Severe Chronic Low Back Pain Research Articles

Prevalence of Acute Low Back Pain after Cesarean Delivery in Health Care Centers

Background: Low back pain is the common problem faced by mothers after cesarean delivery under spinal anesthesia. Application of spinal anesthesia leads to severe acute and chronic low back pain post-delivery. Physiotherapy plays an important role during and after pregnancy as it helps in reducing the incidence of low back pain and others musculoskeletal pain post-delivery. The aim of the study was to determine the prevalence of acute low back pain after cesarean section and to assess the percentage of population aware about antenatal and postnatal physiotherapy and percentages had taken the treatment in Heath care centers. Materials and methods: Study population comprised of 162 caesarean delivery females out of which 104 were selected of age between 19 to 35 having acute low back pain in postnatal cesarean ward of Heath care centers. Population was chosen through convenient sampling. Data collection tools were modified questionnaire. The data collected was analyzed through SPSS software Version 29.0.2.0(20). Prevalence and awareness were measured through descriptive statistics. Result: 64.1% postpartum caesarean section females had low back pain under spinal anesthesia.18.2% had mild pain,34.6% had moderate pain,30.7% had severe pain and 16.4% had very severe pain. Only18.3% were aware of antenatal and postnatal physiotherapy out of which only 6.7% had taken treatment.81.7% were unaware and 93.3% had not taken physiotherapy treatment. Low back pain is dependent upon Occupation and daily activity of the patient, awareness about antenatal and postnatal treatment is dependent upon educational level and patient age is seen as an associative factor for the patient dependency. Conclusion: Majority of postpartum caesarean delivery females complained of acute low back pain and very less had taken physiotherapy treatment during and after delivery. The majority were unaware about the antenatal and postnatal physiotherapy as they were not recommended by the gynecologist doctors. KEYWORDS: Acute back pain, Caesarean delivery, Spinal anesthesia, Antenatal, Postnatal, Physiotherapy, Awareness.

Evaluation of the efficacy, in terms of pain and disability, of a functional restoration programme in patients with chronic low back pain according to the presence of Modic 1 discopathy.

Modic type 1 disc disease (MD1) appears to be related to severe Chronic Low Back Pain (CLBP). Functional Restoration Programmes (FRP) recommended in CLBP may not be suitable for patients with MD1. The main objective was to evaluate the effectiveness of a FRP, on the perceived incapacity and the pain intensity, in patients with non-specific CLBP according to the presence of MD1. We performed a single-centre retrospective cohort study in which 271 patients were included. After one month in the FRP, this programme was considered "successful" if the pain visual analog scale had decreased by at least 20/100 millimetres and if the score of the French version of the Roland-Morris disability questionnaire had decreased by at least 4/24 points. The 271 patients had an average age of 43.2 (8.0) years and 58.3% were women. Out of our entire population, 128 (47.2%) patients were considered successful, and 51 (18.8%) patients had MD1. In patients without MD1, there was 49.1% success while this rate was 39.2% in those with MD1, but this difference was not statistically significant. We found no significant difference in the combination of pain and perceived disability after one month of a FRP in patients with CLBP without MD1 compared to those with CLBP with MD1. It therefore seems legitimate to offer FRP-type rehabilitation in patients with non-specific CLBP with MD1.

An Open-Label, Randomized, Parallel-Group Study to Assess the Safety, Efficacy, and Tolerability of Tapentadol Versus Tramadol in Outpatients with Moderate to Severe Chronic Low Back Pain at a Tertiary Care Hospital in South India

