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1.  Familial contributions to self-reported sleep and pain in female twins 
Pain medicine (Malden, Mass.)  2016;17(1):33-39.
Objective
The relationship between sleep quality and pain has been studied in populations with chronic pain and non-clinical populations in experimental paradigms. Little is known about the familial contributions to this relationship. This study examines self-reported sleep quality and pain in a non-clinical sample and to explore familial (i.e., shared genetic and common family environment) confounding in those relationships.
Design
Cross-sectional.
Subjects
99 community-based female twin pairs (N = 198) with a mean age of 29 years; 72% monozygotic.
Methods
The short form McGill Pain Questionnaire (McGill), a visual analog scale (VAS), a body map, and the Pittsburgh Sleep Quality Index (PSQI) measured self-reported pain and sleep quality. Mixed model regression adjusted for age was used to examine relationships between the pain indices and PSQI in overall and within-pair models.
Results
Higher PSQI total scores were significantly associated with higher scores across the sensory (B = 0.37, p < 0.001), affective (B = 0.16, p < 0.001), total scores (B = 0.54, p < 0.001) on the McGill and the VAS (B = 2.41, p < 0.001), and number of sites with any pain on the body map (B = 0.42, p = 0.001). All of these associations were diminished and rendered non-significant in within-pair analyses that accounted for genetic and familial factors (all p’s α 0.01; Bonferroni α = 0.01).
Conclusions
These findings support an association between poor sleep quality and pain and suggest that this relationship may be confounded by shared genetic and environmental factors, which could elucidate biological mechanisms that underlie the development and maintenance of pain and sleep problems.
doi:10.1111/pme.12894
PMCID: PMC4753149  PMID: 26271474
pain; sleep; females; twins; genetics; familial factors
2.  Pain Catastrophizing Predicts Menstrual Pain Ratings in Adolescent Girls with Chronic Pain 
Pain medicine (Malden, Mass.)  2016;17(1):16-24.
Objectives
The current study aimed to explore relationships among self-reported menstrual pain ratings, acute laboratory pain, pain catastrophizing, and anxiety sensitivity in a sample of girls without pain (No Pain group) and girls with a chronic pain condition (Chronic Pain group).
Setting
A laboratory at an off-campus Medical School office building.
Subjects
Eighty-four postmenarchal girls (43 No Pain, 41 Chronic Pain) ages 10–17 participated in the study.
Methods
All participants completed self-report questionnaires assessing menstrual pain, pain catastrophizing, and anxiety sensitivity and completed a cold pressor task. Pain intensity during the task was rated on a 0 (no pain) to 10 (worst pain possible) numeric rating scale.
Results
After controlling for age, average menstrual pain ratings (without medication) were significantly correlated with cold pressor pain intensity for the No Pain group only. In the Chronic Pain group, menstrual pain ratings were significantly correlated with pain catastrophizing and anxiety sensitivity. In a multiple linear regression analysis, after controlling for age, only pain catastrophizing emerged as a significant predictor of menstrual pain ratings in the Chronic Pain group.
Conclusion
Results demonstrate differences in relationships among menstrual pain, acute laboratory pain, and psychological variables in girls with no pain compared with girls with chronic pain. In addition, pain catastrophizing may be a particularly salient factor associated with menstrual pain in girls with chronic pain that warrants further investigation.
doi:10.1111/pme.12869
PMCID: PMC4791196  PMID: 26218344
Catastrophizing; Menstrual Pain; Anxiety
3.  Shortening the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R): A Proof-of-Principle Study for Customized Computer-Based Testing 
Pain medicine (Malden, Mass.)  2015;16(12):2344-2356.
Background
The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) is a 24-item self-report instrument that was developed to aid providers in predicting aberrant medication-related behaviors among chronic pain patients. Although the SOAPP-R has garnered widespread use, certain patients may be dissuaded from taking it because of its length. Administrative barriers associated with lengthy questionnaires further limit its utility.
Objective
To investigate the extent to which two techniques for computer-based administration (curtailment and stochastic curtailment) reduce the average test length of the SOAPP-R without unduly affecting sensitivity and specificity.
Design
Retrospective study
Setting
Pain management centers
Subjects
Four hundred and twenty-eight chronic non-cancer pain patients
Methods
Subjects had taken the full-length SOAPP-R and been classified by the Aberrant Drug Behavior Index (ADBI) as having engaged or not engaged in aberrant medication-related behavior. Curtailment and stochastic curtailment were applied to the data in post-hoc simulation. Sensitivity and specificity with respect to the ADBI, as well as average test length, were computed for the full-length test, curtailment, and stochastic curtailment.
Results
The full-length SOAPP-R exhibited a sensitivity of 0.745 and a specificity of 0.671 for predicting the ADBI. Curtailment reduced the average test length by 26% while exhibiting the same sensitivity and specificity as the full-length test. Stochastic curtailment reduced the average test length by as much as 65% while always exhibiting sensitivity and specificity for the ADBI within 0.035 of those of the full-length test.
Conclusions
Curtailment and stochastic curtailment have potential to improve the SOAPP-R’s efficiency in computer-based administrations.
doi:10.1111/pme.12864
PMCID: PMC4706778  PMID: 26176496
Chronic Pain; Substance Abuse; Opioids; SOAPP-R; Respondent Burden; Risk Stratification
4.  Pain Duration and Resolution Following Surgery: An Inception Cohort Study 
Pain medicine (Malden, Mass.)  2015;16(12):2386-2396.
