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Objective VVZ-149 is a small molecule that both inhibits the glycine transporter type 2 and the serotonin receptor 5 hydroxytryptamine 2 A. In a randomized, parallel-group, and double-blind trial (NCT02844725), we investigated the analgesic efficacy and safety of VVZ-149 Injections, which is under clinical development as a single-use injectable product for treating moderate to severe postoperative pain. Methods Sixty patients undergoing laparoscopic and robotic-laparoscopic gastrectomy were randomly assigned to receive a 10-hour intravenous infusion of VVZ-149 Injections or placebo, initiated approximately 1 hour before completion of surgical suturing. Major outcomes included pain intensity and opioid consumption via patient-controlled analgesia and rescue analgesia provided “as needed.” The treatment efficacy of VVZ-149 was further examined in a subpopulation requiring early rescue medication, previously associated with the presence of high levels of preoperative negative affect in a prior Phase 2 study (NCT02489526). Results Pain intensity was lower in the VVZ-149 (n = 30) than the placebo group (n = 29), reaching statistical significance at 4 hours post-emergence (P Conclusions VVZ-149 demonstrated effective analgesia with reduced postoperative pain and opioid requirements. Consistent with the results from the previous Phase 2 study, patients with early rescue requirement had greater benefit from VVZ-149, supporting the hypothesis that VVZ-149 may alleviate the affective component of pain and mitigate excessive use of opioids postoperatively.

Background In women undergoing cesarean delivery under spinal anesthesia with intrathecal morphine, transversus abdominis plane (TAP) block with bupivacaine hydrochloride (HCl) may not improve postsurgical analgesia. This lack of benefit could be related to the short duration of action of bupivacaine HCl. A retrospective study reported that TAP block with long-acting liposomal bupivacaine (LB) reduced opioid consumption and improved analgesia following cesarean delivery. Therefore, we performed a prospective multicenter, randomized, double-blind trial examining efficacy and safety of TAP block with LB plus bupivacaine HCl versus bupivacaine HCl alone. Methods Women (n = 186) with term pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomized (1:1) to TAP block with LB 266 mg plus bupivacaine HCl 50 mg or bupivacaine HCl 50 mg alone. Efficacy was evaluated in a protocol-compliant analysis (PCA) set that was defined a priori. The primary end point was total postsurgical opioid consumption (oral morphine equivalent dosing [MED]) through 72 hours. Pain intensity was measured using a visual analog scale. Adverse events (AEs) after treatment were recorded through day 14. Results Total opioid consumption through 72 hours was reduced with LB plus bupivacaine HCl versus bupivacaine HCl alone (least squares mean [LSM] [standard error (SE)] MED, 15.5 mg [6.67 mg] vs 32.0 mg [6.25 mg]). This corresponded to an LSM treatment difference of -16.5 mg (95% confidence interval [CI], -30.8 to -2.2 mg; P = .012). The area under the curve of imputed pain intensity scores through 72 hours supported noninferiority of LB plus bupivacaine HCl versus bupivacaine HCl alone (LSM [SE], 147.9 [21.13] vs 178.5 [19.78]; LSM treatment difference, -30.6; 95% CI, -75.9 to 14.7), with a prespecified noninferiority margin of 36 (P = .002). In an analysis of all treated patients, including those not meeting criteria for inclusion in the PCA, there was no difference in postsurgical opioid consumption between groups. In the LB plus bupivacaine HCl group, 63.6% of patients experienced an AE after treatment versus 56.2% in the bupivacaine HCl-alone group. Serious AEs after treatment were rare (≈3% in both groups). Conclusions TAP block using LB plus bupivacaine HCl as part of a multimodal analgesia protocol incorporating intrathecal morphine resulted in reduced opioid consumption after cesarean delivery in the PCA set. Results suggest that with correct TAP block placement and adherence to a multimodal postsurgical analgesic regimen, there is an opioid-reducing benefit of adding LB to bupivacaine TAP blocks after cesarean delivery (ClinicalTrials.gov identifier: NCT03176459).