Low back pain is a very common musculoskeletal symptom with multifactorial aetiology. Aims and objectives: Our study aimed at comparing the efficacy, safety, and tolerability of tapentadol versus tramadol in out-patients with moderate to severe chronic low back pain. Fifty-two patients with a diagnosis of chronic low back pain for > 3 months were randomly assigned to receive either a 50 mg tablet of tapentadol (twice daily) or 50 mg tablet of tramadol (twice daily) for 1 week. The mean (±SD) difference in the reduction of pain (at end of 1 week) between the two groups was compared employing an independent student t-test for difference in mean values separately for the Visual Analogue Scale (VAS) and Roland Morris Disability Questionnaire (RMDQ) scores. The frequency of the different adverse events between the two groups was compared employing Chi-square test. Except for VAS scores, the baseline demographic parameters of the two groups were comparable. The study found that tapentadol reduced VAS and RMDQ scores more than tramadol (statistically significant p<0.001) between baseline and the end of week 1. Regarding safety and tolerability, the tapentadol group experienced nausea/vomiting and dizziness/somnolence more frequently than the tramadol group, with p-values of 0.011 and 0.001 respectively. Both groups experienced similar rates of headache and constipation, with p-values of 0.668 and 0.610, respectively. When compared to tramadol (50 mg twice daily), tapentadol (50mg twice daily) was found to significantly improve pain and disability in patients with moderate to severe chronic low back pain, while tapentadol had greater frequencies of side effects like nausea, vomiting, dizziness, and somnolence.

Restorative neurostimulation for chronic mechanical low back pain - Three year results from the United Kingdom post market clinical follow-up registry.

Mechanical chronic low back pain is often associated with impaired neuromuscular control of the lumbar multifidus muscles, the most important stabilizers of the lumbar spine. Restorative neurostimulation is a modality for the treatment for this specific subset of patients aimed to facilitate restoration of neuromuscular control by bilateral stimulation of the L2 medial branches. Evidence from both prospective and randomised clinical trials to date has demonstrated substantial improvements in clinical outcomes such as pain, disability and health-related quality of life. This study is an open label prospective follow-up for the treatment of chronic mechanical low back pain of nociceptive origin with restorative neurostimulation. Patients completed assessments for pain, disability and health-related quality of life. Outcomes were collected at 45, 90 and 180days, and 1, 2 and 3years after the activation visit. Forty-two patients were implanted with the device and 33 (79%) were available at the 3-year appointment. Patients in this cohort presented with severe chronic low back pain (NRS = 7.0 ± 0.2) and severe disability (ODI 46.6 ± 12.0). The health-related quality of life was also severely impacted at baseline (EQ-5D 0.426 ± 0.061). Changes in pain, disability and quality of life at three-year follow-up demonstrated a statistically significant improvement between baseline and 1, 2 and 3years. After 3years of therapy, average NRS scores had reduced to 2.7± 0.3 and mean ODI score to 26.0 ± 3.1 while EQ-5D-5L index improved to 0.707 ± 0.036. The ongoing follow-up of this post market cohort continues to demonstrate that restorative neurostimulation provides a statistically significant, clinically meaningful and durable response across pain, disability and quality-of life scores for patients suffering chronic mechanical low back pain that has been refractory to conventional management. ClinicalTrials.gov Identifier: NCT01985230.

ASSOCIATION OF CHRONIC LOW BACK PAIN AND DEPRESSION AT A TERTIARY CARE SETTING OF PAKISTAN

Objective: To assess the association of Depression with Chronic Low back pain. Methodology: In this cross-sectional investigation, 169 participants with a mean age of 54.1 years were studied at the PN Shifa medical outpatient department in Karachi, Pakistan. The research was conducted over a three-month period, from June to August 2020, using a non-probability convenience sampling approach. The severity of low back pain (LBP) was measured using the Numeric Rating Scale (NRS) and the Wong Baker Faces Pain Rating Scale. To evaluate levels of depression, the Patient Health Questionnaire (PHQ-9) scale was employed. The Chi-square test and one-way ANOVA test were used to establish statistical significance. Results: Patients with moderate to severe chronic low back pain (CLBP) demonstrated higher pain levels on both the Wong Baker Faces Pain Rating Scale and NRS, with a p-value of 0.000. Based on the PHQ-9 scores, severe depression correlated with more intense pain, with a p-value of 0.000, and greater pain severity in the current and previous week (as assessed by the NRS and Wong Baker Faces Pain Rating Scale). A higher percentage of males (34%) experienced mild CLBP compared to females (22%). However, 26% of females were found to suffer from severe CLBP, as opposed to 12% of males, with a p-value of 0.014. Conclusion: Patients with chronic low back pain often experience depression and report high levels of pain.