Objective
Preoperative determinants of pain duration following surgery are poorly understood. We identified preoperative predictors of prolonged pain after surgery in a mixed surgical cohort.
Methods
We conducted a prospective longitudinal study of patients undergoing mastectomy, lumpectomy, thoracotomy, total knee replacement, or total hip replacement. We measured preoperative psychological distress and substance use, and then measured pain and opioid use after surgery until patients reported the cessation of both opioid consumption and pain. The primary endpoint was time to opioid cessation, and those results have been previously reported. Here we report preoperative determinants of time to pain resolution following surgery in Cox proportional hazards regression.
Results
Between January 2007 and April 2009 we enrolled 107 of 134 consecutively approached patients undergoing the aforementioned surgical procedures. In the final multivariate model, preoperative self-perceived risk of addiction predicted more prolonged pain. Unexpectedly, anxiety sensitivity predicted more rapid pain resolution after surgery. Each one-point increase (on a four point scale) of self-perceived risk of addiction was associated with a 38% (95% CI 3 - 61) reduction in the rate of pain resolution (p= 0.04). Furthermore, higher anxiety sensitivity was associated with an 89% (95% CI 23–190) increased rate of pain resolution (p=0.004).
Conclusions
Greater preoperative self-perceived risk of addiction, and lower anxiety sensitivity predicted a slower rate of pain resolution following surgery. Each of these factors was a better predictor of pain duration than preoperative depressive symptoms, PTSD symptoms, past substance use, fear of pain, gender, age, preoperative pain, or preoperative opioid use.
doi:10.1111/pme.12842
PMCID: PMC4706803  PMID: 26179223
5.  Deconstructing Chronic Low Back Pain in the Older Adult: Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment 
Pain medicine (Malden, Mass.)  2015;16(11):2098-2108.
Objective
To present the fourth in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of twelve important contributors to pain and disability in older adults with CLBP. This article focuses on depression.
Methods
The evaluation and treatment algorithm, a table articulating the rationale for the individual algorithm components, and stepped-care drug recommendations were developed using a modified Delphi approach. The Principal Investigator, a three-member content expert panel, and a nine-member primary care panel were involved in the iterative development of these materials. The algorithm was developed keeping in mind medications and other resources available within Veterans Health Administration (VHA) facilities. As panelists were not exclusive to the VHA, the materials can be applied in both VHA and civilian settings. The illustrative clinical case was taken from one of the contributor’s clinical practice.
Results
We present an algorithm and supportive materials to help guide the care of older adults with depression, an important contributor to CLBP. The case illustrates an example of a complex clinical presentation in which depression was an important contributor to symptoms and disability in an older adult with CLBP.
Conclusions
Depression is common and should be evaluated routinely in the older adult with CLBP so that appropriately targeted treatments can be planned and implemented.
doi:10.1111/pme.12935
PMCID: PMC4821461  PMID: 26539754
Aged; Assessment; Depression; Chronic Pain; Elderly; Low Back Pain; Primary Care
6.  The Subjective Experience of Pain: an FMRI Study of Percept-related Models and Functional Connectivity 
Pain medicine (Malden, Mass.)  2015;16(11):2121-2133.
Objective
Previous work suggests that the perception of pain is subjective and dependent on individual differences in physiological, emotional and cognitive states. Functional magnetic resonance imaging (FMRI) studies have utilized both stimulus-related (nociceptive properties) and percept-related (subjective experience of pain) models to identify the brain networks associated with pain. Our objective was to identify the network involved in processing subjective pain during cold stimuli.
Methods
The current FMRI study directly contrasted a stimulus-related model with a percept-related model during blocks of cold pain stimuli in healthy adults. Specifically, neuronal activation was modelled as a function of changes in stimulus intensity versus as a function of increasing/decreasing levels of subjective pain corresponding to changes in pain ratings. In addition, functional connectivity analyses were conducted to examine intrinsic correlations between three proposed sub-networks (sensory/discriminative, affective/motivational, and cognitive/evaluative) involved in pain processing.
Results
The percept-related model captured more extensive activation than the stimulus-related model and demonstrated an association between higher subjective pain and activation in expected cortical (DLPFC, VLPFC, insula, ACC extending into preSMA) and subcortical (thalamus, striatum) areas. Moreover, connectivity results supported the posited roles of dACC and insula as key relay sites during neural processing of subjective pain. In particular, anterior insula appeared to link sensory/discriminative regions with regions in the other sub-networks, and dACC appeared to serve as a hub for affective/motivational, cognitive/evaluative, and motor sub-networks.
Conclusions
Using a percept-related model, brain regions involved in the processing of subjective pain during the application of cold stimuli were identified. Connectivity analyses identified linkages between key sub-networks involved in processing subjective pain.
doi:10.1111/pme.12785
PMCID: PMC4653099  PMID: 25989475
pain; ratings; percept-related; connectivity; FMRI
7.  Deconstructing Chronic Low Back Pain in the Older Adult – Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment: Part III: Fibromyalgia Syndrome 
Pain medicine (Malden, Mass.)  2015;16(9):1709-1719.
Objective
To present the third in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of twelve important contributors to pain and disability in older adults with CLBP. This article focuses on fibromyalgia syndrome (FMS).
Methods
A modified Delphi approach was used to create the evaluation and treatment algorithm, the table discussing the rationale behind each of the algorithm components, and the stepped-care drug recommendations. The team involved in the creation of these materials consisted of a principal investigator, a 5-member content expert panel, and a 9-member primary care panel. The evaluation and treatment recommendations were based on availability of medications and other resources within the Veterans Health Administration (VHA) facilities. However, non-VHA panelists were also involved in the development of these materials, which can be applied to both VA and civilian settings. The illustrative clinical case was taken from the clinical practice of the principal investigator.