Study objective VVZ-149 is a small molecule that inhibits the glycine transporter type 2 and the serotonin receptor 5-hydroxytryptamine 2A. In the present study, we investigated the efficacy and safety of VVZ-149 as a single-use injectable analgesic for treating moderate to severe postoperative pain after colorectal surgery. Design Randomized, parallel group, double-blind Phase 2 clinical trial ( NCT02489526 ). Setting 3 academic institutions in the United States. Patients 60 patients undergoing laparoscopic colorectal surgery. Interventions A continuous 8-h intravenous infusion of VVZ-149 Injections (n = 40) or placebo (n = 20) administered after emergence from anesthesia. Measurements The outcome measures included pain intensity (PI), opioid consumption via patient-controlled analgesia (PCA), and rescue dosing provided “as needed”. Early rescue dosing with opioids postoperatively was associated with preoperative negative affect (anxiety, depression, and pain catastrophizing), enabling it to be used as an indirect measure of the affective component of pain. Efficacy outcomes were compared between treatment groups based on preoperative negative affect and early rescue dosing of opioids. Main results Postoperative PI was non-significantly lower in patients receiving VVZ-149 compared to those receiving placebo. The VVZ-149 group had a 34.2% reduction in opioid consumption for 24 h post-dose, along with fewer PCA demands. Somnolence and headache was higher in the intervention group. For patients characterized by high levels of preoperative negative affect, the VVZ-149 group experienced a significant pain reduction and 40% less opioid use compared to the placebo group. Conclusions VVZ-149 resulted in a non-significant reduction of postoperative pain during the first 8 h after surgery. Post hoc analysis indicates that VVZ-149 may benefit patients with negative affect who otherwise have higher postoperative opioid use. Registration number www.clinicaltrials.gov , ID: NCT02489526.

To investigate efficacy and safety of liposomal bupivacaine (LB) transversus abdominis plane (TAP) block with or without intrathecal morphine (ITM) compared with ITM alone for postsurgical analgesia after cesarean delivery (CD).Multicenter, open-label, randomized trial (NCT03853694).Operating room.Women with term pregnancy of 37 to 42 weeks scheduled for elective CD under spinal anesthesia.Patients were randomized 1:1:1 to LB 266 mg TAP block alone (LB group), ITM 50 μg followed by LB 266 mg TAP block (LB + ITM group), or ITM 150 μg alone (ITM group). All groups received the same postsurgical multimodal analgesic regimen.The LB and LB + ITM groups were compared with the ITM group for all efficacy outcomes. Postsurgical opioid consumption in morphine milligram equivalents (MMEs) through 72 h was compared by assessing noninferiority before testing superiority. Postsurgical pruritus severity was assessed on an 11-point numerical rating scale.Between March 4, 2019, and January 10, 2020, 153 patients (LB, n = 52; LB + ITM, n = 48; ITM, n = 53) were enrolled. Baseline characteristics were comparable across groups. The LB group had statistically noninferior postsurgical opioid consumption through 72 h compared with the ITM group (least squares mean [LSM], 19.2 vs 16.4 MMEs; LSM treatment ratio, 1.17 [95% confidence interval (CI), 0.74-1.86]; noninferiority P 0.0034) as did the LB + ITM group (LSM, 14.6 vs 16.4 MMEs; LSM treatment ratio, 0.89 [95% CI, 0.55-1.44]; noninferiority P 0.0001). The LB and LB + ITM groups had significantly reduced pruritus severity scores through 12, 24, 48, and 72 h compared with the ITM group (P ≤ 0.0121). Adverse events occurred in 58%, 85%, and 81% of the LB, LB + ITM, and ITM groups, respectively.LB TAP block with or without ITM resulted in statistically noninferior postsurgical opioid consumption through 72 h, reduced pruritus, and favorable safety compared with ITM in women undergoing CD.

Background Context Although back pain is common among older adults, there is relatively little research on the course of back pain in this age group. Purpose Our primary goals were to report 2-year outcomes of older adults initiating primary care for back pain and to examine the relative importance of patient factors versus medical interventions in predicting 2-year disability and pain. Study Design/Setting This study used a predictive model using data from a prospective, observational cohort from a primary care setting. Patient Sample The study included patients aged ≥65 years at the time of new primary care visits for back pain. Outcome Measures Self-reported 2-year disability (Roland-Morris Disability Questionnaire [RDQ]) and back pain (0–10 numerical rating scale [NRS]). Methods We developed our models using a machine learning least absolute shrinkage and selection operator approach. We evaluated the predictive value of baseline characteristics and the incremental value of interventions that occurred between 0 and 90 days, and the change in patient disability and pain from 0 to 90 days. Limitations included confounding by indication and unmeasured confounding. Results Of 4,665 patients (89%) with follow-up, both RDQ (from mean 9.6 [95% confidence interval {CI} 9.4–9.7] to mean 8.3 [95% CI 8.0–8.5]) and back pain NRS (from mean 5.0 [95% CI 4.9–5.1] to mean 3.5 [95% CI 3.4–3.6]) scores improved slightly. Only 16% (15%-18%) reported no back pain-related disability or back pain at 2 years after initial visits. Regression model parameters explained 40% of the variation (R2) in 2-year RDQ scores, and the addition of 0- to 3-month change in RDQ score and pain improved prediction (R2=51%). The most consistent predictors of 2-year RDQ scores and back pain NRS scores were 0- to 90-day change in each respective outcome and patient confidence in improvement. Patients experienced 50% and 43% improvement in back pain and disability, respectively, 2 years after their initial visit. However, fewer than 20% of patients had complete resolution of their back pain and disability at that time. Conclusions Baseline patient factors were more important than early interventions in explaining disability and pain after 2 years.

