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1.  Preclinical Pharmacology and Opioid Combinations 
Pain medicine (Malden, Mass.)  2012;13(s1):S4-S11.
Although effective alone, opioids are often used in combination with other drugs for relief of moderate to severe pain. Guidelines for acute perioperative pain recommend the use of multimodal therapy for pain management although combinations of opioids are not specifically recommended. Mu opioid drugs include morphine, heroin, fentanyl, methadone, and morphine 6β-glucuronide (M6G). Their mechanism of action is complex, resulting in subtle pharmacological differences among them and with unpredictable differences in their potency, effectiveness, and tolerability among patients. Highly selective mu opioids do not bind to a single receptor. Rather, they interact with a large number of mu receptor subtypes with different activation profiles for the various drugs. Thus, mu-receptor-based drugs are not all the same and it may be possible utilize these differences for enhanced pain control in a clinical setting. These differences among the drugs raise the question of whether combinations might result in better pain relief with fewer side effects. This concept already has been demonstrated between two mu opioids in preclinical studies and clinical trials other combinations are ongoing. This article reviews the current state of knowledge about mu opioid receptor pharmacology, summarizes preclinical evidence for synergy from opioid combinations, and highlights the complex nature of the mu opioid receptor pharmacology.
doi:10.1111/j.1526-4637.2012.01335.x
PMCID: PMC3307386  PMID: 22420604
analgesia; combinations; mu receptor; opioid; synergy; MOR-1; morphine
2.  Addressing Both Depression and Pain in Late-Life: The Methodology of the ADAPT Study 
Pain Medicine (Malden, Mass.)  2012;13(3):405-418.
Objective
To describe the methodology of the first NIH-funded clinical trial for seniors with comorbid depression and chronic low back pain.
Methods
Randomized controlled effectiveness trial using stepped care methodology. Participants are ≥ 60 years old. Phase 1 (6 weeks) is open treatment with venlafaxine xr 150 mg/day and supportive management (SM). Response is two weeks of PHQ-9 ≤ 5 and at least 30% improvement in the average numeric rating scale for pain. Non-responders progress to phase 2 (14 weeks) in which they are randomized to high-dose venlafaxine xr (up to 300 mg/day) with Problem Solving Therapy for Depression and Pain (PST-DP) or high-dose venlafaxine xr and continued SM. Primary outcomes are the univariate pain and depression response and both observed and self-report disability. Survival analytic techniques will be used, and the clinical effect size will be estimated with NNT. We hypothesize that self-efficacy for pain management will mediate response for subjects randomized to venlafaxine xr and PST-DP.
Results
Not applicable.
Conclusions
The results of this trial will inform the care of these complex patients and further understanding of comorbid pain and depression in late-life.
doi:10.1111/j.1526-4637.2011.01322.x
PMCID: PMC3309151  PMID: 22313547
clinical trial; geriatrics; depression; back pain; survival analysis
3.  A DESCRIPTIVE FEASIBILITY STUDY TO EVALUATE SCHEDULED ORAL ANALGESIC DOSING AT HOME FOR THE MANAGEMENT OF POSTOPERATIVE PAIN IN PRESCHOOL CHILDREN FOLLOWING TONSILLECTOMY 
Pain Medicine (Malden, Mass.)  2012;13(3):472-483.
Objectives
The purpose of this study, in a sample of preschool children (ages 3 to 5 years; N=47), was to evaluate the feasibility of scheduled analgesic dosing following outpatient tonsillectomy in order to optimize pain management.
Methods
Parents were instructed to give their child acetaminophen with hydrocodone (167mg/5ml) every 4 hours around-the-clock for the first 3 days following surgery. Parents recorded ratings of their child’s pain with/without swallowing using the Faces, Legs, Activity, Cry, and Consolability (FLACC) behavioral pain scale, pain relief ratings, and severity of analgesic side effects in a home diary. Audiotaped interviews were conducted with parents to document descriptions of their experiences in managing their child’s pain at home.
Results
Mean FLACC scores with/without swallowing were less than 2 at each measurement time and pain relief scores increased over time. Total analgesic dose decreased and the number of missed doses increased over the first 3 days after surgery. Moderate-to-severe daytime sedation, nausea, vomiting, and constipation were reported by parents.