Results
Following expert consultations and a review of the literature, we developed an evaluation and treatment algorithm with supporting materials to aid in the care of older adults with CLBP who have concomitant FMS. A case is presented that demonstrates the complexity of pain evaluation and management in older patients with CLBP and concomitant FMS
Conclusions
Recognition of FMS as a common contributor to CLBP in older adults and initiating treatment targeting both FMS and CLBP will lead to improved outcomes in pain and disability.
doi:10.1111/pme.12863
PMCID: PMC5066871  PMID: 26272644
8.  Chronic pain in HIV-infected patients: relationship to depression, substance use, and mental health and pain treatment 
Pain medicine (Malden, Mass.)  2015;16(10):1870-1881.
Objective
Since the advent of highly active antiretroviral therapy (HAART), HIV has become a chronic disease for most individuals in developed countries. Chronic pain is a common occurrence for HIV –infected patients and has an impact on quality of life and antiretroviral adherence. The objective of this study was to examine relationships between chronic pain and depression, substance use, mental health treatment, and pain treatment in HIV-infected patients.
Design
Cross-sectional study.
Setting
Three primary care sites where HIV+ patients receive treatment.
Subjects
238 HIV-infected primary care patients.
Methods
We collected self-report and chart-review information on demographics, HIV clinical status, chronic pain, depression, substance use, mental health treatment, and pain treatment. We collected data between October 2012 and November 2013.
Results
Of the patients enrolled in this study, 107 reported no chronic pain, 24 reported mild chronic pain, and 107 reported moderate-severe chronic pain. Participants in the moderate-severe pain group were more likely to have high levels of depressive symptoms than those in the no chronic pain group. Similarly, there was a significant relationship between chronic pain status and interference with life activities due to pain. Participants with moderate-severe chronic pain were more likely to be taking an antidepressant medication than those with mild chronic pain, and more likely to be taking a prescription opioid than the other two groups. We did not find a significant relationship between problematic substance use and chronic pain status.
Conclusions
Despite pharmacologic treatment, moderate-severe chronic pain and elevated depression symptoms are common among HIV-infected patients and frequently co-occur.
doi:10.1111/pme.12799
PMCID: PMC4486324  PMID: 26119642
HIV; chronic pain; depression
9.  Opioid Therapy and Sleep Disorders: Risks and Mitigation Strategies 
Pain medicine (Malden, Mass.)  2015;16(0 1):S22-S26.
Objective
Patients with chronic pain frequently experience concomitant sleep disorders. There has been controversy on whether opioids have a beneficial or deleterious effect on sleep quality, duration and efficiency. There is also concern regarding the association between chronic opioid therapy and sleep disordered breathing and the increased risk for unintentional opioid related overdose. This article provides a narrative review of the literature on the effect of opioids on sleep disorders and discusses risk assessment and mitigation strategies.
Design
A narrative review of the current literature on the effect of prescription opioids on sleep quality and efficiency, the relationship between opioids and sleep disorders and potential risk factors in patients with chronic pain.
Results
There is conflicting evidence regarding the benefit of opioids in improving sleep quality, duration and efficiency with several studies and reviews suggesting a beneficial effect of opioids on sleep and other studies demonstrating the opioids can cause sleep disturbance leading to hyperalgesia. There was credible evidence of a strong relationship between opioids and sleep disordered breathing with noted risk factors including use of methadone, high opioid dosing (> 200 mg MED) and combining opioids with benzodiazepines.
Conclusions
Further research is required to elucidate the effect of prescription opioids on sleep quality and pain intensity and the risks associated with opioids and sleep disordered breathing. The risk of sleep disordered breathing should be routinely assessed in patients on chronic opioid therapy.
doi:10.1111/pme.12910
PMCID: PMC4608386  PMID: 26461072
Opioid therapy; chronic pain; sleep disordered breathing; methadone
10.  Racial disparities across provider specialties in opioid prescriptions dispensed to Medicaid beneficiaries with chronic non-cancer pain 
Pain medicine (Malden, Mass.)  2014;16(4):633-640.
Objective
Chronic pain affects both psychological and physical functioning, and is responsible for more than $60 billion in lost productivity annually in the United States. Although previous studies have demonstrated racial disparities in opioid treatment, there is little evidence regarding disparities in treatment of chronic non-cancer pain (CNCP) and the role of physician specialty.
Design
A retrospective cohort study.
Setting
We analyzed North Carolina Medicaid claims data, from July 1, 2009 to May 31, 2010, to examine disparities by different provider specialties in beneficiaries dispensed prescriptions for opioids.
Subjects
The population included White and Black North Carolina Medicaid beneficiaries with CNCP (n=75,458).
Methods
We used bivariate statistics and logistic regression analysis to examine race-based discrepancies in opioid prescribing by physician specialty.
Results
Compared to White beneficiaries with CNCP (n=49,197), Black beneficiaries (n=26,261) were less likely [OR 0.91 (CI: 0.88–0.94)] to fill an opioid prescription. Our hypothesis was partially supported: we found that race-based differences in beneficiaries dispensed opioid prescriptions were more prominent in certain specialties. In particular, these differences were most salient among patients of specialists in obstetrics and gynecology [OR 0.78 (CI: 0.67–0.89)] and internal medicine [OR 0.86 (CI: 0.79–0.92)], as well as general practitioners/family medicine physicians [OR 0.91 (CI: 0.85–0.97)].
