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1.  Can Biomarkers Differentiate Pain and No Pain Subgroups of Nonverbal Children with Cerebral Palsy? A Preliminary Investigation Based on Noninvasive Saliva Sampling 
Pain medicine (Malden, Mass.)  2014;16(2):249-256.
Assessing and treating pain in nonverbal children with developmental disabilities are a clinical challenge. Current assessment approaches rely on clinical impression and behavioral rating scales completed by proxy report. Given the growing health relevance of the salivary metabolome, we undertook a translational-oriented feasibility study using proton nuclear magnetic resonance (NMR) spectroscopy and neuropeptide/cytokine/hormone detection to compare a set of salivary biomarkers relevant to nociception.
Within-group observational design.
Tertiary pediatric rehabilitation hospital.
Ten nonverbal pediatric patients with cerebral palsy with and without pain.
Unstimulated (passively collected) saliva was collected using oral swabs followed by perchloric acid extraction and analyzed on a Bruker Avance 700 MHz NMR spectrometer. We also measured salivary levels of several cytokines, chemokines, hormones, and neuropeptides.
Partial least squares discriminant analysis showed separation of those children with/without pain for a number of different biomarkers. The majority of the salivary metabolite, neuropeptide, cytokine, and hormone levels were higher in children with pain vs no pain.
The ease of collection and noninvasive manner in which the samples were collected and analyzed support the possibility of the regular predictive use of this novel biomarker-monitoring method in clinical practice.
PMCID: PMC4332832  PMID: 25234580
Saliva; Metabolite; Pain; Developmental Disability; Nuclear Magnetic Resonance (NMR); Partial Least Squares Discriminant Analysis (PLS-DA)
2.  [No title available] 
PMCID: PMC4086300  PMID: 24308744
3.  Experience and knowledge of pain management in patients receiving outpatient cancer treatment: What do older adults really know about their cancer pain? 
Pain medicine (Malden, Mass.)  2013;15(1):52-60.
An individual’s ability to effectively manage their cancer pain is influenced by knowledge and perceptions regarding the pain experience. While significance of the physician’s knowledge of cancer pain management has been reported, much less is known how a patient’s knowledge may influence their ability to optimally manage their pain. The purpose of this study is to determine the influence identified health and social factors have on the knowledge and experience of cancer pain among older adults.
A prospective cross-sectional study of older Black and White patients presenting for outpatient cancer treatment.
Participants were surveyed on questions assessing pain severity, knowledge and experience of pain, self-efficacy for pain treatment, satisfaction with pain treatment, and additional social, health, and demographic characteristics. A series of hierarchical regression models were specified to examine predictors of cancer pain knowledge and experience.
Education, race, and trust were significant predictors of pain knowledge, whereas self-efficacy for pain, pain interference, and pain severity were indicators of the experience of cancer pain.
Knowledge and experience of (cancer) pain are contingent upon a myriad of social and clinical factors that are not exclusive, but rather coexisting determinants of health. Understanding older adults’ knowledge of pain may begin to diminish the imparities in the diagnosis and treatment of pain among this growing diverse population of older adults. It may similarly allow for programs to be tailored to fit the specific needs of the patient in the treatment and management of their cancer pain.
PMCID: PMC3947025  PMID: 24118873
older adults; pain knowledge and experience; pain severity; trust; self-efficacy; cancer pain
4.  Prescription coverage in indigent patients affects the use of long-acting opiates in the management of cancer pain 
Pain medicine (Malden, Mass.)  2013;15(1):42-51.
We tested the hypothesis that prescription coverage affects the prescribing of long-acting opiates to indigent inner city minority patients with cancer pain.
Materials and Methods
We conducted a chart review of 360 patients treated in the Oncology Practice at UMDNJ-University Hospital, who were prescribed opiate pain medications. Half the patients were Charity Care or Self Pay (CC/SP), without the benefit of prescription coverage, and half had Medicaid, with unlimited prescription coverage. We evaluated patients discharged from a hospitalization, who had three subsequent outpatient follow up visits. We compared demographics, pain intensity, the type and dose of opiates, adherence to prescribed pain regimen, unscheduled Emergency Department (ED) visits and unscheduled hospitalizations.
There was a significantly greater use of long-acting opiates in the Medicaid group than in the CC/SP group. The Medicaid group had significantly more African American patients and a greater rate of smoking and substance use and the CC/SP group disproportionately more Hispanic and Asian patients and less smoking and substance use. Hispanic and Asian patients were less likely to have long-acting opiates prescribed to them. Pain levels and adherence were equivalent in both groups and were not affected by any of these variables except stage of disease, which was equally distributed in the two groups.
