Average Pain Intensity Score Research Articles

Randomized, double-blind, placebo-controlled trial of ISC 17536, an oral inhibitor of transient receptor potential ankyrin 1, in patients with painful diabetic peripheral neuropathy: impact of preserved small nerve fiber function.

Patients with chronic pain syndromes, such as those with painful peripheral neuropathy due to diabetes mellitus, have limited treatment options and suffer ongoing attrition of their quality of life. Safer and more effective treatment options are needed. One therapeutic approach encompasses phenotypic characterization of the neuropathic pain subtype, combined with the selection of agents that act on relevant mechanisms. ISC 17536 is a novel, orally available inhibitor of the widely expressed pain receptor, transient receptor potential ankyrin 1, which mediates nociceptive signaling in peripheral small nerve fibers. In this randomized, placebo-controlled, proof-of-concept trial, we assessed the safety and efficacy of 28-day administration of ISC 17536 in 138 patients with chronic, painful diabetic peripheral neuropathy and used quantitative sensory testing to characterize the baseline phenotype of patients. The primary end point was the change from baseline to end of treatment in the mean 24-hour average pain intensity score based on an 11-point pain intensity numeric rating scale. The study did not meet the primary end point in the overall patient population. However, statistically significant and clinically meaningful improvement in pain were seen with ISC 17536 in an exploratory hypothesis-generating subpopulation of patients with preserved small nerve fiber function defined by quantitative sensory testing. These results may provide a mechanistic basis for targeted therapy in specific pain phenotypes in line with current approaches of "precision medicine" or personalized pain therapeutics. The hypothesis is planned to be tested in a larger phase 2 study.

Frequency and Severity of Phantom Limb Pain in Veterans with Major Upper Limb Amputation: Results of a National Survey.

To describe the frequency and severity of phantom limb pain (PLP) in veterans with major upper limb amputation and determine the association between PLP and person, amputation, and prosthesis characteristics. Cross-sectional design. National survey of veterans living in the community. U.S. military veterans (N = 776) with major upper limb amputations. Frequency and intensity of PLP, person characteristics such as age and gender, amputation characteristics such as level and etiology, and prosthesis characteristics such as type and intensity of prosthesis use. Respondents were 97% male with a mean age of 63 years and a mean time since amputation of 31 years. The most common amputation level was transradial (36%) and 62% reported accident as the amputation etiology. 73% of amputees reported PLP with a mean intensity score of 4.2 (standard deviation 3.4). PLP frequency in the daily to always category was reported in 42% of amputees. Weekly and more frequent residual limb pain was associated with having any PLP. Amputation at the shoulder (odds ratio [OR] 3.78 [1.93, 7.39]), amputation at the transhumeral level (OR 1.76 [1.10,2.81]), and amputation due to cancer (OR 5.33 [1.15, 24.81]) were also associated with any PLP. Moderate (β = 1.34, P = < .001) and severe (β = 3.31, P < .001) residual limb pain intensity was associated with higher PLP intensity among those with pain. Amputation at the shoulder level was associated with a 1.5 points higher average pain intensity score (P < .001) compared to the transradial level. Multivariable models failed to show an association between PLP prevalence and amputation of the dominant limb (P = .08) and PLP was not associated with intensity of daily prosthesis use in bivariate analyses. This study of a large cohort of veterans with major upper limb amputation highlights the long-term persistence of moderate frequency and intensity PLP.

Abstract C005: Racial differences in painful body surface area (bSA) and pain intensity among hospice cancer patients

Abstract Introduction: Although pain is subjective and highly variable between individuals, little is known about the amount of body surface area (BSA) that represents chronically painful locations reported by patients with cancer. The purpose of this study was to explore associations between BSA and demographic, cancer, and other pain variables. Methodology: We used baseline data from a five-step, stepped-wedge randomized clinical trial of cancer patients receiving hospice care. Participants were 259 hospice patients (51% female; mean age 68.4±14.2; 34% Black, 50% White, 14% Other race; 18% Hispanic) who completed PAINReportIt, a measure of pain as a multi-dimensional phenomenon. This computerized software design allowed patients to (a) draw on front and back body outlines where they had pain, (b) select numbers from 0-10 to report their current, least and worst pain intensity in the past 24 hours, and (c) indicate their age, gender, race, ethnicity and type of cancer. We used a novel algorithm with the ImageJ software to calculate the BSA from the digital pain drawings and the R statistical program to conduct descriptive, correlational, and ANOVA analyses. Results: The other race group included 2 Asians, 35 Hispanics and 5 non-Hispanic Other. The three largest painful BSAs for a body region were located in the abdomen (12.0%±18.8%), lower back (6.8%±12.6%), and upper back (4.2%±9.3%). Patients’ average pain intensity scores were: Now (4.7±2.6), Least (3.2±2.4) and Worst (7.0±2.4). Differences by race were noted for the total BSA (p=.03), pain now (p=.02), and pain worst (p=.03). Blacks reported the lowest total BSA, Whites the lowest pain now and worst pain, and the Other racial group the highest total BSA, pain now and pain worst. With Bonferroni adjustment, Other and Black differed on BSA (p=.02) and Other and White differed on pain now (p=.05). Total BSA was significantly correlated with pain now (r=.17, p=.01), pain least (r=.15, p=.02), pain worst (r=.24, p&amp;lt;.001), and the number of sites (r=.31, p&amp;lt;.001). Total BSA was not significantly associated with type of cancer, but regions with highest total BSA were consistent with primary cancer site. Conclusion: Our sample included a large number of patients from minority groups. Based on known disparities in pain control between Blacks and Whites, our findings are surprising. Findings may reflect culturally competent care that still requires greater attention to reduce the severity of worst pain. Reasons for differences in pain dimensions by racial groups and not for the type of cancer are unclear from our initial study of BSA among patients receiving hospice care. In the future, studies are needed to understand these differences and explore if other pain dimensions like pain quality and pain pattern differ by race and ethnicity, since individuals identifying as Hispanic had the highest BSA and pain intensity. Citation Format: Tanaia Marshall, Roach Keesha, Prashant Singh, Yingwei Yao, Diana Wilkie. Racial differences in painful body surface area (bSA) and pain intensity among hospice cancer patients [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C005.