Conclusions
Our findings suggest that, in our study population, Black beneficiaries with CNCP are less likely than Whites to fill prescriptions for opioid analgesics as a function of their provider’s specialty. Although race-based differences in patients filling opioid prescriptions have been noted in previous studies, this is the first study that clearly demonstrates these disparities by provider specialty.
doi:10.1111/pme.12555
PMCID: PMC5012901  PMID: 25287703
11.  Neurostimulation for Treatment of Migraine and Cluster Headache 
Pain medicine (Malden, Mass.)  2015;16(9):1827-1834.
Objective
The objective of this narrative review was to summarize the current state of neurostimulation therapies for the treatment of migraine and/or cluster.
Methods
For this narrative review, publications were identified by searching PubMed using the search terms “migraine” or “cluster” combined with “vagal nerve stimulation”, “transcranial magnetic stimulation”, “supraorbital nerve stimulation”, “sphenopalatine ganglion stimulation”, “occipital nerve stimulation”, “deep brain stimulation”, “neurostimulation”, or “neuromodulation”. Publications were chosen based upon the quality of data that were provided and their relevance to the chosen topics of interest for this review. Reference lists of chosen articles and the authors own files were used to identify additional publications. Current clinical trials were identified by searching clinicaltrials.org.
Results and Conclusions
Neurostimulation of the vagal nerve, supraorbital nerve, occipital nerve and sphenopalatine ganglion, transcranial magnetic stimulation, and deep brain stimulation have been investigated for the treatment of migraine and/or cluster. Whereas invasive methods of neurostimulation would be reserved for patients with very severe and treatment refractory migraine or cluster, non-invasive methods of stimulation might serve as useful adjuncts to more conventional therapies. Currently, transcutaneous supraorbital nerve stimulation is FDA approved and commercially available for migraine prevention and transcranial magnetic stimulation is FDA approved for the treatment of migraine with aura. The potential utility of each type of neurostimulation has yet to be completely defined.
doi:10.1111/pme.12792
PMCID: PMC4572909  PMID: 26177612
Migraine; Cluster Headache; Neurostimulation; Vagal Nerve Stimulation; Deep Brain Stimulation; Transcranial Magnetic Stimulation; Occipital Nerve Stimulation; Transcutaneous Supraorbital Nerve Stimulation; Sphenopalatine Ganglion Stimulation
12.  Acute Pain Medicine in the United States: A Status Report 
Pain medicine (Malden, Mass.)  2015;16(9):1806-1826.
Background
Consensus indicates that a comprehensive, multimodal, holistic approach is foundational to the practice of acute pain medicine (APM), but lack of uniform, evidence-based clinical pathways leads to undesirable variability throughout U. S. healthcare systems. Acute pain studies are inconsistently synthesized to guide educational programs. Advanced practice techniques involving regional anesthesia assume the presence of a physician-led, multidisciplinary acute pain service, which is often unavailable or inconsistently applied. This heterogeneity of educational and organizational standards may result in unnecessary patient pain and escalation of healthcare costs.
Methods
A multidisciplinary panel was nominated through the Acute Pain Medicine Shared Interest Group (APMSIG) of the American Academy of Pain Medicine (AAPM). The panel met in Chicago, Illinois, in July 2014, to identify gaps and set priorities in APM research and education.
Results
The panel identified 3 areas of critical need: 1) an open-source acute pain data registry and clinical support tool to inform clinical decision making and resource allocation and to enhance research efforts; 2) a strong professional APM identity as an accredited subspecialty; and 3) educational goals targeted toward third-party payers, hospital administrators, and other key stakeholders to convey the importance of APM.
Conclusion
This report is the first step in a 3-year initiative aimed at creating conditions and incentives for the optimal provision of APM services to facilitate and enhance the quality of patient recovery after surgery, illness, or trauma. The ultimate goal is to reduce the conversion of acute pain to the debilitating disease of chronic pain.
PMCID: PMC4634553  PMID: 26535424
Acute Pain; Delivery of Healthcare; Medical Informatics; Anesthesiology; Research; Education
13.  One Month of Oral Morphine Decreases Gray Matter Volume in the Right Amygdala of Individuals with Low Back Pain: Confirmation of Previously Reported Magnetic Resonance Imaging Results 
Pain medicine (Malden, Mass.)  2015;17(8):1497-1504.
Objective
Prolonged exposure to opioids is known to produce neuroplastic changes in animals; however, few studies have investigated the effects of short-term prescription opioid use in humans. A previous study from our laboratory demonstrated a dosage-correlated volumetric decrease in the right amygdala of participants administered oral morphine daily for 1 month. The purpose of this current study was to replicate and extend the initial findings.
Methods
Twenty-one participants with chronic low back pain were enrolled in this double-blind, placebo-controlled study. Participants were randomized to receive daily morphine (n = 11) or a matched placebo (n = 10) for 1 month. High-resolution anatomical images were acquired immediately before and after the treatment administration period. Morphological gray matter changes were investigated using tensor-based morphometry, and significant regions were subsequently tested for correlation with morphine dosage.
Results
Decreased gray matter volume was observed in several reward- and pain-related regions in the morphine group, including the bilateral amygdala, left inferior orbitofrontal cortex, and bilateral pre-supplementary motor areas. Morphine administration was also associated with significant gray matter increases in cingulate regions, including the mid cingulate, dorsal anterior cingulate, and ventral posterior cingulate.