Successful use of differential target multiplexed spinal cord stimulation for chronic postsurgical abdominal pain

Recent advances in stimulation techniques have improved the efficacy and expanded the applicability of spinal cord stimulation (SCS). Among these techniques, there are no reports on the efficacy of differential target multiplexed (DTM) SCS for chronic postsurgical pain (CPSP) after abdominal surgery. Therefore, we present the successful use of DTM SCS for CPSP after distal pancreatectomy. A 49-year-old man with hypertension and severe chronic low back pain presented with neuropathic CPSP involving the left abdomen in the area of a laparotomy incision. His pain was refractory to conservative treatment and was rated 10 on a numerical rating scale (NRS). He underwent permanent implantation of a pulse generator after a 14-day trial stimulation. Chronic postsurgical pain was well controlled (NRS 1-2) at a 3-month follow-up with DTM SCS. Differential target multiplexed SCS can be a new treatment option for neuropathic CPSP that is resistant to conservative treatment. It is important to further examine the characteristics of CPSP and identify appropriate candidates for the successful use of DTM SCS.

Management of chronic low back pain and the impact on patients' personal and professional lives: Results from an international patient survey.

ObjectiveThe objective of this study was to investigate the impact of chronic low back pain (CLBP) on patients’ personal and professional lives, and management strategies applied to treat CLBP.MethodsA 60‐question survey was developed, and respondents from 16 countries with a self‐reported physician's diagnosis of CLBP were recruited via an online market research survey panel. Respondents were stratified as having mild, moderate, or severe pain. Target sample sizes per country and for pain severity were set. Data were weighted according to the known population and prevalence of CLBP in each country and the number of respondents from that country.ResultsResults from 9642 CLBP patients indicated that almost a quarter of patients with severe CLBP report a psychological comorbidity. Prescription pain medications were more commonly used by patients with severe CLBP (56%) than those with mild (20%) or moderate (34%) CLBP. Among those with severe CLBP who had been prescribed pain medication, 58% were prescribed opioids, with 1 in 4 patients using opioids for more than 5 years. Patients were primarily managed by general practitioners/primary care physicians, physiotherapists, neurologists, or orthopedic surgeons. CLBP negatively impacted patients’ daily activities, social lives, and work productivity.ConclusionChronic low back pain has pronounced effects on patients’ personal relationships, ability to work, and daily living. Almost 1 in four patients with severe CLBP reported a psychological comorbidity. Adherence to guidelines appears inconsistent, which is noteworthy as a substantial subgroup of patients with severe CLBP had been prescribed opioid medication for more than 5 years. Improved education is required to support healthcare professionals (HCPs) in identifying and understanding the complex biopsychosocial needs of CLBP patients to optimize pain management and to encourage referral of CLBP patients to physiotherapists and psychologists.

Anxiety sensitivity and fatigue severity among adults with chronic low back pain

ABSTRACT Background The combined impact of chronic low back pain (CLBP) and fatigue severity is associated with increased burden and worsened symptoms. Understanding factors that may contribute to and maintain fatigue severity among individuals with CLBP is needed to isolate intervention modalities. Methods The current study sought to investigate the role of anxiety sensitivity (AS) in terms of fatigue severity among 1,663 adults (70.0% female, Mage = 44.5 years, SD = 11.87) with current mild to severe CLBP as well as a subset of the sample with clinically significant fatigue (n = 778). Results Results indicated AS was a positively and statistically significant predictor of fatigue severity among the entire sample and the subset of the sample with clinically significant fatigue. Conclusions These cross-sectional data highlight the potential promise of AS as an underrecognized cognitive vulnerability for greater fatigue severity among those with CLBP.