Appropriate use of long-acting opiates for equivalent levels of cancer pain are influenced only by the availability of prescription coverage. The group without prescription coverage and receiving fewer long-acting opiates had disproportionately more Hispanic and Asian patients.
PMCID: PMC3947034  PMID: 24106748
5.  Can Quantitative Sensory Testing Move Us Closer to Mechanism-Based Pain Management? 
Pain medicine (Malden, Mass.)  2013;15(1):61-72.
This review summarizes the scientific literature relating to the use of quantitative sensory testing (QST) for mechanism-based pain management.
A literature search was undertaken using PubMed and search terms including quantitative sensory testing, pain, chronic pain, response to treatment, outcome measure.
Settings and Patients
Studies including QST in healthy individuals and those with painful disorders were reviewed.
Publications reported on QST methodological issues including associations among measures and reliability. We also included publications on the use of QST measures in case-control studies, their associations with biopsychosocial mechanisms, QST measures predicting clinical pain as well as predicting and reflecting treatment responses.
Although evidence suggests that QST may be useful in a mechanism-based classification of pain, there are gaps in our current understanding that need to be addressed including making QST more applicable in clinical settings. There is a need for developing shorter QST protocols that are clinically predictive of various pain subtypes and treatment responses without requiring expensive equipment. Future studies are needed examining the clinical predictive value of QST including sensitivity and specificity for pain classification or outcome prediction. These findings could enable third-party payers’ reimbursement, which would facilitate clinical implementation of QST.
With some developments, QST could become a cost-effective and clinically useful component of pain assessment and diagnosis, which can further our progress toward the goal of mechanism-based personalized pain management.
PMCID: PMC3947088  PMID: 24010588
Quantitative sensory testing; QST; pain; sensory function; phenotypes; pain management
6.  Allodynia and Descending Pain Modulation in Migraine: A Resting State Functional Connectivity Analysis 
Pain medicine (Malden, Mass.)  2013;15(1):154-165.
Most migraineurs develop cutaneous allodynia during migraines and many have cutaneous sensitization between attacks. Atypical pain modulation via the descending pain system may contribute to this sensitization and allodynia. The objective of this study was to test the hypothesis that compared to non-allodynic migraineurs, allodynic migraineurs have atypical periaqueductal gray (PAG) and nucleus cuneiformis (NCF) resting state functional connectivity (rs-fc) with other pain processing regions.
Ten minutes resting-state BOLD data were collected from 38 adult migraineurs and 20 controls. Seed-based analyses compared whole-brain rs-fc with PAG and with NCF in migraineurs with severe ictal allodynia (n=8) to migraineurs with no ictal allodynia (n=8). Correlations between the strength of functional connections that differed between severely allodynic and non-allodynic migraineurs with allodynia severity were determined for all migraineurs (n=38). PAG and NCF rs-fc in all migraineurs was compared to rs-fc in controls.
Migraineurs with severe allodynia had stronger PAG and NCF rs-fc to other brainstem, thalamic, insula and cerebellar regions that participate in discriminative pain processing, as well as to frontal and temporal regions implicated in higher-order pain modulation. Evidence that these rs-fc differences were specific for allodynia included: 1) strong correlations between some rs-fc strengths and allodynia severity among all migraineurs; 2) absence of overlap when comparing rs-fc differences in severely allodynic vs. non-allodynic migraineurs with those in all migraineurs vs. controls.
Atypical rs-fc of brainstem descending modulatory pain regions with other brainstem and higher-order pain modulating regions is associated with migraine-related allodynia.
PMCID: PMC4188437  PMID: 24165094
Migraine; Functional Connectivity; Functional Magnetic Resonance Imaging; Allodynia; Central Sensitization
7.  Sex Differences in the Medical Care of VA Patients with Chronic Non-Cancer Pain 
Pain medicine (Malden, Mass.)  2013;14(12):10.1111/pme.12177.
Despite a growing number of women seeking medical care in the VA system, little is known about the characteristics of their chronic pain or the pain care they receive. This study sought to determine if sex differences are present in the medical care veterans received for chronic pain.
Retrospective cohort study using VA administrative data.
17,583 veteran patients with moderate to severe chronic non-cancer pain treated in the Pacific Northwest during 2008.
Multivariate logistic regression assessed for sex differences in primary care utilization, prescription of chronic opioid therapy, visits to emergency departments for a pain-related diagnosis, and physical therapy referral.