Conclusions
Many of the volumetric increases and decreases overlapped spatially with the previously reported changes. Individuals taking placebo for 1 month showed neither gray matter increases nor decreases. The results corroborate previous reports that rapid alterations occur in reward-related networks following short-term prescription opioid use.
doi:10.1093/pm/pnv047
PMCID: PMC4921346  PMID: 26814280
Opioids; Magnetic Resonance Imaging; Tensor-Based Morphometry
14.  Effects of transcranial direct current stimulation (tDCS) on pain distress tolerance: a preliminary study 
Pain medicine (Malden, Mass.)  2015;16(8):1580-1588.
Objective
Pain remains a critical medical challenge. Current treatments target nociception without addressing affective symptoms. Medically intractable pain is sometimes treated with cingulotomy or deep brain stimulation to increase tolerance of pain-related distress. Transcranial direct current stimulation (tDCS) may noninvasively modulate cortical areas related to sensation and pain representations. The present study aimed to test the hypothesis that cathodal (“inhibitory”) stimulation targeting left dorsal anterior cingulate cortex (dACC) would increase tolerance to distress from acute painful stimuli versus anodal stimulation.
Methods
Forty healthy volunteers received both anodal and cathodal stimulation. During stimulation, we measured pain distress tolerance with three tasks: pressure algometer, cold pressor, and breath holding. We measured pain intensity with a visual-analog scale before and after each task.
Results
Mixed ANOVA revealed that mean cold pressor tolerance tended to be higher with cathodal versus anodal stimulation (p = 0.055) for participants self-completing the task. Pressure algometer (p = 0.81) and breath holding tolerance (p = 0.19) did not significantly differ. The pressure algometer exhibited a statistically significant order effect irrespective of stimulation polarity (all p < 0.008). Pain intensity ratings increased acutely after cold pressor and pressure algometer tasks (both p < 0.01), but not after breath holding (p = 0.099). Cold pressor pain ratings tended to rise less after cathodal versus anodal tDCS (p = 0.072).
Conclusions
Although our primary results were nonsignificant, there is a preliminary suggestion that cathodal tDCS targeting left dACC may increase pain distress tolerance to cold pressor. Pressure algometer results are consistent with task-related sensitization. Future studies are needed to refine this novel approach for pain neuromodulation.
doi:10.1111/pme.12798
PMCID: PMC4545473  PMID: 26115372
neuromodulation; transcranial direct current stimulation; tDCS; pain; distress tolerance; noninvasive
15.  Pilot Study of Exercise Therapy on Painful Diabetic Peripheral Neuropathy 
Pain medicine (Malden, Mass.)  2015;16(8):1482-1489.
Objective
Painful diabetic peripheral neuropathy (DPN) is a common complication of diabetes. While the beneficial effect of exercise on diabetes is well established, its effect specifically on painful DPN has not been thoroughly explored. The objective of this pilot study was to examine the effect of aerobic exercise on pain in people with DPN.
Methods
Fourteen sedentary individuals (mean age 57±5.11 years) with painful DPN were enrolled in a 16-week, supervised aerobic exercise program. The Brief Pain Inventory-Diabetic Peripheral Neuropathy (BPI-DPN) was used to assess pain intensity (worst, least, average, now) and pain interference with daily life (activity, mood, walk, normal work, relationship, sleep, enjoyment of life) pre- and post -intervention. Body mass index (BMI), maximum oxygen uptake (VO2max), hemoglobin A1c (HbA1c), and blood pressure were also measured pre-and post-intervention as secondary outcomes of interest.
Results
Significant reductions in pain interference were observed with walking (4.93±3.03 pre to 3.29±2.89 post, p=0.016), normal work (5.39±3.32 pre to 3.79±3.04 post, p=0.032), relationship with others (3.96±3.53 pre to 1.29±1.27 post, p=0.006), sleep (5.11±3.04 pre to 3.5±3.03 post, p=0.02), and the overall pain interference (4.65±2.70 pre to 2.97±2.22 post, p=0.013) following the intervention; however, there was no change in pain intensity. VO2max increased significantly post-intervention (16.02±3.84ml/kg/min pre to 17.18±4.19ml/kg/min, p=0.028), while BMI, HbA1c, and blood pressure remained unchanged.
Conclusion
These preliminary results suggest that perceived pain interference may be reduced following an aerobic exercise intervention among people with painful DPN, without a change in pain intensity. Further validation by a RCT is needed.
doi:10.1111/pme.12743
PMCID: PMC4673891  PMID: 25800666
diabetic peripheral neuropathy; exercise; pain; pain interference
16.  Composite Pain Index (CPI): Reliability, Validity, and Sensitivity of a Patient-Reported Outcome for Research 
Pain medicine (Malden, Mass.)  2015;16(7):1341-1348.
Objective
A single score that represents the multidimensionality of pain would be an innovation for patient-reported outcomes. Our aim was to determine the reliability, validity, and sensitivity of the Composite Pain Index.
Design
Methodological analysis of data from a randomized controlled, pretest/posttest education-based intervention study.
Setting
The study was conducted in outpatient oncology clinics.
Subjects
The 176 subjects had pain, were 52 ± 12.5 years on average, 63% were female, and 46% had stage IV cancers.
Methods
We generated the Composite Pain Index from pain location, intensity, quality, and pattern scores measured with an electronic version of Melzack’s McGill Pain Questionnaire.
Results
The internal consistency values for the individual scores comprising the Composite Pain Index were adequate (.71 baseline, .69 posttest). Principal components analysis extracted one factor with an eigenvalue of 2.17 with explained variance of 54% at baseline and replicated the one factor with an eigenvalue of 2.11 at posttest. The factor loadings for location, intensity, quality, and pattern were .65, .71, .85, and .71 respectively (baseline) and .59, .81, .84, and .63 respectively (posttest). The Composite Pain Index was sensitive to an education intervention effect.