Tapentadolprolonged release in patients with chronic low back pain: real-world data from the German Pain eRegistry.

Aim: Comparison of tapentadolprolonged release (PR) with other oral WHO-III PR opioid analgesics (morphine, oxycodone±naloxone, hydromorphone) in routine medical care of chronic low back pain. Patients & methods: Noninterventional, retrospective 12-week study usinganonymized clinical practice data from the German Pain eRegistry. Six effectiveness, tolerability, and safety criteria were aggregated in a primary composite end point (treatment responder). Propensity scoring matched 2331 datasets per treatment cohort. Results: All six single criteria showed significantly better outcomes for tapentadol PR (all parameters p<0.001). There were significantly more treatment responders under tapentadol PR (65.7 vs 14.2%; p<0.001). Conclusion: Tapentadol PR showed significantly better effectiveness and tolerability in severe chronic low back pain unsuccessfully treated with WHO-I/II analgesics compared with the other oral WHO-III PR opioids investigated.

Fatigue severity among adults with chronic low back pain: relations to opioid use and hazardous alcohol use

ABSTRACT Background : Chronic low back pain is the second leading cause of disability in the United States and is related to greater risk of opioid misuse. Research suggests that severe fatigue may be a relevant factor for better understanding the greater rates of opioid and misuse among adults with chronic low back pain. Therefore, the current study sought to examine differences in opioid misuse, risk for opioid use disorder, and hazardous alcohol use in two different groups: one group with clinically significant fatigue, and one group without clinically significant fatigue. Methods : Participants were recruited utilizing a validated online survey management system that yielded 1,681 adults (70.0% female, 81.1% White, Mage = 44.5 years, SD = 11.88) with current mild to severe chronic low back pain. One-way analysis of covariance (ANCOVA) models were conducted to examine group differences. Results : Among adults with chronic low back pain, those with clinically significant fatigue reported significantly greater opioid misuse and risk for opioid use disorder compared to those without clinically significant fatigue. These results were evident after controlling for pain severity and interference. The results for hazardous alcohol use were not significantly different between groups. Conclusions : Clinically significant fatigue is a distinguishing characteristic among adults with chronic low back pain in terms of opioid misuse and risk for opioid use disorder. Potential clinical implications of such findings suggest that it may be important for clinicians to assess fatigue levels to better manage opioid misuse potential among adults with chronic low back pain.

Severe chronic low back pain: patient journey from onset of symptoms to strong opioid treatments in Europe.

Aim: We report the first patient roadmap in severe chronic low back pain (cLBP) in Europe, assessing the views of cLBP patients and general practitioners (GPs) who treat cLBP with regard to current cLBP management. Methodology: Patient journey mapping was conducted in four European countries to assess the views of cLBP patients (n=20) and GPs (n=40). Results: Four broad phases of cLBP, subdivided into eight individual steps, were identified as part of the patient journey, showing a disconnect between patients' and physicians' treatment goals, and expectations regarding pain relief levels for some patients. Conclusion: Improved communication, with greater involvement of patients in multimodal management decisions, might benefit the GP-patient relationship and overall outcomes for cLBP patients.