OBJECTIVE: The utility of single-injection and continuous peripheral nerve blocks is limited by short duration of analgesia and catheter-related complications, respectively. This double-blind, multicenter trial evaluated the efficacy, safety, and pharmacokinetics of single-injection, ultrasound-guided brachial plexus block (BPB) with liposomal bupivacaine (LB) added to a standardized pain management protocol for shoulder surgery. METHODS: Adults undergoing total shoulder arthroplasty or rotator cuff repair were randomized to receive LB 133 mg, LB 266 mg (pharmacokinetic and safety analyses only), or placebo, added to a standardized analgesia protocol. The primary end point was area under the curve (AUC) of visual analog scale pain intensity scores through 48 hours postsurgery. Secondary end points were total opioid consumption, percentage of opioid-free patients, and time to first opioid rescue through 48 hours. Pharmacokinetic samples were collected through 120 hours and on days 7 and 10. Adverse events were documented. RESULTS: One hundred fifty-five patients received treatment (LB 133 mg, N = 69; LB 266 mg, N = 15; placebo, N = 71). BPB with LB 133 mg was associated with significantly improved AUC of pain scores (least squares mean [SE] = 136.4 [12.09] vs 254.1 [11.77], P

Objective. Opioids are frequently prescribed for chronic low back pain (CLBP), but there are broad individual differences in the benefits and risks of opioid therapy, including the development opioid-induced hyperalgesia. This study examined quantitative sensory testing (QST) data among a group of CLBP patients undergoing sustained oral opioid treatment. We investigated whether individual differences in psychological characteristics were related to opioid-induced changes in pain perception and pain modulation. Design. The six-month, open-label trial evaluated patients with low to high levels of negative affect (e.g., symptoms of distress, depression and anxiety); participants underwent QST at baseline (prior to initiating treatment) and during oral opioid treatment. Setting . A chronic pain management center. Patients. The 31 study participants had chronic discogenic back pain, with a pain intensity rating >3/10. Participants were divided into groups with high vs. low levels of Negative Affect (NA). Results. In the previously-published manuscript describing the clinical outcomes of the trial, high NA patients achieved only about half of the analgesic effect observed in the low NA group (Wasan AD, Michna E, Edwards RR, et al. Psychiatric comorbidity is associated prospectively with diminished opioid analgesia and increased opioid misuse in patients with chronic low back pain. Anesthesiology 2015;123:861–72). The QST findings reported here suggested that tolerance to experimental (cold pressor) pain and conditioned pain modulation tended to decrease in the high NA group over the course of opioid treatment, while temporal summation of mechanical pain declined in the low NA group. Conclusions. These results reveal that while the low NA group seemed to exhibit a generally adaptive, analgesic pattern of changes during opioid management, the high NA group showed a pattern more consistent with opioid-induced hyperalgesic processes. A greater susceptibility to hyperalgesia-promoting changes in pain modulation among patients with high levels of distress may contribute to a lower degree of benefit from opioid treatment in high NA patients.

ObjectiveTo estimate the prevalence of co-occurring pain sites among older adults with persistent back pain and associations of multisite pain with longitudinal outcomes.DesignSecondary analysis of a cohort study.SettingThree integrated health systems in the United States.SubjectsEight hundred ninety-nine older adults with persistent back pain.MethodsParticipants reported pain in the following sites: stomach, arms/legs/joints, headaches, neck, pelvis/groin, and widespread pain. Over 18 months, we measured back-related disability (Roland Morris, scored 0–24), pain intensity (11-point numerical rating scale), health-related quality of life (EuroQol-5D [EQ-5D], utility from 0–1), and falls in the past three weeks. We used mixed-effects models to test the association of number and type of pain sites with each outcome.ResultsNearly all (N = 839, 93%) respondents reported at least one additional pain site. There were 216 (24%) with one additional site and 623 (69%) with multiple additional sites. The most prevalent comorbid pain site was the arms/legs/joints (N = 801, 89.1%). Adjusted mixed-effects models showed that for every additional pain site, RMDQ worsened by 0.65 points (95% confidence interval [CI] = 0.43 to 0.86), back pain intensity increased by 0.14 points (95% CI = 0.07 to 0.22), EQ-5D worsened by 0.012 points (95% CI = –0.018 to –0.006), and the odds of falling increased by 27% (odds ratio = 1.27, 95% CI = 1.12 to 1.43). Some specific pain sites (extremity pain, widespread pain, and pelvis/groin pain) were associated with greater long-term disability.ConclusionsMultisite pain is common among older adults with persistent back pain. Number of pain sites was associated with all outcomes; individual pain sites were less consistently associated with outcomes.