Discrete and Dynamic Postoperative Pain Catastrophizing Trajectories Across 6 Months: A Prospective Observational Study

ObjectivesTo investigate pain catastrophizing presentations up to 6 months postoperatively and subsequent changes in pain intensity and physical function. DesignProspective observational multisite study. SettingTwo tertiary care facilities between 2016 and 2019. Participants: Adult patients (N=348) undergoing a mastectomy, thoracic surgery, total knee or hip arthroplasty, spinal fusion, or major abdominal surgery. InterventionsNot applicable. Main Outcome MeasuresPain Catastrophizing Scale scores, Defense and Veterans Pain Rating Scale, average pain intensity, and Patient Reported Outcomes Measurement Information System (PROMIS) physical function. ResultsFour pain catastrophizing trajectories were identified in 348 surgical patients during the 6 months of postoperative recovery: stable, remitting, worsening, and unremitting. Linear mixed-effects models found that the unremitting trajectory was associated with higher pain intensity over time. The average pain intensity of participants in the remitting trajectory was estimated to decrease at a faster rate over the 6 months after surgery than pain of other trajectories, despite participants reporting high preoperative Pain Catastrophizing Scale and pain scores. Worsening and unremitting trajectories were associated with reduced physical function. Preoperative average pain intensity scores were not associated with postoperative physical function scores, nor were participants’ preoperative physical function scores associated with average pain intensity scores postoperatively. Prolonged hospitalization, smoking, and preoperative opioid prescriptions were associated with the unremitting trajectory. ConclusionsFindings suggest that preoperative pain catastrophizing scores alone may not be adequate for estimating long-term patient-reported outcomes during postoperative rehabilitation. Pain catastrophizing has a dynamic presentation and is associated with changes in pain intensity and physical function up to 6 months postoperatively. Routine assessments can inform the delivery of early interventions to surgical patients at risk of experiencing a pain catastrophizing trajectory associated with suboptimal outcomes during rehabilitation.

PRO83 PATIENT-REPORTED SYMPTOM BURDEN OF CHARCOT-MARIE-TOOTH DISEASE TYPE 1A IN EUROPE AND THE US MEASURED USING A DIGITAL APP

To examine patient-reported symptom burden for Charcot-Marie-Tooth disease type 1A (CMT1A) in Europe and the US. Adults with CMT1A were recruited to a two-year international observational study exploring the real-world impact of the disease. Data were collected via CMT&Me, a digital app developed for this study, through which participants were asked questions about quality of life (QoL) via patient-reported outcome measures. This interim analysis examined symptom burden of CMT1A in participants from Germany, Italy, Spain, the UK, and the US. At symptom onset (mean age 17 years), 39% and 10% of participants reported moderate and severe symptoms, respectively. Mean participant age at diagnosis was 26 years, at which participants reported symptoms to be moderate (59%) and severe (25%), with symptoms worsening between the two timepoints in 47% of participants (n=450). The mean number of years since diagnosis was reported to be 19, although there was high variance. The most important CMT symptoms (n=450) were difficulty walking (most important), weakness in feet, weakness in legs, weakness in hands and fingers, and problems with balance (fifth most important). Twenty percent of participants (n=269) experienced cramps daily, while 47% experienced them every 1-4 days. Most participants (55%) rated the cramps they experienced as either severe or moderate. Average PROMIS pain intensity (n=274) and Brief Fatigue Inventory (n=258) scores indicated moderate symptom impact on QoL. The symptom burden of CMT1A is wide-reaching and affects people with the disease according to differing severities in terms of physical limitations, cramps, pain, and fatigue.