Long-Term Effectiveness and Tolerability of Pain Treatment with Tapentadol Prolonged Release

BACKGROUND: The central analgesic tapentadol prolonged release (PR) has proven effective and generally well tolerated in a broad range of chronic pain conditions. Long-term data of its use are still scarce. OBJECTIVES: To evaluate long-term effectiveness, tolerability, and safety of tapentadol PR in patients with severe chronic osteoarthritis (OA) knee pain or low back pain (LBP) who responded to tapentadol in 1 of 4 preceding 12-week phase 3b clinical trials. STUDY DESIGN: Open-label, uncontrolled, observational extension study of up to 72 weeks. SETTING: Fourteen centers in Spain. Protocol approval by the reference ethics committee for all the participating centers. METHODS: Eligible patients started the extension trial on the tapentadol PR dosage optimized for them in the preceding trial; dose adjustments were permitted throughout the extension. Treatment effectiveness outcomes included changes in pain intensity, sleep, state of health, quality of life, patient and clinician global impression of change, and patients’ satisfaction with treatment. Patients with OA knee pain also answered the Western Ontario and McMaster Universities OA index, and patients with LBP with a possible neuropathic pain component completed neuropathic pain-related questionnaires. RESULTS: Eighty-three patients were enrolled: 40 with OA knee pain, 43 with LBP. The full analysis set consisted of 81 patients. Mean pain intensity remained relatively stable over the 72-week extension period with mean increases from baseline of 0.44 (95% confidence interval [CI], -0.1,1.0; Numeric Rating Scale) for all patients, 0.2 (95% CI, -0.5, 0.9) for patients with OA, and 0.68 (95% CI, -0.2, 1.6) for patients with LBP. State of health and quality of life baseline ratings were maintained; overall impression of change was “improved.” Most patients (88.9%) reported at least good treatment satisfaction at the end of treatment. Mean daily tapentadol PR doses slightly increased from 313.3 ± 139.5 mg at baseline to 315.7 ± 140.1 mg at end of study. Uptitration was required for 8.4% of the patients, 4.8% had a dose reduction during the trial. Adverse events considered probably/likely or certainly related to tapentadol PR treatment by the investigator were documented for 18.1% of all patients, most commonly constipation (7.2%). Seven patients (8.4%) experienced adverse events leading to premature discontinuation. LIMITATIONS: An open-label design, stable concomitant analgesics (World Health Organization step I), and dose adjustments were allowed during the study. All patients had benefitted from tapentadol PR in preceding trials. CONCLUSIONS: Sustained pain relief and quality of life for up to 72 treatment weeks under relatively stable dosing, as well as the good safety profile, indicate the usefulness of tapentadol PR for patients who suffer from severe chronic OA knee pain and LBP with limited risk for tolerance development. KEY WORDS: Tapentadol prolonged release, extension study, long-term, chronic pain, osteoarthritis, low back pain, efficacy, safety

Physical Performance, Anthropometrics and Functional Characteristics Influence the Intensity of Nonspecific Chronic Low Back Pain in Military Police Officers.

Background: Chronic low back pain (CLBP) is a serious problem in Military Police Officers (MPO), which accounts for up to 45% of the sick leave rates. It has been assumed that the strength and the endurance of trunk flexor and extensor muscles are CLPB key factors, but it is not known whether these attributes are related to pain intensity. It was aimed to determine whether the strength and endurance of trunk flexor and extensor muscles differ in MPO with no pain (CON; n = 24), moderate (MOD; n = 42), and severe (SEV; n = 37) nonspecific chronic low back pain (CLBP). Methods: The peak torque and endurance test of trunk flexor (PTF.BM−1) and extensor (PTE.BM−1) muscles were compared. A multiple regression analysis was used to identify pain intensity predictors in all groups (PAIN) and according to pain intensity (MOD and SEV). Results: The PTF.BM−1 was negatively related to pain and was a significant predictor, irrespective of pain intensity (PAIN). Conclusion: When pain intensity was considered the PTF.BM−1 and PTE.BM−1 explained the pain in the MOD, while the PTE.BM−1 and service time explained pain intensity in the SEV. Endurance of the flexor and extensor muscles was not related to pain intensity. These results indicated that training protocols must emphasize specific strengthening routines.