Compared to male veterans, female veterans were more often diagnosed with two or more pain conditions and had more of the following pain-related diagnoses: fibromyalgia, low back pain, inflammatory bowel disease, migraine headache, neck or joint pain, and arthritis. After adjustment for demographic characteristics, pain diagnoses, mental health diagnoses, substance use disorders, and medical comorbidity, women had lower odds of being prescribed chronic opioid therapy (AOR 0.67, 95% CI 0.58–0.78), greater odds of visiting an emergency department for a pain-related complaint (AOR 1.40, 95% CI 1.18–1.65), and greater odds of receiving physical therapy (AOR 1.19, 95% CI 1.05–1.33). Primary care utilization was not significantly different between sexes.
Sex differences are present in the care female veterans receive for chronic pain. Further research is necessary to understand the etiology of the observed differences and their associations with clinical outcomes.
PMCID: PMC3866355  PMID: 23802846
Chronic pain; veteran women; sex differences; chronic opioid therapy
8.  Pain is Independently Associated with Impaired Physical Function in HIV-infected Patients 
Pain medicine (Malden, Mass.)  2013;14(12):10.1111/pme.12255.
HIV-infected patients in the current treatment era can achieve normal life expectancies, but experience a high degree of medical and psychiatric comorbidity. Impaired physical function and pain, often in the context of mood disorders and substance abuse, are common in HIV-infected patients. The objective of this study was to investigate the relationship of pain, a modifiable condition, to functional impairment in HIV-infected patients, independent of mood disorders and substance abuse.
Participants in a prospective cohort of HIV-infected patients at the University of Alabama at Birmingham were included. Patient-reported outcome measures were used to cross-sectionally assess pain and physical function (EuroQOL), mood disorders (PHQ), and substance abuse (ASSIST). Univariate and multivariable models were built with pain as the principal independent variable of interest and 3 domains of physical function (mobility, self-care, and usual activities) as outcomes. Covariates included mood, substance abuse, age, race, sex, insurance status, HIV transmission risk factor, and CD4+ T-cell count.
Among 1903 participants, 693 (37%) reported pain; 509 (27%) had a mood disorder; and 157 (8.4%) reported current substance abuse. In multivariable models, pain was independently associated with increased odds of impairment in all three domains of physical function investigated – mobility (aOR 10.5, 95% CI 7.6–14.6), self-care (aOR 4.1, 95% CI 2.2–7.4), and usual activities (aOR 5.4, 95% CI 4.0–7.4).
Pain was associated with substantially increased odds of impairment in physical function. Pain should be an important consideration in HIV primary care. Interventions to address pain and impaired physical function should be investigated.
PMCID: PMC3886835  PMID: 24119077
HIV; pain; physical function; mental health; substance abuse
10.  Psychosocial and Demographic Correlates of Employment versus Disability Status in a National Community Sample of Adults with Chronic Pain: Toward a Psychology of Pain Presenteeism 
Pain medicine (Malden, Mass.)  2013;14(11):10.1111/pme.12234.
Although chronic pain is a source of work-related disability, relatively little research has addressed the psychological factors that differentiate individuals in chronic pain who leave the workforce from those who remain on the job despite their pain.
The present study examined a small set of attitudinal and coping-related factors as potential correlates of pain-related disability versus continued part- or full time employment over and above the role of well-known risk factors.
A large sample of adult men and women with chronic pain drawn from across the United States (N= 1293) by means of random digit dialing was subdivided into two groups: working (N = 859) and on disability (N = 434). Both groups were interviewed (by telephone) to complete a set of instruments (called the Profile of Chronic Pain: Extended Assessment [PCP: EA] Battery) measuring pain attitudes and coping methods.
Logistic regression analysis revealed, as expected, that continued employment status was inversely related to pain severity and work status was positively related to higher education and being Hispanic. After controlling for severity and demographic factors, belief in a medical cure and catastrophizing tendencies were significant inverse predictors and task persistence was a positive predictor of continued employment.
Results revealed both demographic and attitudinal predictors of continued employment, and highlight the value of harnessing insights from the psychology of work engagement to better understand the processes underlying pain presenteeism. Interventions designed to keep persons with pain in the active work force should build upon and extend the present findings.
PMCID: PMC3833889  PMID: 24010682
Chronic pain and disability; pain presenteeism; coping; work motivation
11.  Patients as collaborators: Using focus groups and feedback sessions to develop an interactive, web-based self-management intervention for chronic pain 
Pain medicine (Malden, Mass.)  2013;14(11):10.1111/pme.12200.
To describe the development of an interactive, web-based self-management intervention for opioid-treated, chronic pain patients with aberrant drug-related behavior.