Study Design. Secondary analysis of data from a double-blind randomized controlled trial. Objective. To identify mediators of the effect of lumbar epidural injections of corticosteroid plus lidocaine on patient satisfaction at 6 weeks postinjection in patients with lumbar spinal stenosis. We hypothesized that short-term (≤3 wk) change in leg pain would be a significant mediator of satisfaction. Summary of Background Data. No prior studies have identified mediators of effects of epidural injections on patient satisfaction with treatment of lumbar spinal stenosis. Methods. We used mediation analysis methods to examine selected intermediate variables (adverse events and change in leg pain, back pain, disability, depression, and fatigue at 3 wk) as potential mediators of the effect of lumbar epidural injections of corticosteroid plus lidocaine on patient satisfaction with treatment. We used the overall satisfaction item from the Swiss Spinal Stenosis Questionnaire as our primary outcome to measure patient satisfaction with the injection procedure at 6 weeks. Results. Among 400 patients randomized to receive epidural injections with corticosteroid plus lidocaine or with lidocaine alone, 369 had complete data for the satisfaction outcome and potential mediators and served as the analysis sample. Contrary to our expectations, 3-week change in leg pain intensity did not have significant mediation effects on patient satisfaction. Three-week change in disability as measured by the Roland-Morris Disability Questionnaire was a significant mediator of the effects of lumbar epidural corticosteroid injections on patient satisfaction at 6 weeks, explaining 48% to 60% of the treatment effect on satisfaction. Changes in pain intensity in the leg and back together explained very little of the treatment effect on satisfaction beyond the information contributed by disability change alone. We did not find other intermediate variables to be mediators of patient satisfaction. Conclusion. These findings support the current approach of examining disability as a primary patient-reported outcome in comparative effectiveness studies of lumbar spinal stenosis. Conclusion. Level of Evidence: 2

This analysis of the lumbar epidural steroid injections for spinal stenosis multicenter randomized controlled trial data identifies the degree of and risk factors for cortisol suppression after epidural steroid injections in older adults with spinal stenosis. Four hundred patients aged 50 years and older with back or leg pain and central lumbar spinal stenosis completed baseline demographic and psychosocial measures. Morning serum cortisol levels were measured at baseline and 3 weeks after initial injection. Patients were randomized to receive epidural injections of either local anesthetic with corticosteroid (n = 200) or local anesthetic only (n = 200). The specific corticosteroid was chosen at the treating physician's discretion (methylprednisolone, betamethasone, triamcinolone, or dexamethasone). Thirty-two patients (20.3%) treated with corticosteroid experienced cortisol reduction at 3 weeks of >50% compared with 10 patients (6.7%) treated with lidocaine only (adjusted treatment effect = 3.5, 95% confidence interval: 1.6-7.9, P = 0.002). The effect on 3-week cortisol changes did not differ by demographic or patient-level characteristics. Those treated with methylprednisolone or triamcinolone had an average 3-week cortisol reduction of 41.0% (P = 0.005) and 41.6% (P < 0.001) from baseline, respectively, whereas patients treated with betamethasone or dexamethasone were not significantly different than comparable patients in the lidocaine arm. The higher rates of cortisol suppression at 3 weeks in those receiving epidural corticosteroid injections, particularly with longer-acting insoluble corticosteroid formulations, are consistent with sustained systemic absorption of corticosteroid.

Electronic medical record (EMR) systems provide easy access to radiology reports and offer great potential to support quality improvement efforts and clinical research. Harnessing the full potential of the EMR requires scalable approaches such as natural language processing (NLP) to convert text into variables used for evaluation or analysis. Our goal was to determine the feasibility of using NLP to identify patients with Type 1 Modic endplate changes using clinical reports of magnetic resonance (MR) imaging examinations of the spine. Identifying patients with Type 1 Modic change who may be eligible for clinical trials is important as these findings may be important targets for intervention. Four annotators identified all reports that contained Type 1 Modic change, using N = 458 randomly selected lumbar spine MR reports. We then implemented a rule-based NLP algorithm in Java using regular expressions. The prevalence of Type 1 Modic change in the annotated dataset was 10%. Results were recall (sensitivity) 35/50 = 0.70 (95% confidence interval (C.I.) 0.52–0.82), specificity 404/408 = 0.99 (0.97–1.0), precision (positive predictive value) 35/39 = 0.90 (0.75–0.97), negative predictive value 404/419 = 0.96 (0.94–0.98), and F1-score 0.79 (0.43–1.0). Our evaluation shows the efficacy of rule-based NLP approach for identifying patients with Type 1 Modic change if the emphasis is on identifying only relevant cases with low concern regarding false negatives. As expected, our results show that specificity is higher than recall. This is due to the inherent difficulty of eliciting all possible keywords given the enormous variability of lumbar spine reporting, which decreases recall, while availability of good negation algorithms improves specificity.