Fatigue severity and fatigue sensitivity: relations to anxiety, depression, pain catastrophizing, and pain severity among adults with severe fatigue and chronic low back pain

Chronic low back pain is the second leading cause of disability in the United States, and it is often associated with severe fatigue. However, little is known about individual differences that may be related to poorer mental health and pain among individuals with severe fatigue and chronic low back pain. The aim of the current investigation was to explore the role of fatigue severity and fatigue sensitivity in terms of anxiety and depressive symptoms, pain catastrophizing, pain interference, and pain severity among 783 adults with severe fatigue and chronic low back pain. Results suggest that fatigue severity and fatigue sensitivity were statistically significant predictors for anxiety, depression, pain interference, and pain catastrophizing. However, only fatigue sensitivity significantly predicted pain severity. Overall, the current study provides initial support for the role of fatigue severity and fatigue sensitivity in the presence of mental and physical health complaints among individuals with severe fatigue and chronic low back pain.

Efficacy and tolerability of tapentadol for the treatment of chronic low back pain in elderly patients.

Chronic low back pain (CLBP) is a highly prevalent and disabling condition in the elderly, and yet it is undertreated and understudied in this patient population. Tapentadol is a central analgesic with an improved tolerability profile that may be particularly beneficial to the elderly CLBP. We performed an observational retrospective study to comparatively assess the efficacy and tolerability of tapentadol in young and elderly patients with severe CLBP. Sixtyfive young patients (< 65years) and 87 elderly patients (≥ 65years) were titrated on tapentadol extended release to their optimal dose (25-250mg bid) over 1month and, then, maintained at that dose for 3months. The primary endpoint werechanges from baseline in 24-h pain intensity on a 0-10 Numerical Rating Scale (NRS) at month-4 of treatment (titration plus maintenance periods). Patients were assessed for several efficacy and tolerability outcomes using a battery of scales and tests for neuropathic pain intensity, quality of life and sleep, and cognitive and gastrointestinal functions. At pretreatment, young and elderly patients had similar pain intensities with younger patients presenting with more intense depressive and neuropathic pain symptoms, and lesser comorbidities and durations of pain (P < 0.05). Thirty-eight patients discontinued treatment because of adverse events occurring mostly during titration. Treatment with tapentadol was associated with comparable and clinically meaningful pain reductions in 24-h NRS from baseline to treatment month-4 both in young and elderly patients (-5.3 ± 1.4 and -4.8 ± 2.1; P < 0.01); a 50% pain relief was achieved in 66% and 58% of young and elderly patients. The percentage of patients with a neuropathic component decreased similarly in young and elderly patients (from38to0% and from19to3%; P < 0.01). Quality of life and sleep improved. The performances in global cognition and sustained attention tasks remained stable or improved across all age group. These findings indicate that tapentadol extended release maintains efficacy and good tolerability in CLBP patients with advancing age.

Measuring Opioid Withdrawal in a Phase 3 Study of a New Analgesic, NKTR-181 (Oxycodegol), in Patients with Moderate to Severe Chronic Low Back Pain

ObjectiveTo evaluate the SUMMIT-07 trial opioid withdrawal results of NKTR-181 (oxycodegol), a new molecular entity mu-opioid receptor agonist.DesignPhase 3, enriched-enrollment, double-blind, randomized-withdrawal study in patients with chronic low back pain (CLBP).SettingConducted in the United States at multiple sites.MethodsSUMMIT-07 was comprised of five periods: screening; NKTR-181 open-label titration (100 to 400 mg twice daily); 12-week randomized, double-blind study drug (NKTR-181 or placebo); one-week study drug taper; and two-week safety follow-up. Permitted rescue medication included hydrocodone 5 mg/acetaminophen 300 mg (two tablets daily) for two weeks after randomization, then acetaminophen 1.0 gm daily for the remainder of the trial. Signs and symptoms of drug withdrawal were evaluated using the Clinical Opiate Withdrawal Scale (COWS); Subjective Opiate Withdrawal Scale (SOWS); Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS); and withdrawal-related adverse events.ResultsOf 1,190 patients entering titration, one patient had moderate withdrawal (COWS score 13/48 maximum) three days after discontinuing NKTR-181. Of 610 patients randomized (N = 309, NKTR-181; N = 301, placebo), no COWS scores indicating withdrawal at a moderate level or greater (i.e., score ≥13) were observed at any time point. At day 8 after randomization, week 12, and the end of tapering, COWS scores indicating mild withdrawal (<13) were observed in seven (2.4%), one (0.4%), and one (0.5%) placebo patients, respectively, and three (1.0%), one (0.4%), and five (2.3%) NKTR-181 patients, respectively. Mean SOWS scores in both arms were ≤2.8 of 64 possible points at all time points. During the randomized period, of 35 events identified by MADDERS, adjudicators identified 20 possible “withdrawal” events (9 [2.9%] NKTR-181 and 11 [3.7%] placebo).ConclusionsNKTR-181 exhibited a low rate and severity of opioid withdrawal in SUMMIT-07 patients with CLBP.

