic predicted placebo analgesia. It offers a novel perspective on the time course of placebo effect. It provides practical implications on potential pain intervention for clinicians and paradigm design for researchers of placebo study.     

Racial-Ethnic Differences in Osteoarthritis Pain and Disability: A Meta-Analysis

Osteoarthritis (OA), a leading cause of disability and pain, affects 32.5 million Americans, producing tremendous economic burden. Although some findings suggest that racial/ethnic minorities experience increased OA pain severity, other studies have shown conflicting results. This meta-analysis examined differences in clinical pain severity between African Americans (AAs) and non-Hispanic whites with OA. Articles were initially identified between October 1 and 5, 2016, and updated May 30, 2018, using PubMed, Web of Science, PsycINFO, and the Cochrane Library Database. Eligibility included English-language peer-reviewed articles comparing clinical pain severity in adult black/AA and non-Hispanic white/Caucasian patients with OA. Nonduplicate article abstracts (N = 1,194) were screened by 4 reviewers, 224 articles underwent full-text review, and 61 articles reported effect sizes of pain severity stratified by race. Forest plots of the standard mean difference showed higher pain severity in AAs for studies using the Western Ontario and McMasters Universities Osteoarthritis Index (0.57; 95% confidence interval [CI], 0.54–0.61) and non-Western Ontario and McMasters Universities Osteoarthritis Index studies (0.35, 95% CI, 0.23–0.47). AAs also showed higher self-reported disability (0.38, 95% CI, 0.22–0.54) and poorer performance testing (-0.58, 95% CI, -0.72 to -0.44). Clinical pain severity and disability in OA is higher among AAs and future studies should explore the reasons for these differences to improve pain management.PerspectiveThis meta-analysis shows that differences exist in clinical pain severity, functional limitations, and poor performance between AAs and non-Hispanic whites with OA. This research may lead to a better understanding of racial/ethnic differences in OA-related pain.