Predicting Acute Postoperative Pain Trajectories and Long-Term Outcomes of Adolescents after Spinal Fusion Surgery.

Objectives Acute pain trajectories are associated with long-term outcomes such as persistent pain and functional disability in adults. However, there are limited data on acute postoperative pain trajectories in the pediatric population. The aims of this study were to investigate acute postoperative pain trajectories, their predictors, and their impact on long- term outcomes in adolescents with idiopathic scoliosis. Methods We evaluated the preoperative pain intensity, use of analgesics, psychosocial measures and physical functioning of adolescents scheduled to undergo spinal fusion, and their average 6-hour self-reported pain intensity scores for their entire hospital stay. Six months after surgery, baseline variables were reassessed. We used growth mixture modeling to conduct acute postoperative pain trajectory analysis and to identify predictors of pain trajectories. Generalized linear models were conducted to determine whether acute pain trajectories predict long-term outcomes. Results One hundred and six patients were included in the best-fitted acute pain trajectory model that included four classes that differed in initial pain intensity and rates of change over time. Preoperative pain catastrophizer status and use of analgesics significantly predicted pain trajectory membership. Furthermore, at the 6-month follow-up, patients experiencing moderate-to-severe pain in the acute postoperative period were more likely to report higher levels of pain severity, use pain medication, and miss a greater number of school/work days due to back pain in the last three months. Discussion. Preoperative assessment and analyzing the progression of pain in the acute postoperative period can help identify those at risk of negative long-term outcomes after surgery.

Deficits in pain medication in older adults with chronic pain receiving home care: A cross-sectional study in Germany.

ObjectiveTo analyze the pattern and appropriateness of pain medications in older adults receiving home care.MethodsWe performed a prospective cross-sectional study in patients ≥65 years old having chronic pain and receiving home care in Berlin, Germany. Data on prescribed pain medications were collected using self-reported information, nursing documents, and medication plans during interviews at home. Pain intensity was determined with the numeric rating scale (NRS) and the Pain Assessment In Advanced dementia (PAINAD) scale. The Pain Medication Appropriateness Scale score (SPMAS) was applied to evaluate inappropriateness (i.e. a score ≤67) of pain medication.ResultsOverall 322 patients with a mean age of 82.1 ± 7.4 years (71.4% females) were evaluated. The average pain intensity scores during the last 24 hours were 5.3 ± 2.1 and 2.3 ± 2.3 on NRS and PAINAD scale (range 0–10, respectively). Sixty (18.6%) patients did not receive any pain medication. Among the treated patients, dipyrone was the most frequently prescribed analgesic (71.4%), while 50.8% and 19.1% received systemic treatment with opioids and non-steroidal anti-inflammatory drugs, respectively. The observed median SPMAS was 47.6 (range 0–100) with 58 (18.0%) of patients achieving appropriate values. Half of the patients were treated with scheduled, while 29.9% were only treated with on-demand medications. Cognitive status had no effect on appropriateness of pain treatment.ConclusionsWe observed substantial deficits in dosing patterns and appropriateness of pain medication in older adults with pain receiving home care. This applied to both patients with and without severe cognitive impairment.

Percutaneous Peripheral Nerve Stimulation (PNS) for the Treatment of Chronic Low Back Pain Provides Sustained Relief

The objective of this study was to evaluate the use of percutaneous peripheral nerve stimulation (PNS) for the treatment of chronic low back pain (LBP). Percutaneous PNS offers the potential to provide an effective neuromodulation therapy using a system and fine-wire leads designed specifically for percutaneous use with history of an excellent safety profile. Subjects with chronic axial LBP received percutaneous PNS leads targeting the medial branch of the dorsal ramus in the region of LBP. Lead placement was guided using ultrasound and confirmed by selective activation of the lumbar multifidus and patient-reported sensations. The percutaneous fine-wire leads remained in place for the 30-day therapy. A majority of subjects reported statistically and clinically significant reductions in both average pain intensity (BPI-5) and worst pain intensity (BPI-3) scores with PNS treatment, which continued long term at the four-month follow-up visit. Subject-reported reductions in pain intensity were substantiated by concomitant and sustained reductions in analgesic medication usage. Subjects also reported clinically significant reductions in patient-centric outcomes of disability (Oswestry Disability Index), pain interference (BPI-9), and patient global impression of change (PGIC). This work demonstrates the potential value of percutaneous PNS for the treatment of chronic LBP. Improvements in pain, medication, and patient-centric outcomes, which were sustained long term after the removal of PNS leads, demonstrate the significance of this innovative approach to treat chronic LBP.