Perception of verticality is altered in people with severe chronic low back pain compared to healthy controls: A cross-sectional study

BackgroundPeople with chronic low back pain (CLBP) have abnormal lumbar proprioception, which increases their reliance on visual input to maintain body verticality. Maintaining verticality is important for spatial orientation, balance and movement coordination. It is unknown if these patients also have altered perception of verticality. ObjectiveTo compare whether the perception of verticality is different between people with and without CLBP. DesignCross-sectional. MethodsTwo comparisons of perception of verticality were done between a group of people with CLBP (n = 25) and healthy people (n = 25); and between a subgroup of people with severe CLBP (n = 14) and healthy people (n = 25). In a dark room, the subjective visual vertical test was performed under 3 conditions: rod, rod-and-frame, and rod-and-disc. In each condition, the rod was tilted 40° clockwise and counterclockwise, and the participants were asked to bring it back to vertical 0° position. The rod deviation from verticality was recorded in degrees. ResultsWhen considering the CLBP group, analysis of variance showed that deviation from verticality had no significant group interaction with condition (p = 0.2), or group main effect (p = 0.2). However, deviation from verticality was significantly different between the conditions (p < 0.001). When considering the severe CLBP subgroup, the interaction effect was significant (p = 0.046). Simple main effects showed that the severe CLBP subgroup had larger deviations from verticality (7.5 ± 0.9 deg) compared to the healthy group (4.2 ± 0.7 deg) specifically on the rod-and-frame condition (p = 0.007). ConclusionPeople with severe CLBP appear to have larger deviations in judging verticality compared to the healthy group.

A Novel Algorithm to Identify Predictors of Treatment Response: Tapentadol Monotherapy or Tapentadol/Pregabalin Combination Therapy in Chronic Low Back Pain?

Purpose: High dose monotherapies or drug combinations are used to achieve sufficient analgesia for the treatment of severe chronic low back pain, before invasive therapy options are considered. In order to demonstrate an alternative for an empirical treatment approach, the authors' primary aim was to present an algorithm for the objective identification of treatment predictors. Additionally, the study identified baseline-characteristics in chronic low back pain patients prior to tapentadol PR treatment, as well as scrutinized those patients, either benefitting from a medium/high dose tapentadol PR monotherapy or a combination therapy (medium dose tapentadol PR + pregabalin).Patients and Methods: The statistical approach included data of a previously published randomized, double blind, phase 3b study which compared the effectiveness and safety of tapentadol PR vs. a combination of tapentadol PR and pregabalin. In total, 46 clinical parameters were included in the statistical prediction models which were applied separately either to 50 patients who already responded well during the titration period (i.e., medium dose tapentadol PR) or to 261 patients with in the comparative treatment period [i.e., monotherapy (high dose tapentadol PR) or combination therapy (medium dose tapentadol PR/pregabalin)].Results: The first statistical model identified three co-variables (NRS-3, PDQ, SQ) with predictive effects on patients responding well (“optimal responders”) to a medium dose tapentadol PR titration. Those patients presented low baseline pain intensity scores, good sleep quality and high painDETECT scores. The second statistical model identified eight co-variables (PDQ, numbness, SF-12 MCS, SF-12 PCS, VAS, HADS-A, HADS-D, SQ) with predictive effects on patients responding to high dose tapentadol PR monotherapy vs. a combination therapy (tapentadol PR + pregabalin). The high dose tapentadol PR responders indicated high painDETECT scores, little numbness and a good mental health status. Whereas, the combination therapy (tapentadol PR + pregabalin) responders were characterized by severe sleep disturbances and little anxiety.Conclusion: The statistical analysis characterized chronic low back pain patients and identified factors contributing to a treatment response. Thus, this retrospective statistical algorithm represents an elegant method, which may contribute to future strategies toward a more individualized and improved mechanism based pain therapy.