Fifty-three chronic pain patients participated in either focus groups (n=23) or individual feedback sessions (n= 30). Focus groups probed interest in and relevance of the planned content and structure of the program. Individual session participants reviewed draft program modules and provided feedback on acceptability, ease of use, usefulness. Focus group transcripts were thematically analyzed and summary statistics were performed on feedback data.
Focus group participants stressed the need for additional pain management strategies and emphasized themes consistent with planned program content related to: (1) ambivalence about opioids; (2) reciprocal relationships among cognition, mood, and pain; (3) importance of recognizing physical limitations; and (4) effectiveness of goal setting for increasing motivation and functioning. Participants also offered insights on: (5) the loss of identity due to chronic pain; and (6) the desire to connect with pain peers to share strategies for managing daily life. Feedback session data demonstrate that participants believed that a web-based tool would be potentially useful and acceptable, and that exposure to program sections significantly increased participants’ knowledge of key topics related to self-management of chronic pain.
Results suggest the potential value of self-management for chronic pain patients and the potential acceptability of web-based delivery of intervention content. Focus group and feedback methodologies highlight the usefulness of including potential program users in intervention development.
PMCID: PMC3834126  PMID: 23859438
self-management; chronic pain; cognitive behavior therapy; Internet
12.  Frequency, Characteristics, and Correlates of Pain in a Pilot Study of Colorectal Cancer Survivors 1–10 Years Post-Treatment 
Pain medicine (Malden, Mass.)  2013;14(11):1673-1680.
The long-term effects of disease and treatment in colorectal cancer (CRC) survivors are poorly understood. This study examined the prevalence and characteristics of pain in a sample of CRC survivors up to 10 years post-treatment.
One hundred cancer-free CRC survivors were randomly chosen from an institutional database and completed a telephone survey using the Brief Pain Inventory, Neuropathic Pain Questionnaire-Short Form, Quality of Life Cancer Survivor Summary, Brief Zung Self-Rating Depression Scale, Zung Self-Rating Anxiety Scale, and Fear of Recurrence Questionnaire.
Participants were primarily Caucasian (90%) married (69%) males (53.5%) with a mean age of 64.7 years. Chronic pain was reported in 23% of CRC survivors, with a mean moderate intensity rating (mean = 6.05, standard deviation = 2.66) on a 0–10 rating scale. Over one-third (39%) of those with pain attributed it to their cancer or treatment. Chi-square and t-test analyses showed that survivors with pain were more likely to be female, have lower income, be more depressed and more anxious, and show a higher endorsement of suicidal ideation than CRC survivors without chronic pain. On average, pain moderately interfered with daily activity.
Chronic pain is likely a burdensome problem for a small but not inconsequential minority of CRC survivors requiring a biopsychosocial treatment approach to improve recognition and treatment. Open dialogue between clinicians and survivors about physical and emotional symptoms in long-term follow-up is highly recommended.
PMCID: PMC3971863  PMID: 24010414
Colorectal Cancer; Survivor; Pain; Quality of Life; Pain Interference
13.  Experimental Pain Phenotype Profiles in a Racially and Ethnically Diverse Sample of Healthy Adults 
Pain medicine (Malden, Mass.)  2013;14(11):1708-1718.
To examine patterns of interindividual variability in experimental pain responses emerging from multiple experimental pain measures in a racially/ethnically diverse sample of healthy adults and to examine the association between the derived phenotype profiles with demographic, psychological, and health-related measures.
Two hundred and ninety-one participants underwent heat, cold, pressure, and ischemic pain assessments, and completed several psychological and health-related assessments. The experimental pain measures were subjected to a principal component analysis and factor scores were used to compute Pain Sensitivity Index scores. The scores were subsequently submitted to a cluster analysis to identify patterns of pain sensitivity across experimental pain modalities.
The sample was equally composed of non-Hispanic whites, African Americans, and Hispanic whites. Sensitivity scores were computed for heat pain, pressure pain, cold pain, ischemic pain, and temporal summation of heat pain. Five distinct clusters were characterized by high heat pain sensitivity, low ischemic pain sensitivity, low cold pain sensitivity, low pressure pain sensitivity, and high temporal summation. Cluster membership was significantly different by sex as well as somatic reactivity and catastrophizing, although cluster differences were most pronounced between the heat pain-sensitive individuals vs the cold pain-insensitive individuals.
Our findings highlight the importance of phenotyping individuals to account for interindividual differences in pain responses. Our findings also replicate previously reported pain phenotypes, which are not solely related to demographic, psychosocial, or health-related factors in our healthy participants. Future studies designed to elucidate the biological underpinnings of pain sensitivity profiles would be of substantial value.