Conclusions
Findings support the Composite Pain Index as a score that integrates the multidimensional pain experience in people with cancer. It could be used as a patient-reported outcome measure to quantify the complexity of pain in clinical research and population studies of cancer pain and studied for relevance in other pain populations.
doi:10.1111/pme.12703
PMCID: PMC4504760  PMID: 25712169
17.  Teaching a Machine to Feel Postoperative Pain: Combining High-Dimensional Clinical Data with Machine Learning Algorithms to Forecast Acute Postoperative Pain 
Pain medicine (Malden, Mass.)  2015;16(7):1386-1401.
Background
Given their ability to process highly dimensional datasets with hundreds of variables, machine learning algorithms may offer one solution to the vexing challenge of predicting postoperative pain.
Methods
Here, we report on the application of machine learning algorithms to predict postoperative pain outcomes in a retrospective cohort of 8071 surgical patients using 796 clinical variables. Five algorithms were compared in terms of their ability to forecast moderate to severe postoperative pain: Least Absolute Shrinkage and Selection Operator (LASSO), gradient-boosted decision tree, support vector machine, neural network, and k-nearest neighbor, with logistic regression included for baseline comparison.
Results
In forecasting moderate to severe postoperative pain for postoperative day (POD) 1, the LASSO algorithm, using all 796 variables, had the highest accuracy with an area under the receiver-operating curve (ROC) of 0.704. Next, the gradient-boosted decision tree had an ROC of 0.665 and the k-nearest neighbor algorithm had an ROC of 0.643. For POD 3, the LASSO algorithm, using all variables, again had the highest accuracy, with an ROC of 0.727. Logistic regression had a lower ROC of 0.5 for predicting pain outcomes on POD 1 and 3.
Conclusions
Machine learning algorithms, when combined with complex and heterogeneous data from electronic medical record systems, can forecast acute postoperative pain outcomes with accuracies similar to methods that rely only on variables specifically collected for pain outcome prediction.
doi:10.1111/pme.12713
PMCID: PMC4504764  PMID: 26031220
Machine Learning; Algorithm; Postoperative Pain; Pain Prediction
18.  Unresolved pain interference among colorectal cancer survivors: Implications for patient care and outcomes 
Pain medicine (Malden, Mass.)  2015;16(7):1410-1425.
Objective
Using a large sample of colorectal cancer (CRC) survivors we 1) describe pain interference (PI) prevalence across the cancer continuum; 2) identify demographic and clinical factors associated with PI and changes in PI; and 3) examine PI’s relationship with survivors’ job changes.
Methods
CRC participants of the Cancer Care Outcomes Research and Surveillance Consortium completed surveys during the initial phase of care (baseline, <1 year, n=2,961) and follow-up (about 1-year post-diagnosis, n=2,303). PI was measured using the SF-12 item. Multiple logistic regression was used to identify predictors of PI. Model 1 evaluated moderate/high PI at baseline, Model 2 evaluated new/continued/increasing PI post-diagnosis follow-up, and Model 3 restricted to participants with baseline PI (N=603) and evaluated predictors of equivalent/increasing PI. Multivariable logistic regression was also used to examine whether PI predicted job change.
Results
At baseline and follow-up, 24.7% and 23.7% of participants reported moderate/high PI, respectively. Among those with baseline PI, 46% had equivalent/increasing PI at follow-up. Near diagnosis and at follow-up, female gender, comorbidities, depression, chemotherapy and radiation were associated with moderate/high PI while older age was protective of PI. Pulmonary disease and heart failure comorbidities were associated with equivalent/increasing PI. PI was significantly associated with no longer having a job at follow-up among employed survivors.
Conclusion
Almost half of survivors with PI during the initial phase of care had continued PI into post-treatment. Comorbidities, especially cardiovascular and pulmonary conditions, contributed to continued PI. PI may be related to continuing normal activities, i.e., work, after completed treatment.
doi:10.1111/pme.12727
PMCID: PMC4504768  PMID: 25799885
19.  Dynamic pain phenotypes are associated with spinal cord stimulation-induced reduction in pain: A repeated measures observational pilot study 
Pain medicine (Malden, Mass.)  2015;16(7):1349-1360.
Objective
Spinal Cord Stimulation (SCS) has become a widely used treatment option for a variety of pain conditions. Substantial variability exists in the degree of benefit obtained from SCS and patient selection is a topic of expanding interest and importance. However, few studies have examined the potential benefits of dynamic Quantitative Sensory Testing (QST) to develop objective measures of SCS outcomes or as a predictive tool to help patient selection. Psychological characteristics have been shown to play an important role in shaping individual differences in the pain experience and may aid in predicting responses to SCS. Static laboratory pain-induction measures have also been examined in their capacity for predicting SCS outcomes.
Methods
The current study evaluated clinical, psychological and laboratory pain measures at baseline, during trial SCS lead placement, as well as one month and three months following permanent SCS implantation in chronic pain patients who received SCS treatment. Several QST measures were conducted, with specific focus on examination of dynamic models (central sensitization and conditioned pain modulation [CPM]) and their association with pain outcomes three months post SCS implantation.
Results
Results suggest few changes in QST over time. However, central sensitization and CPM at baseline were significantly associated with clinical pain at three months following SCS implantation, controlling for psycho/behavioral factors and pain at baseline. Specifically, enhanced central sensitization and reduced CPM were associated with less self-reported pain three months following SCS implantation.