Background Patients prescribed opioids for chronic pain may suffer from inadequate postoperative pain control. Ketamine is an adjuvant demonstrating analgesic and opioid-sparing effects. We hypothesize that an intravenous ketamine infusion in addition to opioid-based patient-controlled analgesia (PCA) improves postoperative pain relief in this patient population. Methods We evaluated 64 patients with chronic pain taking opioids undergoing nononcologic surgery. Patients were randomized to receive either postoperative hydromorphone PCA and continuous ketamine (0.2 mg/kg/hour), or hydromorphone PCA and saline. Patients provided numeric rating scale (NRS) pain scores for “worst,” “average,” and “least” pain following surgery. The primary outcome measure was change in patients' postoperative NRS scores compared with baseline NRS. Secondary and tertiary outcomes included postoperative day one 24-hour opioid use and the amount of opioid used 24 hours prior to hospital discharge. Results Fifty-nine patients were included in the analysis. Baseline patient characteristics were similar with the exception of age. Patients using ketamine had decreased “average” pain scores (percent change between postoperative and preoperative NRS) after surgery (13.5% decrease in the ketamine group vs 15.5% increase in NRS in the placebo group, P = 0.0057). There were no differences in “worst” or “least” pain scores or postoperative opioid use. Side effects between groups were similar. Conclusions Our study demonstrates that a postoperative ketamine infusion at 0.2 mg/kg/hour in addition to opioids results in a statistically significant reduction of “average” pain scores in patients undergoing surgery who take opioids for chronic pain. However, “least” and “worst” pain scores and the amount of opioid used postoperatively did not differ between groups. Thus, the use of a postoperative ketamine infusion at 0.2 mg/kg/hour provides limited benefit in improving pain management for this challenging population.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have analgesic, antipyretic, and anti-inflammatory effects.

Assessment of patients’ pain-related physical and emotional functioning is one of the most important measures in pain evaluation, and are two of the four key domains recommended by IMMPACT for interpreting the significance of treatment outcomes in clinical trials.

Objective To examine if a comorbid diagnosis of knee or hip osteoarthritis (OA) in older adults with new back pain visits is associated with long-term patient-reported outcomes and back-related health care use. Design Prospective cohort study. Setting Three integrated health systems forming the Back pain Outcomes using Longitudinal Data cohort. Participants Participants (N=5155) were older adults (≥65y) with a new visit for back pain and a complete electronic health record data. Interventions Not applicable; we obtained OA diagnoses using diagnostic codes in the electronic health record 12 months prior to the new back pain visit. Main Outcome Measures The Roland-Morris Disability Questionnaire (RDQ) and the EuroQol-5D (EQ-5D) were key patient-reported outcomes. Health care use, measured by relative-value units (RVUs), was summed for the 12 months after the initial visit. We used linear mixed-effects models to model patient-reported outcomes. We also used generalized linear models to test the association between comorbid knee or hip OA and total back-related RVUs. Results Of the 5155 participants, 368 (7.1%) had a comorbid knee OA diagnosis, and 94 (1.8%) had a hip OA diagnosis. Of the participants, 4711 (91.4%) had neither knee nor hip OA. In adjusted models, the 12-month RDQ score was 1.23 points higher (95% confidence interval [CI], 0.72–1.74) for patients with knee OA and 1.26 points higher (95% CI, 0.24–2.27) for those with hip OA than those without knee or hip OA, respectively. A lower EQ-5D score was found among participants with knee OA (.02 lower; 95% CI, −.04 to −.01) and hip OA diagnoses (.03 lower; 95% CI, −.05 to −.01) compared with those without knee or hip OA, respectively. Comorbid knee or hip OA was not significantly associated with total 12-month back-related resource use. Conclusions Comorbid knee or hip OA in older adults with a new back pain visit was associated with modestly worse long-term disability and health-related quality of life.

We report a previously undescribed complication associated with percutaneous maxillary nerve blockade. After the procedure, the patient reported an inability to close her ipsilateral eye (lagophthalmos). The patient had received 5 mL of 0.5% lidocaine for skin anesthesia. After needle placement was confirmed fluoroscopically, a combination of 80 mg methylprednisolone (2 mL) and 0.25% bupivacaine (3 mL) was administered. Symptoms resolved within 40 minutes. The likely cause was local anesthetic effect on the zygomatic branches of the facial nerve. When subcutaneous local anesthetic is given for maxillary block, smaller volumes should be considered. Doctors and patients should be aware of this complication, which may require treatment with artificial tears or patching of the eye to prevent corneal injury.