PMCID: PMC3983947  PMID: 23889771
Experimental Pain; Pain Phenotypes; Cluster Analysis; Factor Analysis; Pain Profiles
14.  Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies 
Pain medicine (Malden, Mass.)  2013;14(7):1039-1047.
There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared to placebo.
This study was a phase II, randomized, double blind, placebo-controlled, four-period crossover multi-center study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary.
A total of 15 patients were enrolled from 8 study sites and 8 patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared to placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study drop-out.
Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed.
PMCID: PMC4207215  PMID: 23565581
15.  Denial of Prescription Opioids Among Young Adults with Histories of Opioid Misuse 
Pain medicine (Malden, Mass.)  2012;13(8):1040-1048.
An exploratory study was undertaken to examine how being denied prescription opioids to treat pain impacted the drug-using careers of young adults with a history of misuse of prescription drugs.
Ethno-epidemiological methodology utilizing a cross-sectional design, semi-structured interviews, and qualitative/quantitative data analysis.
Non-clinical participants were recruited from natural settings, such as streets, parks, beaches, and college campuses, in New York City and Los Angeles during 2008 and 2009.
One hundred fifty participants aged 16 to 25 who had misused a prescription opioid, tranquilizer, or stimulant in the past 90 days.
Outcome Measures
Analyses focused on denial of opioids and associated consequences, including self-medication with prescription opioids and heroin.
Thirty-four participants (22.7%) described being denied prescription opioids for the treatment of a painful condition. Current opioid misuse and current pain problems were higher in this group compared to those who had never been denied prescription opioids. Reasons for denial included being identified as a drug user by a physician, lack of health insurance, and having medication withheld by a parent or authority figure. Approximately half reported self-medicating pain with either illegally obtained prescription opioids or heroin. Self-medication often coincided with initiation of new risk behaviors and more intensive drug use.
Being denied prescription opioids was an important moment in the drug using careers of many study participants. Results suggest that effective pain management techniques are needed to prevent high-risk young adults with pain problems from engaging in escalated opioid misuse and risk behaviors.
PMCID: PMC4184802  PMID: 22882357
Prescription Opioid Misuse; Heroin; Young Adults
16.  Perceived Stereotyping and Seeking Care for Chronic Vulvar Pain 
Pain medicine (Malden, Mass.)  2013;14(10):1461-1467.
We examined stereotyping of chronic pain sufferers among women aged 18 – 40 years and determined whether perceived stereotyping affects seeking care for women with chronic vulvar pain.
Cross-sectional study using a community-based survey of vulvodynia asking if “Doctors think that people with chronic pain exaggerate their pain”, and if “People believe that vulvar pain is used as an excuse to avoid having sex”.
Setting and Participants
12,834 women aged 18 – 40 years in metropolitan Minneapolis/St. Paul, Minnesota. Paul, Minnesota.
Outcome Measures
Women were considered to have a history of chronic vulvar pain if they reported vulvar burning lasting more than 3 months or vulvar pain on contact.
4,987 (38.9%) women reported a chronic pain condition; 1,651 had chronic vulvar pain. Women experiencing chronic pain were more likely than those without to perceive stereotyping from both doctors and others; a dose-response with the number of pain conditions existed. Women with chronic vulvar pain were more likely to believe that people think vulvar pain is an excuse to avoid intercourse. Half of the women with chronic vulvar pain did not seek medical care for it; of these, 40.4% perceived stereotyping from doctors. However, it was women who actually sought care (45.1%) who were more likely to feel stigmatized by doctors (adj. relative risk=1.11, 95% CI: 1.01-1.23).
Perceived negative stereotyping among chronic pain sufferers is common, particularly negative perceptions about physicians. In fact, chronic vulvar pain sufferers who felt stigmatized were more likely to have sought care than those who didn't feel stigmatized.
PMCID: PMC4036065  PMID: 23742116
Vulvodynia; stigma; stereotype; chronic pain; seeking care
Pain medicine (Malden, Mass.)  2014;15(7):1179-1186.
Prescription drug monitoring programs (PDMP) are now active in most states to assist clinicians in identifying potential controlled drug misuse, diversion or excessive prescribing. Little is still known about the ways in which they are incorporated into workflow and clinical decision making, what barriers continue to exist, and how clinicians are sharing PDMP results with their patients.
Qualitative data were collected through online focus groups and telephone interviews
Clinicians from pain management, emergency and family medicine, psychiatry/behavioral health, rehabilitation medicine, internal medicine and dentistry.
35 clinicians from 9 states participated.
We conducted two online focus groups and seven telephone interviews. A multidisciplinary team then used a grounded theory approach coupled with an immersion-crystallization strategy for identifying key themes in the resulting transcripts.