Vulvodynia, “A Really Great Torturer”: A Mixed Methods Pilot Study Examining Pain Experiences and Drug/Non-drug Pain Relief Strategies

BackgroundWomen with vulvodynia, a chronic pain condition, experience vulvar pain and dyspareunia. Few studies examine the range and combination of treatment strategies that women are actually using to reduce vulvodynia. AimTo describe pain experiences and pain relief strategies of women with vulvodynia. MethodsConvenience sample, 60 women with vulvodynia (median age 32.5 [interquartile range {IQR} 8.5] years; 50 white, 10 racial/ethnic minorities) completed PAINReportIt and reported use of drugs and alcohol and responded to open-ended questions. Univariate descriptive statistics and bivariate inferential tests were used to describe average pain intensity scores, alcohol use, smoking, number of pain relief strategies, and their associations. Women’s open-ended responses about their pain experiences and drug and non-drug pain relief strategies (NDPRS) were analyzed for patterns. OutcomesOur mixed methods analysis connected data from pain measures, prescribed treatments and self-reported behaviors with women’s free responses. This enabled nuanced insights into women’s vulvodynia pain experiences. ResultsWomen’s descriptions of their pain and suffering aligned with their reported severe pain and attempts to control their pain, with a median pain intensity of 6.7 (IQR 2.0) despite use of adjuvant drugs (median 2.0 [IQR 2.0]), and opioids (median 1.0 [IQR 2.0]). 36 women (60%) used alcohol to lessen their pain. 26 women (43%) listed combining analgesics and alcohol to relieve their pain. 30 women (50%) smoked cigarettes. 54 women (90%) used ≥1 NDPRS. The mean number of NDPRS used was 2.1 ± 1.3 (range 0–6). The 5 most common NDPRS from women’s comments were herbal medicine (40%), acupuncture (27%), massage (22%), hypnosis (15%), and mental healthcare (13%). Clinical ImplicationsSevere pain in women with vulvodynia may be a clinical indicator of those at higher risk of combining prescription pain medications with alcohol, which are all central nervous system depressants and may potentiate overdose. Strengths and LimitationsThis pilot study demonstrated that the mixed methods approach to help understand the complexity of vulvodynia was feasible. We identified data showing a reliance on a high-risk mix of prescriptions and alcohol to reduce vulvodynia pain and a high prevalence of cigarette smoking. However, as a pilot study, these results are considered preliminary; the sample may not be representative. Perhaps only women at the extreme end of the pain continuum participated, or women took the survey twice because identifiers were not collected. ConclusionDespite attempts to reduce pain using multiple therapies, including alcohol, women’s vulvodynia pain is severe and not controlled.Schlaeger JM, Pauls HA, Powell-Roach KL, et al. Vulvodynia, “A Really Great Torturer”: A Mixed Methods Pilot Study Examining Pain Experiences and Drug/Non-drug Pain Relief Strategies. J Sex Med 2019;16:1255–1263.

Rescue Analgesic Medication Use by Patients Treated with Triamcinolone Acetonide Extended-Release for Knee Osteoarthritis Pain: Pooled Analysis of Three Phase 2/3 Randomized Clinical Trials.

IntroductionIn clinical trials for knee osteoarthritis (OAK), rescue medication is commonly provided to manage uncontrolled index-knee pain. The impact of treatment on rescue medication utilization provides important information on the robustness of analgesic effect. In randomized controlled OAK trials (NCT01487161, NCT02116972, NCT02357459), intra-articular (IA) triamcinolone acetonide extended-release (TA-ER) demonstrated substantial, prolonged analgesia versus saline-placebo and TA crystalline solution (TAcs) as assessed by patient-reported pain scales. This pooled analysis assessed the impact of TA-ER on rescue medication use.MethodsPatients (N = 798) with OAK (American College of Rheumatology criteria; Kellgren–Lawrence grade 2/3) and baseline average daily pain intensity score ≥ 5 to ≤ 9 (0–10 numeric rating scale) received a single IA injection of TA-ER (N = 324), saline-placebo (N = 262), or TAcs (N = 212). Acetaminophen/paracetamol tablets were provided to treat uncontrolled pain (knee or otherwise). Rescue medication consumption was monitored through a daily diary; pill counts were confirmed at the clinical site. Differences in rescue medication use were measured by least-squares mean (LSM) differences, number of rescue medication tablets used per day, and in area under the effect (AUE) curves of rescue medication tablets used per week.ResultsThe overall number of rescue medication tablets used per day through week 24 was significantly less (p ≤ 0.05) for TA-ER versus saline-placebo (LSM difference, − 0.43) and TAcs (− 0.24). Rescue medication use was significantly (p ≤ 0.05) lower following TA-ER versus saline-placebo across weeks 1–12 (AUEweeks1–12; LSM difference, − 24.5) and weeks 1–24 (AUEweeks1–24; − 51.6) and versus TAcs across weeks 1–12 (AUEweeks1–12; − 21.1).ConclusionsIn patients with painful OAK, reduced rescue medication use may be a potential benefit of TA-ER and further supports its analgesic efficacy. Additional research is needed to assess whether TA-ER impacts the use of other common oral analgesics (nonsteroidal anti-inflammatory drugs, opioids) for patients with OAK.FundingFlexion Therapeutics, Inc., Burlington, MA, USA.Plain Language SummaryPlain language summary available for this article.