Conclusions
These findings suggest a potentially important role for dynamic pain assessment in individuals undergoing SCS, and hint at potential mechanisms through which SCS may impart its benefit.
doi:10.1111/pme.12732
PMCID: PMC4504785  PMID: 25800088
Spinal Cord Stimulation; Clinical Pain; Laboratory Pain; Quantitative Sensory Testing; Central Sensitization; Conditioned Pain Modulation; Psychosocial Factors
20.  Barriers to chronic pain measurement: a qualitative study of patient perspectives 
Pain medicine (Malden, Mass.)  2015;16(7):1256-1264.
Objective
Preliminary evidence suggests that chronic pain patients complete pain intensity measures using idiosyncratic methods. Our objective was to understand these methods and how they might impact the psychometric properties of the instruments.
Design
A qualitative focus-group based study.
Setting
An academic center in New York City
Subjects
Outpatients (n=36) with chronic low back pain, or neuropathic pain due to diabetes or HIV.
Methods
Participants were divided into three focus groups based on their pain condition, and asked to discuss pain intensity measures (visual analog and numeric rating scales for average pain over 24 hours; Brief Pain Inventory; and McGill Pain Questionnaire). Audio-recordings were transcribed and analyzed using an inductive thematic method.
Results
We discovered four main themes, and five sub-themes: 1) doubt that pain can be accurately measured (sub-themes: pain measurement is influenced by things other than pain, the numbers used to rate pain do not have an absolute meaning, and preference for pain intensity ratings “in the middle” of the scale); 2) confusion regarding the definition of pain; 3) what experiences to use as referents (sub-themes: appropriate comparator experiences and the interpretation of the anchors of the scale); and 4) difficulty averaging pain.
Conclusions
The themes discovered suggest that patients include sensations and experiences other than pain intensity in their ratings, experience the rating of pain as a comparative task, and do not use the scale in a linear manner. These themes are relevant to understanding the validity and scale properties of commonly used pain intensity measures.
doi:10.1111/pme.12717
PMCID: PMC4504818  PMID: 25688752
measurement; chronic pain; diabetic neuropathy; HIV; neuropathic pain; low back pain
21.  Minority Aging and Endogenous Pain Facilitatory Processes 
Pain medicine (Malden, Mass.)  2015;17(6):1037-1048.
Objective
The aim of the current study was to examine the relationships among age, ethnicity, and endogenous pain facilitation using temporal summation (TS) responses to mechanical and heat stimuli.
Design
The present study assessed hyperalgesia and pain facilitation to thermal and mechanical stimuli at the knee and distal sites in 98 pain-free men and women. Participants were drawn from two ethnic (African-Americans, AA; and non-Hispanic whites, NHW) and age groups (19-35 and 45-85).
Results
Significant main effects of ethnicity were demonstrated for both mechanical and heat modalities (all p’s≤0.05), suggesting that AA participants, relative to NHW counterparts, demonstrated enhanced hyperalgesia. Age differences (older > younger) in hyperalgesia were found in mechanical pain ratings only. Results indicated that mechanical pain ratings significantly increased from first to maximal pain as a function of both age group and ethnicity (all p’s≤0.05), and a significant ethnicity by age interaction for TS of mechanical pain was found at the forearm (p<0.05) and trended towards significance at the knee (p=0.071). Post-hoc tests suggested that results were primarily driven by the older AA participants, who demonstrated the greatest mechanical TS. Additionally, evidence of differences in heat TS due to both ethnicity alone (all p’s≤0.05) and minority aging was also found.
Conclusions
This study provides evidence suggesting that older AAs demonstrate enhanced pain facilitatory processes, which is important because this group may be at increased risk for development of chronic pain. These results underscore the necessity of testing pain modulatory mechanisms when addressing questions related to pain perception and minority aging.
doi:10.1093/pm/pnv014
PMCID: PMC4896853  PMID: 26814250
Pain; Hyperalgesia; Facilitation; Ethnicity; Aging; Minority Aging
22.  How, why, and for whom do emergency medicine providers use Prescription Drug Monitoring Programs? 
Pain medicine (Malden, Mass.)  2015;16(6):1122-1131.
Objective
The prescription opioid epidemic is currently responsible for the greatest number of unintentional deaths in the United States. One potential strategy for decreasing this epidemic is implementation of state-based Prescription Drug Monitoring Programs (PDMPs), which are designed for providers to identify patients who “doctor shop” for prescriptions. Emergency medicine physicians are some of the most frequent PDMP users and opioid prescribers, but little is known about how they actually use PDMPs, for which patients, and for what reasons.
Methods
We conducted and transcribed semi-structured qualitative interviews with 61 physicians at a national academic conference in October 2012. Deidentified transcripts were entered into QSR NVivo 10.0, coded, and analyzed for themes using modified grounded theory.
Results
There is variation in pattern and frequency of PDMP access by emergency physicians. Providers rely on both structural characteristics of the PDMP, such as usability, and also their own clinical gestalt impression when deciding to use PDMPs for a given patient encounter. Providers use the information in PDMPs to alter clinical decisions and guide opioid prescribing patterns. Physicians describe alternative uses for the databases, such as improving their ability to facilitate discussions on addiction and provide patient education.