Some participants, mainly from pain clinics, reported checking the PDMP with every patient, every time. Others checked only for new patients, for new opioid prescriptions, or for patients for whom they suspected abuse. Participants described varied approaches to sharing PDMP information with patients, including openly discussing potential addiction or safety concerns; avoiding discussion altogether; and approaching discussion confrontationally. Participants described patient anger or denial as a common response and noted the role of patient satisfaction surveys as an influence on prescribing.
Routines for accessing PDMP data and how clinicians respond to it vary widely. As PDMP use becomes more widespread, it will be important to understand what approaches are most effective for identifying and addressing unsafe medication use.
PMCID: PMC4180422  PMID: 24833113
prescription drug abuse; PDMP; Doctor-patient interaction
18.  Pain among Older Hispanics in the U.S. Is Acculturation associated with Pain? 
Pain medicine (Malden, Mass.)  2013;14(8):1134-1139.
Previous studies suggest that acculturation may influence the experience of pain.
Study design
We conducted a cross-sectional study to estimate the association between acculturation and the prevalence, intensity, and functional limitations of pain in older Hispanic adults in the U.S.
Participants were English-speaking (HE) and Spanish-speaking (HS) Hispanic and non-Hispanic White (NHW) individuals aged 50 years and older who were interviewed for the Health and Retirement Study during 1998–2008.
We measured (a) acculturation as defined by language used in interviews and (b) the presence, intensity and functional limitations of pain.
We applied logistic regression using generalized estimating equations, with NHW as the reference category.
Among18,593 participants (16,733 NHW, 824 HE, 1,036 HS), HS had the highest prevalence (OR = 1.3; 95% CI = 1.1–1.4) and intensity (OR = 1.6; 95% CI = 1.4–1.9) of pain, but these differences were not significant after adjusting for age, sex, years of education, immigration status (U.S vs. non-U.S born) and health status (number of health conditions). Even after adjustment, HS reported the lowest levels of functional limitation (OR = 0.7; 95% CI 0.6–0.9).
Pain prevalence and intensity were not related to acculturation after adjusting for sociodemographic factors, while functional limitation was significantly lower among HS even after adjusting for known risk factors. Future studies should explore the reasons for this difference.
PMCID: PMC3748254  PMID: 23718576
Pain; older Hispanics; acculturation; language
19.  Medical Comorbidity is Associated with Persistent Index Hip Pain after Primary THA 
Pain medicine (Malden, Mass.)  2013;14(8):10.1111/pme.12153.
To characterize whether medical comorbidity predicts persistent moderate-severe pain after total hip arthroplasty (THA)
We analyzed the prospectively collected data from the Mayo Clinic Total Joint Registry for patients who underwent primary or revision THA between 1993–2005. Using multivariable-adjusted logistic regression analyses, we examined whether certain medical comorbidities were associated with persistent moderate-severe hip pain 2- or 5-years after primary or revision THA. Odds ratios (OR), along with 95% confidence intervals (CI) and p-value are presented.
The primary THA cohort consisted of 5,707 THAs and 3,289 THAs at 2- and 5-years, and revision THA, 2,687 and 1,627 THAs, respectively. In multivariable-adjusted logistic regression models, in the primary THA cohort, renal disease was associated with lower odds of moderate-severe hip pain (OR, 0.6; 95% CI, 0.3, 1.0) at 2-years. None of the comorbidities were significantly associated at 5-years. In the revision THA cohort, heart disease was significantly associated with higher risk (OR, 1.7; 95% CI, 1.1, 2.6) at 2-years and connective tissue disease with lower risk (OR, 0.5; 95% CI, 0.3, 0.9) of moderate-severe hip pain at 5-years follow-up.
This study identified new correlates of moderate-severe hip pain after primary or revision THA, a much-feared outcome of hip arthroplasty. Patients with these comorbidities should be informed regarding the increased risk or moderate-severe index hip pain, so that they can have a fully informed consent and realistic expectations.
PMCID: PMC3814009  PMID: 23742141
Pain; Function; functional limitation; Total hip replacement; primary; arthroplasty; joint replacement; outcomes; Patient-Reported Outcomes
20.  Psychological Variables Potentially Implicated in Opioid-Related Mortality as Observed in Clinical Practice 
Pain medicine (Malden, Mass.)  2011;12(0 2):S36-S42.