Analgesic efficacy, safety, and tolerability of a long-acting abuse-deterrent formulation of oxycodone for moderate-to-severe chronic low back pain in subjects successfully switched from immediate-release oxycodone.

ObjectivesThis post hoc analysis of data from a randomized, double-blind, placebo-controlled, enriched-enrollment randomized-withdrawal Phase III study evaluated the safety, tolerability, and analgesic efficacy of Oxycodone DETERx extended-release (ER), abuse-deterrent capsules (Xtampza® ER) in subjects with chronic low back pain who were successfully transitioned from immediate-release (IR) oxycodone.MethodsContinuous outcomes were analyzed using a mixed-model repeated-measures approach; binomial outcomes were analyzed using chi-squared; and time-to-event outcomes using Kaplan–Meier analyses.ResultsA total of 110 subjects previously prescribed IR oxycodone entered the Open-label Titration Phase. Forty-four subjects were randomized to Oxycodone DETERx (n=22) or placebo (n=22) in the 12-week Double-blind Maintenance Phase. Efficacy results in this subgroup showed a statistically significant difference between Oxycodone DETERx and placebo in average pain intensity scores from Randomization Baseline to Week 12 (least squares mean [± standard error], −1.88 [0.70]; P=0.0078). Additional efficacy results indicated that Oxycodone DETERx vs placebo was associated with a statistically significant benefit in durability of effect from Week 2 through Week 12 (P<0.01), numbers of subjects with a ≥30% (n [%] 10 [45.5%] vs 0 [0%]; P=0.0004) and ≥50% (10 [45.5%] vs 0 [0%]; P=0.0004) improvement in pain intensity, longer time-to-exit (P=0.0014), a greater number of subjects who completed the study (14 [63.6%] vs 4 [18.2%]), and less rescue medication use (acetaminophen; mean [SD], 163.5 [337.8] mg) vs 216.2 [377.3] mg). Adverse event profiles were consistent with opioid class effects and results from the original study; Oxycodone DETERx was well tolerated in subjects previously treated with short-acting oxycodone.ConclusionsOxycodone DETERx resulted in clinically meaningful and statistically significant efficacy in subjects with chronic low back pain who were previously prescribed IR oxycodone and were successfully switched to ER Oxycodone DETERx.

MP39-08 PAINFUL URGENCY AND/OR PAINFUL FILLING PREDICTIVE OF SOMATIC SYMPTOMS AND CHRONIC PAIN IN WOMEN WITH OVERACTIVE BLADDER

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis1 Apr 2018MP39-08 PAINFUL URGENCY AND/OR PAINFUL FILLING PREDICTIVE OF SOMATIC SYMPTOMS AND CHRONIC PAIN IN WOMEN WITH OVERACTIVE BLADDER Casey G Kowalik, Sophia Delpe, Melissa R. Kaufman, Roger R. Dmochowski, and W. Stuart Reynolds Casey G KowalikCasey G Kowalik More articles by this author , Sophia DelpeSophia Delpe More articles by this author , Melissa R. KaufmanMelissa R. Kaufman More articles by this author , Roger R. DmochowskiRoger R. Dmochowski More articles by this author , and W. Stuart ReynoldsW. Stuart Reynolds More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1255AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Current theories hypothesize that overactive bladder (OAB) and Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) comprise a spectrum of bladder hypersensitivity with overlapping symptoms. Symptoms of painful urgency and filling are common in women with OAB and may be correlated with more severe urologic symptoms and decreased quality of life. This analysis investigated the relationships of painful urgency and filling with somatic symptoms and chronic pain conditions in women with OAB without an IC/BPS diagnosis. METHODS Women with OAB symptoms and without IC/BPS diagnosis were recruited to complete validated questionnaires assessing urinary symptoms (OAB symptom scale [OAB-ss] and Health Related Quality of Life [OABq-HRQL]), somatic symptoms, and pain syndromes. Participants were categorized into 3 groups, (1) Neither (2) Either or (3) Both, based on their report of painful urgency and/or painful filling. Multivariable regression analyses were performed to determine factors predictive of have either or both painful urgency and/or painful filling. RESULTS Of 218 women with OAB symptoms, 46% (n=101) had neither painful urgency nor painful filling, 43% (n=94) had either, and 11% (n=23) had both. There was an increase in average OAB-SS, pain intensity, and somatic symptom score, and a decrease in OAB-HRQL from neither > either > both. Controlling for age, women with either or both urologic pain symptoms had an increase in somatic symptom score by 1.5 and 3 points and an increase in pain intensity by 3 and 6.5 points, respectively, compared to women in the neither group. Additionally, women with either or both symptoms were 2.9 and 3.5 times more likely to have irritable bowel syndrome and 3.3 and 4.5 times, respectively, more likely to have chronic pelvic pain. CONCLUSIONS In this group of women with OAB, without IC/BPS, the majority reported either painful urgency, painful filling, or both. Experiencing painful urgency and/or filling was associated with increased somatic symptom burden and pain intensity. Additionally, women with either or both symptoms were more likely to have chronic pain conditions, hypothesized to have a common central pathophysiology. These findings support the hypothesis that OAB and IC/BPS diagnoses may represent a continuum of bladder hypersensitivity with women experiencing pain being more likely to also have underlying central sensitization mechanisms. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e512-e513 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Casey G Kowalik More articles by this author Sophia Delpe More articles by this author Melissa R. Kaufman More articles by this author Roger R. Dmochowski More articles by this author W. Stuart Reynolds More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Fulranumab in patients with interstitial cystitis/bladder pain syndrome: observations from a randomized, double-blind, placebo-controlled study