Background: Nucleoplasty is a minimally invasive procedure for treating pain caused by symptomatic disc herniation that is refractory to conservative therapy. Observational studies have reported differing outcomes for this procedure and thus its effectiveness is yet to be determined. Study design: A systematic review of the efficacy of the nucleoplasty procedure. Objectives: To assess the clinical efficacy of the nucleoplasty procedure for treating back pain from symptomatic, contained disc herniation and to evaluate the methodological quality of the included studies. Methods: The relevant literature for nucleoplasty was identified through a search of the following databases: Pubmed, Ovid Medline, and the Cochrane library, and by a review of the bibliographies of the included studies. A review of the literature of the effectiveness of the nucleoplasty procedure for managing discogenic pain was performed according to the criteria for observational studies using a “Quality Index” scale to determine the methodological quality of the literature. The level of evidence was classified as Level I, II, or III based on the quality of evidence developed by the United States Preventive Services Task Force (USPSTF) for therapeutic interventions. Recommendations were based on the criteria developed by Guyatt et al. Outcome measures: The main outcome measures evaluated were the percentage of pain relief based on visual analogue scale (VAS) or numeric rating scale (NRS), percentage of patients with more than 50% reduction in pain, percentage of patients meeting one or more success criteria after nucleoplasty, and improvement in patient function. Secondary measures noted were reports of complications and the Quality Index scores of each study that was evaluated. Results: The quality of evidence for improvement in pain or function after a nucleoplasty procedure is Level II-3. The recommendation is 1C/strong for the nucleoplasty procedure based on the quality of evidence available. The median Quality Index score was 16 (range 12 – 19), indicating adequate methodological quality of the available literature. None of the studies reported major complications related to nucleoplasty. Conclusions: Observational studies suggest that nucleoplasty is a potentially effective minimally invasive treatment for patients with symptomatic disc herniations who are refractory to conservative therapy. The recommendation is a level 1C, strongly supporting the therapeutic efficacy of this procedure. However, prospective randomized controlled trials with higher quality of evidence are necessary to confirm efficacy and risks, and to determine ideal patient selection for this procedure. Key words: Nucleoplasty outcomes, contained disc hernia­tion, percutaneous disc decompression, Quality Index, discogenic pain, systematic review

Nociceptive pain and its emotional component can result in the development of a "chronic pain memory". This report describes two patients who had long histories of chronic pain and opioid dependence. Both patients experienced sudden memory loss that was followed by significant pain reduction and an eradication of their need for opioid management. Neural centers involved in sensory pain, its affective component, opioid dependence, and memory overlap in the brain and share common pathways. The anterior cingulate cortex, the insular cortex, and the amygdala are examples of regions implicated in both pain and memory. One of the patients in the report experienced multiple seizure episodes, which may have contributed to memory loss and pain relief. The role of electroconvulsive therapy as it relates to amnesia and pain is reviewed. Questions are raised regarding whether therapies that address the memory component of pain may have a role in the treatment of long-term chronic pain patients.

To examine the incidence of abnormal urine toxicology screening among chronic pain patients prescribed opioids for their pain and to relate these results to patient descriptors and type, number, and dose of prescribed opioids.A retrospective analysis of data from 470 patients who had urine screening at a pain management program in an urban teaching hospital was performed. Urine samples were analyzed using gas chromatography-mass spectrometry. Patients were categorized as having urine screens that were "normal" (expected findings based on their prescribed drugs) or abnormal. Abnormal findings were those of (1) absence of a prescribed opioid, (2) presence of an additional nonprescribed controlled substance, (3) detection of an illicit substance, and (4) an adulterated urine sample.Forty-five percent of the patients were found to have abnormal urine screens. Twenty percent were categorized as having an illicit substance in their urine. Illicit substances and additional drugs were found more frequently in younger patients than in older patients (P0.001). No other variables were found to predict abnormal urine screen results.These results confirm past findings that random urine toxicology screens among patients prescribed opioids for pain reveal a high incidence of abnormal findings. Common patient descriptors, and number, type, and dose of prescribed opioids were found to be poor predictors of abnormal results.

Conditions described as "erythromelalgia" and "erythermalgia" are being formally specified by etiological diagnoses that enable the use of disease-modifying as well as symptomatic treatments. We describe an otherwise healthy 20-year-old man with acute-onset erythromelalgia. Severe bilateral distal limb pain and vasodilation persisted despite the use of many antihyperalgesics. Pathological examination of cutaneous nerve endings revealed severe small-fiber predominant axonopathy. Treatment of his apparent autoimmune polyneuropathy with high dose corticosteroids, 4 days of lidocaine infusion, and a prednisone taper cured him. Similarities to other cases allowed us to tentatively characterize a new treatable cause of erythromelalgia; acute adolescent autoimmune small-fiber axonopathy. In this report we evaluate various options for diagnosis and treatment.