Discussion
Study results suggest that acetaminophen with hydrocodone is effective in relieving preschool children’s pain following tonsillectomy, and that parental adherence to a scheduled analgesic regimen decreases over time. Time-contingent dosing was associated with moderate to severe side effects, and should be addressed in discharge teaching with parents. Findings provide insight into parents’ perspective of pain management at home following tonsillectomy and methods for relieving their child’s pain.
doi:10.1111/j.1526-4637.2011.01324.x
PMCID: PMC3309176  PMID: 22313591
tonsillectomy pain; pediatric pain; postoperative pain management; acetaminophen with hydrocodone
4.  Ethnicity, catastrophizing, and qualities of the pain experience 
Pain medicine (Malden, Mass.)  2010;12(2):314-321.
Objective
It is generally well established that catastrophizing exerts a potent influence on individuals' experience of pain and accompanying emotional distress. Further, preliminary evidence has shown that meaningful differences among various pain relevant outcomes (e.g., pain ratings, endogenous pain inhibitory processes) can be attributed to individuals' ethnic background. The mechanisms that might explain ethnic differences in pain outcomes are unclear, and it remains to be fully established whether the relation between ethnicity and pain response may be indirectly affected by pain catastrophizing.
Design
In the current study, we examined differences in pain responses by ethnicity among healthy, young adults (N = 62), and attempted to determine whether such an ethnicity-pain relation was mediated by catastrophizing using the standard Pain Catastrophizing Scale (PCS) and a modified version of the PCS reflecting situational catastrophizing during a cold pressor task.
Results
Results showed that pain responses varied by ethnicity, as did reported catastrophizing. Catastrophizing mediated the relation between ethnicity and affective and sensory pain responses.
Conclusions
To better explicate our findings, we described the context in which these findings occurred following a ‘who, what, where, when, and why’ approach. This approach provides an efficient description of how our findings align with previous research, while identifying future research that should clarify the theoretical underpinnings of catastrophizing and pain and also inform clinical intervention.
doi:10.1111/j.1526-4637.2010.01015.x
PMCID: PMC3575103  PMID: 21143756
Pain; Pain Quality; Catastrophizing; Sex; Ethnicity
5.  Subjective sleep quality and ethnicity are interactively related to standard and situation-specific measures of pain catastrophizing 
Pain medicine (Malden, Mass.)  2011;12(6):913-922.
Objective
Sleep quality and ethnicity are related to a host of general health outcomes including the experience of pain, yet it remains unclear whether poor sleep quality and ethnicity might interactively affect pain catastrophizing and laboratory-evoked acute pain reports. The current study examined the cross-sectional associations of subjective sleep quality, ethnicity, and their interaction with pain catastrophizing and pain reports.
Design
Healthy (N = 149), ethnically diverse (58% Caucasian American, 23% Asian American, 19% African American) young adults were subjected to a cold pressor task (CPT). Prior to CPT, participants completed the Pittsburgh Sleep Quality Index (PSQI) and a standard version of the Pain Catastrophizing Scale (PCS). Following CPT, participants completed a situation-specific version of the PCS.
Results
Adjusted analyses revealed a significant sleep quality by ethnicity interaction for standard catastrophizing reports. Particularly, African Americans with poor overall sleep quality reported the greatest level of catastrophizing on the standard PCS relative to their Caucasian and Asian American counterparts. Furthermore, African Americans with poorer sleep efficiency reported greater catastrophizing on the situation-specific PCS compared to Caucasian and Asian Americans. Catastrophizing was significantly correlated with pain reports.
Conclusions
These results suggest that African Americans with poorer sleep quality may be at greater risk for catastrophizing, a known contributor to more intense pain and increased pain-related emotional distress. Whether interventions that improve the sleep quality of ethnic minorities affect pain catastrophizing is in need of investigation.
doi:10.1111/j.1526-4637.2011.01138.x
PMCID: PMC3575106  PMID: 21627765
Ethnicity; sleep quality; pain catastrophizing; cold pressor; disparities
6.  Correlates of Perceived Pain-Related Restrictions among Women with Fibromyalgia 
Pain medicine (Malden, Mass.)  2010;11(11):1698-1706.
Objective
To identify correlates of perceived pain-related restrictions in a community sample of women with fibromyalgia.
Method
The fibromyalgia group was composed of white women with a self-reported, physician-given fibromyalgia diagnosis (N = 238) from the Biopsychosocial Religion and Health Study (BRHS). BRHS respondents had participated in the larger Adventist Health Study-2. To identify associations with pain-related restrictions, we used hierarchical linear regression. The outcome measure was subjects' pain-related restrictions (one SF-12 version 2 item). Predictors included age, education, body mass index (BMI), sleep apnea, and fibromyalgia treatment in the last year, as well as standardized measures for trauma, major life stress, depression, and hostility. To better interpret the findings, pain-related restrictions also were predicted in women with osteoarthritis and no fibromyalgia.