BackgroundThis study was designed to evaluate the efficacy and safety of fulranumab, a fully human monoclonal antibody directed against nerve growth factor (NGF), for pain relief in patients with interstitial cystitis/bladder pain syndrome (IC/BPS).MethodsIn this multicenter, double-blind study, adults with IC/BPS (i.e., interstitial cystitis symptom index [ICSI] total score ≥8) accompanied by chronic, moderate-to-severe pain were randomized to fulranumab 9 mg or matching placebo, administered subcutaneously at weeks 1, 5, and 9. The primary efficacy endpoint was change from baseline to study endpoint (week 12 or at withdrawal) in average daily pain intensity score. Key secondary endpoints included change from baseline to study endpoint in worst pain intensity score, ICSI total score, Pelvic Pain and Urgency/Frequency total score, Patient Perception of Bladder Condition score, and global response assessment.ResultsThis study was terminated prematurely based on concern that this class may be associated with rapidly progressing osteoarthritis or osteonecrosis. Thirty-one patients (of the targeted 70 patients) were randomized, 17 to placebo and 14 to fulranumab, with 15 and 10 patients, respectively, receiving all 3 doses of double-blind treatment. In ANOVA analyses, there was no statistically significant difference between treatment groups for the primary endpoint (LS mean difference [95% CI] vs. placebo, −0.2 [−1.52, 1.10]) or any of the secondary endpoints. Fulranumab was well tolerated, with no patient discontinuing due to an adverse event or experiencing a joint-related serious adverse event over a 26-week follow-up period. No events related to the neurologic or motor systems were reported.ConclusionsEfficacy was not demonstrated in the present study with the single dose tested and a limited sample size, leading to lack of statistical power. These findings do not exclude the possibility that fulranumab would provide clinical benefit in a larger study and/or specific populations (phenotypes) in this difficult to treat pain condition.Trial registrationNCT01060254, registered January 29, 2010.

Persistent Breast Pain Among Women With Histories of Breast-conserving Surgery for Breast Cancer Compared With Women Without Histories of Breast Surgery or Cancer.

This study compared persistent breast pain among women who received breast-conserving surgery for breast cancer and women without a history of breast cancer. Breast cancer survivors (n=200) were recruited at their first postsurgical surveillance mammogram (6 to 15 mo postsurgery). Women without a breast cancer history (n=150) were recruited at the time of a routine screening mammogram. All women completed measures of breast pain, pain interference with daily activities and intimacy, worry about breast pain, anxiety symptoms, and depression symptoms. Demographic and medical information were also collected. Persistent breast pain (duration ≥6 mo) was reported by 46.5% of breast cancer survivors and 12.7% of women without a breast cancer history (P<0.05). Breast cancer survivors also had significantly higher rates of clinically significant persistent breast pain (pain intensity score ≥3/10), as well as higher average breast pain intensity and unpleasantness scores. Breast cancer survivors with persistent breast pain had significantly higher levels of depressive symptoms, as well as pain worry and interference, compared with survivors without persistent breast pain or women without a breast cancer history. Anxiety symptoms were significantly higher in breast cancer survivors with persistent breast pain compared with women without a breast cancer history. Results indicate that persistent breast pain negatively impacts women with a history of breast-conserving cancer surgery compared with women without that history. Strategies to ameliorate persistent breast pain and to improve adjustment among women with persistent breast pain should be explored for incorporation into standard care for breast cancer survivors.