Opioid-related deaths in the United States have become a public health problem, with accidental and unintended overdoses being especially troubling. Screening for psychological risk factors is an important first step in safeguarding against nonadherence practices and identifying patients who may be vulnerable to the risks associated with opioid therapy. Validated screening instruments can aid in this attempt as a complementary tool to clinicians’ assessments. A structured screening is imperative as part of an assessment, as clinician judgment is not the most reliable method of identifying nonadherence. As a complement to formal screening, we present for discussion and possible future study certain psychological variables observed during years of clinical practice that may be linked to medication nonadherence and accidental overdose. These variables include catastrophizing, fear, impulsivity, attention deficit disorders, existential distress, and certain personality disorders. In our experience, chronic pain patients with dual diagnoses may become “chemical copers” as a way of coping with their negative emotion. For these patients, times of stress could lead to accidental overdose. Behavioral, cognitive-behavioral (acceptance and commitment, dialectical behavior), existential (meaning-centered, dignity), and psychotropic therapies have been effective in treating these high-risk comorbidities, while managing expectations of pain relief appears key to preventing accidental overdose.
PMCID: PMC4112122  PMID: 21668755
Opioids; Aberrant Drug-Related Behavior; Accidental Overdose; Chronic Pain; Pain Management; Risk Assessment
21.  Individual Variation in Sleep Quality and Duration Is Related to Cerebral Mu Opioid Receptor Binding Potential during Tonic Laboratory Pain in Healthy Subjects 
Pain medicine (Malden, Mass.)  2013;14(12):1882-1892.
Although poor sleep is a consequence of pain, sleep disturbance reciprocally induces hyperalgesia and exacerbates clinical pain. Conceptual models of chronic pain implicate dysfunctional supraspinal pain processing mechanisms, mediated in part by endogenous opioid peptides. Our preliminary work indicates that sleep disruption impairs psychophysical measures of descending pain modulation, but few studies have investigated whether insufficient sleep may be associated with alterations in endogenous opioid systems. This preliminary, exploratory investigation sought to examine the relationship between sleep and functioning of the cerebral mu opioid system during the experience of pain in healthy participants.
Subjects and Design
Twelve healthy volunteers participated in a 90-minute positron emission tomography imaging scan using [11C]Carfentanil, a mu opioid receptors agonist. During the session, pain responses to a 10% topical capsaicin cream were continuously rated on a 0–100 scale. Participants also completed the Pittsburgh Sleep Quality Index (PSQI).
Poor sleep quality (PSQI) was positively and significantly associated with greater binding potential (BP) in regions within the frontal lobes. In addition, sleep duration was negatively associated with BP in these areas as well as the temporal lobe and anterior cingulate.
These findings suggest that poor sleep quality and short sleep duration are associated with endogenous opioid activity in these brain regions during the application of a noxious stimulus. Elucidating the role of the endogenous opioid system in mediating some of the associations between sleep and pain could significantly improve our understanding of the pathophysiology of chronic pain and might advance clinical practice by suggesting interventions that could buffer the adverse effects of poor sleep on pain.
PMCID: PMC4104524  PMID: 24102962
Sleep; Pain; Capsaicin; PET; Imaging; Binding Potential; [11 C]Carfentanil
22.  Treating Intractable Phantom Limb Pain with Ambulatory Continuous Peripheral Nerve Blocks: A Pilot Study 
Pain medicine (Malden, Mass.)  2013;14(6):935-942.
There is currently no reliable treatment for phantom limb pain (PLP). Chronic PLP and associated cortical abnormalities may be maintained from abnormal peripheral input, raising the possibility that a continuous peripheral nerve block (CPNB) of extended duration may permanently reorganize cortical pain mapping, thus providing lasting relief.
Three men with below-the-knee (2) or -elbow (1) amputations and intractable PLP received femoral/sciatic or infraclavicular perineural catheter(s), respectively. Subjects were randomized in a double-masked fashion to receive perineural ropivacaine (0.5%) or normal saline for over 6 days as outpatients using portable electronic infusion. Four months later, subjects returned for repeated perineural catheter insertion (“crossover”), and received an ambulatory infusion with the alternate solution. Subjects were followed for up to one year.
By chance, all 3 subjects received saline during their initial infusion and reported little change in their PLP. One subject did not receive crossover treatment; but, the remaining 2 subjects reported complete resolution of their PLP during and immediately following treatment with ropivacaine. One subject experienced no PLP recurrence through the 52-week follow-up period; and, the other reported mild PLP occurring once each week of just a small fraction of his original pain (pre-treatment: continuous PLP rated 10/10; post-treatment: no PLP at baseline with average of 1 PLP episode each week rated 2/10) for 12 weeks (lost to follow-up thereafter).
A prolonged ambulatory CPNB may be a reliable treatment for intractable PLP. The results of this pilot study suggest that a large, randomized clinical trial is warranted.