Long-term Safety and Tolerability of NKTR-181 in Patients with Moderate to Severe Chronic Low Back Pain or Chronic Noncancer Pain: A Phase 3 Multicenter, Open-Label, 52-Week Study (SUMMIT-08 LTS).

ObjectiveTo evaluate the long-term safety of NKTR-181, a novel mu-opioid receptor agonist that may have reduced human abuse potential, in patients with moderate to severe chronic low back pain (CLBP) or other chronic noncancer pain (CNP).DesignUncontrolled, multicenter, open-label, long-term study of NKTR-181 comprised of three periods: screening (≤21 days), treatment (52 weeks), and safety follow-up (∼14 days after the last dose of NKTR-181).SettingMulticenter, long-term clinical research study.MethodsNKTR-181 administered at doses of 100–600 mg twice daily (BID) was evaluated in opioid-naïve and opioid-experienced patients. Patients were enrolled de novo or following completion of the randomized, placebo-controlled phase 3 efficacy study (SUMMIT-07). Safety assessments included adverse event documentation, measurements of opioid withdrawal, and clinical laboratory tests. Effectiveness was assessed using the modified Brief Pain Inventory Short Form (mBPI-SF).ResultsThe study enrolled 638 patients. The most frequently reported treatment-emergent adverse events (TEAEs) were constipation (26%) and nausea (12%). Serious TEAEs, reported in 5% of patients, were deemed by investigators to be unrelated to NKTR-181. There were no deaths or reported cases of respiratory depression. A sustained reduction in mBPI-SF pain intensity and pain interference from baseline to study termination was observed throughout treatment. Only 2% of patients discontinued NKTR-181 due to lack of efficacy, and 11% discontinued due to treatment-related AEs. NKTR-181 doses of up to 600 mg BID were generally well tolerated, and patients experienced low rates of opioid-related adverse events.ConclusionsThe study results support the premise that NKTR-181 is a safe and effective option for patients with moderate to severe CLBP or CNP.

Tapentadol Extended Release in the Treatment of Severe Chronic Low Back Pain and Osteoarthritis Pain.

Tapentadol is a novel pain reliever with apparently synergistic dual mechanisms of action, capable of addressing both nociceptive and neuropathic components of chronic pain. As an effective analgesic with good tolerability, tapentadol may be appropriate for patients suffering from severe chronic pain associated with low back pain (LBP) or osteoarthritis (OA). Efficacy studies of tapentadol in populations of patients with severe chronic LBP or OA pain suggest that tapentadol is non-inferior to oxycodone. Its tolerability, especially with respect to gastrointestinal (GI) side effects, may be better than that of other strong opioids in clinical trials and analyses of multiple trials. Patient satisfaction with tapentadol extended release for chronic noncancer pain syndromes is good. Although tapentadol has an opioid component with abuse liability, it appears to be a difficult opioid for tampering with less appeal to abusers than other opioids. For patients with severe LBP and OA pain, tapentadol appears to hold promise as a safe, effective therapeutic option.