Preoperative Pain, Symptoms, and Psychological Factors related to Higher Acute Pain Trajectories during Hospitalization for Total Knee Arthroplasty

ObjectivesUnrelieved postoperative pain after total knee arthroplasty (TKA) is a significant problem. This longitudinal study investigated how preoperative pain intensity, as well as a comprehensive list of preoperative and perioperative factors, influenced the severity of acute average and worst pain after TKA.MethodsPrior to surgery, 203 patients completed a demographic questionnaire, Lee Fatigue Scale, Fatigue Severity Scale, Hospital Anxiety and Depression Scale, and Brief Illness Perception Questionnaire. Brief Pain Inventory was completed prior to surgery as well as through postoperative days (POD) 0 to 4. Clinical data were extracted from medical records.ResultsSeveral factors were associated with higher levels of preoperative and postoperative pain. Lower preoperative average and worst pain intensity scores were associated with increases in average and worst postoperative pain from POD1 to POD4. A higher number of comorbidities, higher C-reactive protein values, and higher pain interference with function were associated with higher preoperative levels of average pain. Older age, higher fatigue levels, and higher scores on identity and emotional responses to osteoarthritis (OA) were associated with higher preoperative levels of worst pain. Lower perceived consequences of OA were associated with higher pain from POD1 to POD4. Males and patients with lower preoperative scores for average pain had higher worst pain following surgery.DiscussionPatients at higher risk for more severe postoperative pain can be identified through an assessment of pain and other risk factors identified in this study. Future research needs to test the efficacy of interventions that modify patients’ perceptions of living with OA and pain intensity before surgery on short and long term postoperative outcomes.

Efficacy and safety of fulranumab as monotherapy in patients with moderate to severe, chronic knee pain of primary osteoarthritis: a randomised, placebo- and active-controlled trial.

The efficacy and safety of monotherapy with fulranumab, a monoclonal antibody that neutralises human nerve growth factor (NGF), was evaluated compared with placebo and an active comparator, controlled-release (CR) oxycodone, in patients with moderate to severe chronic knee pain of primary osteoarthritis (OA). In this phase-2, double-blind (DB), double-dummy, placebo- and active-controlled study, patients (40-80years) were randomised (1:1:1:1) to placebo, fulranumab 3 or 9mg every 4weeks (Q4 wk), or oxycodone CR twice-daily. Primary efficacy end-point: responder rates based on percent improvement in average osteoarthritis-related pain intensity (OAPI) scores from baseline to week-12 or when Food and Drug Administration (FDA) put a clinical hold on all anti-NGF trials, whichever was earlier. Secondary efficacy end-points: average OAPI score (week-16), Western Ontario and McMaster Osteoarthritis Index Global Score and subscales (pain, physical function, stiffness), and Patient Global Assessment. As of an FDA clinical hold on all anti-NGF trials, only 196/300 patients were randomised and 33% (65/196) had completed 12weeks of the 16-week DB phase. Responders were patients who did not withdraw and whose pain improved. Responder rates were not significantly different between fulranumab treatment groups (3mgQ4wk: 71%, p=0.739; 9mgQ4wk: 80%, p=0.843) and placebo (77%), whereas, oxycodone CR (56%) had significantly lower responder rates in comparison to both fulranumab (3mgQ4wk: p=0.008; 9mgQ4wk: p=0.012) and placebo (p=0.0021). Secondary efficacy results were consistent with primary. None of the joint replacements (four in three patients) were adjudicated as rapidly progressing OA/osteonecrosis. Low sample size because of early termination make interpretation of this study difficult, but fulranumab monotherapy resulted in significantly better pain relief and function compared with oxycodoneCR (but not against placebo) and was generally well-tolerated. ClinicalTrials.gov: NCT01094262.

Predictors of Improvements in Pain Intensity in a National Cohort of Older Veterans With Chronic Pain.

Little is known about the factors associated with pain-related outcomes in older adults. In this observational study, we sought to identify patient factors associated with improvements in pain intensity in a national cohort of older veterans with chronic pain. We included 12,924 veterans receiving treatment from the Veterans Health Administration with persistently elevated numeric rating scale scores in 2010 who had not been prescribed opioids in the previous 12months. We examined: 1) percentage decrease over 12months in average pain intensity scores relative to average baseline pain intensity score; and 2) time to sustained improvement in average pain intensity scores, defined as a 30% reduction in 3-month scores compared with baseline. Average relative improvement in pain intensity scores from baseline ranged from 25% to 29%; almost two-thirds met criteria for sustained improvement during the 12-month follow-up period. In models, higher baseline pain intensity and older age were associated with greater likelihood of improvement in pain intensity, whereas Veterans Affairs service-connected disability, mental health, and certain pain-related diagnoses were associated with lower likelihood of improvement. Opioid prescription initiation during follow-up was associated with lower likelihood of sustained improvement. The findings call for further characterization of heterogeneity in pain outcomes in older adults as well as further analysis of the relationship between prescription opioids and treatment outcomes. This study identified factors associated with improvements in pain intensity in a national cohort of older veterans with chronic pain. We found that older veterans frequently show improvements in pain intensity over time, and that opioid prescriptions, mental health, and certain pain diagnoses are associated with lower likelihood of improvement.