PMCID: PMC3696484  PMID: 23489466
23.  Use of Machine-learning Classifiers to Predict Requests for Preoperative Acute Pain Service Consultation 
Pain medicine (Malden, Mass.)  2012;13(10):1347-1357.
The purpose of this project was to determine whether machine-learning classifiers could predict which patients would require a preoperative acute pain service consultation.
Retrospective cohort.
University teaching hospital.
The records of 9,860 surgical patients posted between January 1 and June 30, 2010 were reviewed.
Outcome Measures
Request for acute pain service consultation. A cohort of machine-learning classifiers was compared according to its ability or inability to classify surgical cases as requiring a request for a preoperative acute pain service consultation. Classifiers were then optimized utilizing ensemble techniques. Computational efficiency was measured with the central processing unit processing times required for model training. Classifiers were tested using the full feature set, as well as the reduced feature set that was optimized using a merit-based dimensional reduction strategy.
Machine-learning classifiers correctly predicted preoperative requests for acute pain service consultations in 92.3% (95% confidence intervals [CI], 91.8–92.8) of all surgical cases. Bayesian methods yielded the highest area under the receiver operating curve (0.87, 95% CI 0.84–0.89) and lowest training times (0.0018 seconds, 95% CI, 0.0017–0.0019 for the NaiveBayesUpdateable algorithm). An ensemble of high-performing machine-learning classifiers did not yield a higher area under the receiver operating curve than its component classifiers. Dimensional reduction decreased the computational requirements for multiple classifiers, but did not adversely affect classification performance.
Using historical data, machine-learning classifiers can predict which surgical cases should prompt a preoperative request for an acute pain service consultation. Dimensional reduction improved computational efficiency and preserved predictive performance.
PMCID: PMC4012229  PMID: 22958457
machine learning; pain; surgery; anesthesia; acute pain service
24.  Brief, Self-Report Fibromyalgia Screener Evaluated in a Sample of Chronic Pain Patients 
Pain medicine (Malden, Mass.)  2013;14(5):730-735.
To validate a self-report fibromyalgia screener in a chronic pain population.
Adults with chronic pain were evaluated with a 6-item, self-report fibromyalgia screening tool, based on revised American College of Rheumatology (ACR) fibromyalgia diagnostic criteria, with fibromyalgia diagnosed when patients experienced chronic pain and scored ≥13 on the ACR Fibromyalgia Symptom severity scale. Patients were independently assigned clinical diagnoses by treating clinicians.
University-based, tertiary care pain clinic
337 mixed chronic pain patients
Agreement between the clinical diagnosis and screener diagnosis was good (P<0.001), with 76% sensitivity and 82% specificity.
A self-administered, brief fibromyalgia screening questionnaire can effectively identify chronic pain patients who will likely have clinical fibromyalgia.
PMCID: PMC3663923  PMID: 23578002
chronic pain; fibromyalgia; screening tool; self report
25.  Swim therapy reduces mechanical allodynia and thermal hyperalgesia induced by chronic constriction nerve injury in rats 
Pain medicine (Malden, Mass.)  2013;14(4):516-525.
Neuropathic pain is common and often difficult to treat because it generally does not respond well to the currently available pain medications or nerve blocks. Recent studies in both humans and animals have suggested that exercise may induce a transient analgesia and reduce acute pain in normal healthy individuals. We examined whether swim therapy could alleviate neuropathic pain in rats.
Rats were trained to swim over a two week period in warm water. After the rats were trained, neuropathic pain was induced by constricting the right sciatic nerve and regular swimming was resumed. The sensitivity of each hind paw was monitored using the Hargreaves test and von Frey test to evaluate the withdrawal response thresholds to heat and touch.
The paw ipsilateral to the nerve ligation expressed pain-like behaviors including thermal hyperalgesia and mechanical allodynia. Regular swim therapy sessions significantly reduced the mechanical allodynia and thermal hyperalgesia. Swim therapy had little effect on the withdrawal thresholds for the contralateral paw. In addition, swim therapy alone did not alter the thermal or mechanical thresholds of normal rats.
The results suggest that regular exercise, including swim therapy, may be an effective treatment for neuropathic pain caused by nerve injuries. This study, showing that swim therapy reduces neuropathic pain behavior in rats, provides a scientific rationale for clinicians to test the efficacy of exercise in the management of neuropathic pain. It may prove to be a safe and cost-effective therapy in a variety of neuropathic pain states.
PMCID: PMC3625453  PMID: 23438327
Exercise; Neuralgia; Pain Management; Rehabilitation Medicine

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