Background: Opioids are frequently prescribed for chronic low back pain (CLBP), but there are little prospective data on which patient subgroups may benefit. Psychiatric comorbidity, such as high levels of depression and anxiety symptoms (termed comorbid negative affect [NA]), is a common presentation and may predict diminished opioid analgesia and/or increased opioid misuse. Methods: The authors conducted a 6½-month prospective cohort study of oral opioid therapy, with an active drug/placebo run-in period, in 81 CLBP patients with low, moderate, and high levels of NA. Treatment included an opioid titration phase with a prescribing physician blinded to NA group assignment and a 4-month continuation phase, during which subjects recorded daily pain levels using an electronic diary. The primary outcome was the percent improvement in average daily pain, summarized weekly. Results: There was an overall 25% dropout rate. Despite the high NA group being prescribed a higher average daily dose of morphine equivalents, linear mixed model analysis revealed that the 24 study completers in each of the high NA and low NA groups had an average 21 versus 39% improvement in pain, respectively (P < 0.01). The high NA group also had a significantly greater rate of opioid misuse (39 vs. 8%, P < 0.05) and significantly more and intense opioid side effects (P < 0.01). Conclusions: These results indicate that the benefit and risk considerations in CLBP patients with high NA versus low NA are distinctly different. Thus, NA is an important phenotypic variable to characterize at baseline, before deciding whether to prescribe opioids for CLBP.

STUDY DESIGN Prospective cohort study. OBJECTIVE To determine whether there are distinct trajectories of back pain and function among older adults and to identify characteristics that distinguish among patients with substantially different prognoses. SUMMARY OF BACKGROUND DATA Although the differential diagnosis and course of low back pain among older adults may differ from middle-aged adults, there is little evidence. Better understanding variability in recovery among older adults may help target patients for more intensive clinical interventions, plan resource use, and design clinical studies of more homogeneous patient groups. METHODS Patients aged 65 years or older with a new episode of care for back pain were recruited at 3 geographically diverse sites. Patients completed pain intensity and Roland-Morris Disability measures at baseline and 3, 6, and 12 months later. We used latent class analysis to identify distinct trajectories of pain and function and then logistic regression to identify predictors of membership in the improving trajectories. RESULTS There were 3929 participants who completed outcome measures at every follow-up interval. Latent class analysis identified subgroups with low, intermediate, or high pain or disability scores who remained relatively stable over time. However, small subgroups showed dramatic improvement from baseline to 1 year (17% with major improvement in Roland score, pain intensity, or both). Shorter pain duration, higher patient confidence in improvement, and fewer comorbid conditions at baseline were each associated independently with favorable prognosis. CONCLUSION Although most patients remained relatively stable over a year, latent class analysis identified small groups with major improvement in pain, function, or both. This technique may, therefore, be useful for studying back pain prognosis. Our results should help assemble more prognostically homogeneous groups for research, and the technique may help identify subgroups of patients with uniquely successful responses to investigational interventions. LEVEL OF EVIDENCE 3.

Importance In contrast to the recommendations for younger adults, many guidelines allow for older adults with back pain to undergo imaging without waiting 4 to 6 weeks. However, early imaging may precipitate interventions that do not improve outcomes. Objective To compare function and pain at the 12-month follow-up visit among older adults who received early imaging with those who did not receive early imaging after a new primary care visit for back pain without radiculopathy. Design, Setting, and Participants Prospective cohort of 5239 patients 65 years or older with a new primary care visit for back pain (2011-2013) in 3 US health care systems. We matched controls 1:1 using propensity score matching of demographic and clinical characteristics, including diagnosis, pain severity, pain duration, functional status, and prior resource use. Exposures Diagnostic imaging (plain films, computed tomography [CT], magnetic resonance imaging [MRI]) of the lumbar or thoracic spine within 6 weeks of the index visit. Main Outcome and Measures Primary outcome: back or leg pain–related disability measured by the modified Roland-Morris Disability Questionnaire (score range, 0-24; higher scores indicate greater disability) 12 months after enrollment. Results Among the 5239 patients, 1174 had early radiographs and 349 had early MRI/CT. At 12 months, neither the early radiograph group nor the early MRI/CT group differed significantly from controls on the disability questionnaire. The mean score for patients who underwent early radiography was 8.54 vs 8.74 among the control group (difference, −0.10 [95% CI, −0.71 to 0.50]; mixed model, P = .36). The mean score for the early MRI/CT group was 9.81 vs 10.50 for the control group (difference,−0.51 [−1.62 to 0.60]; mixed model, P = .18). Conclusions and Relevance Among older adults with a new primary care visit for back pain, early imaging was not associated with better 1-year outcomes. The value of early diagnostic imaging in older adults for back pain without radiculopathy is uncertain.

Neuropsychiatric disturbances are common in cancer patients. These occur in patients with and without pain, but at a much higher rate in those with pain. The most frequent pathologies are delirium, depression disorders, and anxiety disorders. Poorly treated pain can precipitate or exacerbate these disorders. It is difficult or impossible to obtain satisfactory pain relief in cancer patients with comorbid psychopathology, and these disorders significantly lower the quality of life in of themselves. Thus, it is important to recognize the presence of these disorders as part of the assessment of pain, and treat both conditions simultaneously. This paper outlines the salient features of the most common forms of psychopathology in cancer patients and their treatment.