Impact of Data Imputation Methodology on Pain Assessment over 24 Hours in a Randomized, Placebo-Controlled Study of Gabapentin Enacarbil in Patients with Neuropathic Pain Associated with Postherpetic Neuralgia

To assess the impact of gabapentin enacarbil on primary and secondary pain endpoints using three data imputation methodologies in a randomized phase II study of adult patients with postherpetic neuralgia. The primary endpoint was change from baseline to end of maintenance treatment in mean 24-hour average pain intensity score. Secondary endpoints (daytime/nighttime average pain intensity score, daytime/nighttime current pain intensity score, and daytime/nighttime worst pain intensity score) were based on daily electronic diary assessments. Comparisons of each gabapentin enacarbil dose with placebo were performed using three different statistical methodologies: last observation carried forward, baseline observation carried forward, and mixed-effect model for repeated measures. Of the 376 randomized patients, 371 were in the intent-to-treat population (gabapentin enacarbil 1,200 mg, 107; 2,400 mg, 82; 3,600 mg, 87; placebo, 95). For mean 24-hour average pain intensity score, there were statistically significant improvements from baseline to end of maintenance treatment for all gabapentin enacarbil groups vs placebo using the three analysis methods. Significant improvements were also observed for all secondary endpoints with gabapentin enacarbil 1,200 mg using the three analysis methods. Most secondary endpoints also showed improvements following treatment with gabapentin enacarbil 2,400 mg or 3,600 mg compared with placebo. Gabapentin enacarbil (1,200 mg, 2,400 mg, and 3,600 mg) was effective and well tolerated in patients with postherpetic neuralgia compared with placebo, as confirmed by three different and robust statistical methodologies.

Efficacy and tolerability of buccal buprenorphine in opioid-naive patients with moderate to severe chronic low back pain

Objectives: Buprenorphine HCl buccal film has been developed for treating chronic pain utilizing BioErodible MucoAdhesive (BEMA®) delivery technology. Buccal buprenorphine (BBUP; BelbucaTM, Endo Pharmaceuticals) was evaluated for the management of moderate to severe chronic low back pain (CLBP) requiring around-the-clock analgesia in a multicenter, double-blind, placebo-controlled, enriched-enrollment, randomized-withdrawal study in opioid-naive patients.Methods: Patients (n = 749) were titrated to a dose of BBUP (range, 150–450 µg every 12 h) that was generally well tolerated and provided adequate analgesia for ≥14 days, and then randomized to BBUP (n = 229) or placebo (n = 232), respectively. The primary efficacy variable was the change from baseline to week 12 of double-blind treatment in the mean of daily average pain intensity scores (numeric rating scale from 0 [no pain] to 10 [worst pain imaginable]).Results: Patients were experiencing moderate to severe pain at study entry: mean (SD) = 7.15 (1.05). Following titration, pain was reduced to the mild range; 2.81 (1.07). After randomization, mean (SD) pain scores increased from baseline to week 12 more with placebo (1.59 [2.04]) versus BBUP: (0.94 [1.85]) with a significant between-group difference (−0.67 [95% CI: −1.07 to −0.26]; p = 0.0012). A significantly larger percentage of patients receiving BBUP versus placebo had ≥30% pain reduction (63% vs 47%; p = 0.0012). During double-blind treatment, the most frequent adverse events (AEs) with BBUP were nausea (10%), constipation (4%) and vomiting (4%). The most common AEs with placebo were nausea (7%), upper respiratory tract infection (4%), headache (3%) and diarrhea (3%).Conclusions: These findings demonstrate the efficacy and tolerability of BBUP among opioid-naive patients requiring around-the-clock opioid treatment for CLBP.

Predictors of Response in Patients With Postherpetic Neuralgia and HIV-Associated Neuropathy Treated With the 8% Capsaicin Patch (Qutenza).

Qutenza is a high-dose capsaicin patch used to relieve neuropathic pain from postherpetic neuralgia (PHN) and HIV-associated neuropathy (HIV-AN). In clinical studies, some patients had a dramatic response to the capsaicin patch. Our objective was to determine the baseline characteristics of patients who best benefit from capsaicin patch treatment. We conducted a meta-analysis of 6 completed randomized and controlled Qutenza studies by pooling individual patient data. Sustained response was defined as>50% decrease in the mean pain intensity from baseline to weeks 2 to 12, and Complete Response as an average pain intensity score≤1 during weeks 2 to 12. Logistic regression was used to identify predictors of response and Complete Response, and subgroups of patients who respond best to the capsaicin patch. Baseline pain intensity score (BPIS)≤4 was a predictor of Sustained and Complete Response in PHN and HIV-AN patients; absence of allodynia and presence of hypoesthesia, and a McGill Pain Questionnaire (MPQ) sensory score <22 were predictors of Sustained Response in PHN patients; female sex was a predictor of Sustained and Complete Response in HIV-AN patients. Thus, characteristics associated with the highest chance of responding to the capsaicin patch were, for PHN, BPIS≤4, MPQ sensory score≤22, absence of allodynia, and presence of hypoesthesia; for HIV-AN, they were female sex and BPIS≤4. Patients with these characteristics had a statistically significantly greater chance of responding to the capsaicin patch than other patients. We identified subpopulations of PHN and HIV-AN patients likely to benefit from the capsaicin patch.