Conclusion
PDMPs are used for multiple purposes, including identifying opioid misuse and enhancing provider-patient communication. Given variation in practice, standards may help direct indication and manner of physician use. Steps to minimize administrative barriers to PDMP access are warranted. Finally, alternative PDMP uses should be further studied to determine their appropriateness and potentially expand their role in clinical practice.
doi:10.1111/pme.12700
PMCID: PMC4478227  PMID: 25688454
prescription opioids; prescription monitoring programs; emergency care; healthcare providers
23.  Pain and Psychological Well-Being among People with Dementia in Long-Term Care 
Pain medicine (Malden, Mass.)  2015;16(6):1083-1089.
Objective
To examine the relationship between self-reported pain and psychological well-being of people with dementia (PWD) living in residential long-term care as indicated by displays of observed emotional expression over the daytime period.
Design
Secondary analysis using repeated measures of self-report and observational data.
Setting and subjects
A total of 177 PWD were included from 17 nursing homes and six assisted living facilities in Michigan and Pennsylvania.
Methods
Negative emotional expression was used as an indicator of reduced psychological well-being. Pain was assessed through PWD's response to a question about presence of pain obtained at each observation. Cognitive impairment was assessed using the Mini-Mental Status Examination (MMSE). Linear mixed models were used that accounted for correlation of negative emotional expression measurements over time for each participant and between participants within the same facility.
Results
Among 171 participants who were able to express their pain, 44% of PWD reported pain once or more during the daytime period. Severity of cognitive impairment was related to expression of negative emotion. PWD with pain displayed more negative emotional expression than PWD without pain.
Conclusions
Routine pain assessment is feasible among PWD with moderate to severe dementia and positive report of pain is associated with greater observed negative emotional expression, an indicator of reduced psychological well-being. Improving pain management holds potential for enhancing psychological well-being among PWD living in residential long-term care.
doi:10.1111/pme.12739
PMCID: PMC4478238  PMID: 25800276
pain; psychological well-being; dementia
24.  Acupuncture Provides Short-term Pain Relief for Patients in a Total Joint Replacement Program 
Pain medicine (Malden, Mass.)  2015;16(6):1195-1203.
Objective
Given the risks of opioid medications, non-pharmacological strategies should be considered for total joint replacement patients. We investigated acupuncture as an adjunct therapy for post-surgical pain management in a total joint replacement program by examining which total hip and knee replacement patients elected to receive acupuncture and the effect of acupuncture on short-term pain.
Design
A total joint replacement program using fast-track physiotherapy offered elective post-surgical acupuncture to all patients, at no additional cost, as an adjunct therapy to opioids for pain management.
Setting
The Joint Replacement Center at Abbott Northwestern Hospital, a 630-bed teaching and specialty hospital in Minneapolis, Minnesota from 2010 to 2012.
Subjects
Our sample included 2,500 admissions of total hip and total knee replacement patients.
Methods
Self-reported pain was assessed before and after acupuncture using a 0-10 scale and categorized as none/mild (0-4) and moderate/severe pain (5-10).
Results
Seventy-five percent of admissions included acupuncture. Women (Odds Ratio: 1.48, 95% Confidence Interval: 1.22, 1.81) had higher odds of receiving acupuncture compared to men, and non-white patients (Odds Ratio: 0.55, 95% Confidence Interval: 0.39, 0.78) had lower odds of receiving acupuncture compared to white patients. Average short-term pain reduction was 1.91 points (95% Confidence Interval: 1.83, 1.99), a 45% reduction from the mean pre-pain score. Forty-one percent of patients reported moderate/severe pain prior to receiving acupuncture, while only 15% indicated moderate/severe pain after acupuncture.
Conclusions
Acupuncture may be a viable adjunct to pharmacological approaches for pain management after total hip or total knee replacement.
doi:10.1111/pme.12685
PMCID: PMC4478153  PMID: 25586769
Acupuncture; total joint replacement; integrative medicine; post-operative pain; multi-modal pain management
25.  Impact of Peripheral Nerve Block With Low Dose Local Anesthetics on Analgesia and Functional Outcomes Following Total Knee Arthroplasty: A Retrospective Study 
Pain medicine (Malden, Mass.)  2014;16(5):998-1006.
Objective
While the safety and efficacy of peripheral nerve blocks for postoperative pain management has been established in several well controlled prospective trials, the local anesthetic (LA) concentration and volume used in these studies was associated with a significant increase muscle weakness due to motor nerve block. The purpose of the present retrospective study of patients undergoing total knee arthroplasty (TKA) was to assess the relative analgesic efficacy and functional outcomes of the low concentration, low volume of LA used in peripheral nerve blocks for postoperative pain management.
Methods
Twenty-four months of de-identified patient data were extracted from an electronic medical record system. All patients received opioids with or without continuous femoral and sciatic nerve block infusions for postoperative analgesia. Pain (resting and with activity), cumulative opioid and local anesthetic (LA) use were primary endpoints, participation in physical therapy, muscle strength deficits and length of hospital stay were secondary endpoints.
Results
Postoperative pain and opioid use were significantly lower in patients with peripheral nerve blocks (n = 1,329) than those with opioids alone (n = 439). There was no detectable decrease in strength associated with nerve blocks, while a significantly greater proportion of patients with nerve blocks were able to participate in physical therapy (PT) on postoperative day 1 (96.4% vs. 57.1%). These differences were not due to the impact of the surgeon per se, but whether or not the surgeon used nerve blocks for pain management. There was a small but statistically significant decrease in the average length of hospital stay in patients with blocks.
Conclusion
This analysis supports the use of low concentration, low volume of LA based peripheral nerve blocks for post-operative pain management.
doi:10.1111/pme.12652
PMCID: PMC4674268  PMID: 25545781

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