Objective For interlaminar cervical epidural steroid injections (CESI) the lateral fluoroscopic view (LAT) is often considered to improve needle localization. However, the contralateral-oblique view (CLO) is a useful alternative with potential advantages to improve identification of cervical anatomy and needle depth assessment. The authors explored the attitudes and perceptions of pain medicine fellows currently training in two ACGME-accredited pain medicine fellowship programs regarding the use of these two types of fluoroscopic views. Methods The survey was conducted online following a request by e-mail. Of a total of 20 fellows who were contacted, there were 17 respondents who had experience with both techniques, and they were included for analysis. Results The response rate for participation was 95%. Whereas 70.6% respondents reported they were very certain about the assessment of anatomy with the CLO view, only 17.6% felt very certain with the LAT view. Compared with learning to perform interlaminar CESI using the LAT view only, the majority of fellows thought that using the CLO technique was easier to learn (P

Due to the complex interplay between physical, social, and psychological factors, the pain from fibromyalgia is extremely difficult to predict, prevent, or manage. Despite their efficacy, a number of challenges prevent the broader adoption of lifestyle interventions to treat fibromyalgia. A comprehensive management plan may involve using cognitive, behavioral, and physical therapeutic strategies in addition to the judicious use of medications. Lifestyle modification strategies for patients with fibromyalgia may include recommendations for increasing physical activity, dietary changes, weight reduction, improving the quality of sleep, and eliminating cigarette smoking.

Patients with fibromyalgia suffer from a myriad of symptoms across multiple functional domains. Attempts to offer these patients relief has led to a wide variation in the use of different treatment modalities, some of which have not been systematically studied and therefore have limited evidence basis for their efficacy. In this chapter, we review several treatment modalities for which there is limited evidence in the literature but that are commonly used by clinicians. Treatments reviewed here include: single modality approaches, complementary and alternative therapy, stretching and flexibility exercises, electrotherapy, pharmacotherapy with drugs such as opioids and benzodiazepines, and the use of interventional therapy such as trigger point injections.

Objective To determine the overall long-term effectiveness of treatment with epidural corticosteroid injections for lumbar central spinal stenosis and the effect of repeat injections, including crossover injections, on outcomes through 12 months. Design Multicenter, double-blind, randomized controlled trial comparing epidural injections of corticosteroid plus lidocaine versus lidocaine alone. Setting Sixteen clinical sites. Participants Participants with imaging-confirmed lumbar central spinal stenosis (N=400). Interventions Participants were randomized to receive either epidural injections with corticosteroid plus lidocaine or lidocaine alone with the option of blinded crossover after 6 weeks to receive the alternate treatment. Participants could receive 1 to 2 injections from 0 to 6 weeks and up to 2 injections from 6 to 12 weeks. After 12 weeks, participants received usual care. Main Outcome Measures Primary outcomes were the Roland-Morris Disability Questionnaire (RDQ) (range, 0–24, where higher scores indicate greater disability) and leg pain intensity (range, 0 [no pain] to 10 [pain as bad as you can imagine]). Secondary outcomes included opioid use, spine surgery, and crossover rates. Results At 12 months, both treatment groups maintained initial observed improvements, with no significant differences between groups on the RDQ (adjusted mean difference, −0.4; 95% confidence interval [CI], −1.6 to 0.9; P=.55), leg pain (adjusted mean difference, 0.1; 95% CI, −0.5 to 0.7; P=.75), opioid use (corticosteroid plus lidocaine: 41.4% vs lidocaine alone: 36.3%; P=.41), or spine surgery (corticosteroid plus lidocaine: 16.8% vs lidocaine alone: 11.8%; P=.22). Fewer participants randomized to corticosteroid plus lidocaine (30%, n=60) versus lidocaine alone (45%, n=90) crossed over after 6 weeks (P=.003). Among participants who crossed over at 6 weeks, the 6- to 12-week RDQ change did not differ between the 2 randomized treatment groups (adjusted mean difference, −1.0; 95% CI, −2.6 to 0.7; P=.24). In both groups, participants crossing over at 6 weeks had worse 12-month trajectories compared with participants who did not choose to crossover. Conclusions For lumbar spinal stenosis symptoms, epidural injections of corticosteroid plus lidocaine offered no benefits from 6 weeks to 12 months beyond that of injections of lidocaine alone in terms of self-reported pain and function or reduction in use of opioids and spine surgery. In patients with improved pain and function 6 weeks after initial injection, these outcomes were maintained at 12 months. However, the trajectories of pain and function outcomes after 3 weeks did not differ by injectate type. Repeated injections of either type offered no additional long-term benefit if injections in the first 6 weeks did not improve pain.