Results
Women with fibromyalgia reporting the more severe pain-related restrictions were those who had experienced trauma accompanied by physical pain, were older, less educated, more depressed, more hostile, had high BMI scores, and had been treated for fibromyalgia in the last 12 months (adjusted R2 = 0.308). Predictors in women with osteoarthritis were age, BMI, treatment in the last 12 months, experience of a major life stressor, and greater depression symptom severity (adjusted R2 = 0.192).
Conclusions
In both groups, age, BMI, treatment in the last 12 months, and depression predicted pain-related restrictions. Experience of a traumatic event with physical pain was the strongest predictor in the fibromyalgia group. These findings may be useful in constructing novel treatments and prevention strategies for pain-related morbidity in fibromyalgia patients.
doi:10.1111/j.1526-4637.2010.00988.x
PMCID: PMC3539411  PMID: 21044260
Fibromyalgia; Osteoarthritis; Pain; Central Nervous System; Trauma; Stress
7.  Experimental pain ratings and reactivity of cortisol and soluble tumor necrosis factor-α receptor II following a trial of hypnosis: Results of a randomized controlled pilot study 
Pain Medicine (Malden, Mass.)  2012;13(1):29-44.
Objective
Current evidence supports the efficacy of hypnosis for reducing the pain associated with experimental stimulation and various acute and chronic conditions; however, the mechanisms explaining how hypnosis exerts its effects remain less clear. The hypothalamic-pituitary-adrenal (HPA) axis and pro-inflammatory cytokines represent potential targets for investigation given their purported roles in the perpetuation of painful conditions; yet, no clinical trials have thus far examined the influence of hypnosis on these mechanisms.
Design
Healthy participants, highly susceptible to the effects of hypnosis, were randomized to either a hypnosis intervention or a no-intervention control. Using a cold pressor task, assessments of pain intensity and pain unpleasantness were collected prior to the intervention (Pre) and following the intervention (Post) along with pain-provoked changes in salivary cortisol and the soluble receptor of tumor necrosis factor-α (sTNFαRII).
Results
Compared to the no-intervention control, data analyses revealed that hypnosis significantly reduced pain intensity and pain unpleasantness. Hypnosis was not significantly associated with suppression of cortisol or sTNFαRII reactivity to acute pain from Pre to Post; however, the effect sizes for these associations were medium-sized.
Conclusions
Overall, the findings from this randomized controlled pilot study support the importance of a future large-scale study on the effects of hypnosis for modulating pain-related changes of the HPA axis and pro-inflammatory cytokines.
doi:10.1111/j.1526-4637.2011.01293.x
PMCID: PMC3257832  PMID: 22233394
Hypnosis; Hypnotic analgesia; Pain; Cortisol; Tumor necrosis factor-α; HPA axis; Inflammation
8.  Analgesic Use for Knee and Hip Osteoarthritis in Community-Dwelling Elders 
Pain medicine (Malden, Mass.)  2011;12(11):1628-1636.
Objective
To examine the prevalence and correlates of non-opioid and opioid analgesic use and descriptively evaluate potential undertreatment in a sample of community-dwelling elders with symptomatic knee and/or hip osteoarthritis (OA).
Design
Cross-sectional
Setting
Health, Aging and Body Composition Study
Patients
652 participants attending the year 6 visit (2002-03) with symptomatic knee and/or hip OA.
Outcome Measures
Analgesic use was defined as taking ≥ 1 non-opioid and/or ≥ 1 opioid receptor agonist. Non-opioid and opioid doses were standardized across all agents by dividing the daily dose used by the minimum effective analgesic daily dose. Inadequate pain control was defined as severe/extreme OA pain in the past 30 days from a modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).
Results
Just over half (51.4%) reported taking at least one non-opioid analgesic and approximately 10% were taking an opioid, most (88.5%) of whom also took a non-opioid. One in five participants (19.3%) had inadequate pain control, 39% of whom were using < 1 standardized daily dose of either a non-opioid or opioid analgesic. In adjusted analyses, severe/extreme OA pain was significantly associated with both non-opioid (adjusted odds ratio [AOR]=2.44; 95% confidence interval [95% CI]=1.49-3.99) and opioid (AOR=2.64; 95% CI, 1.26-5.53) use.
Conclusions
Although older adults with severe/extreme knee and/or hip OA pain are more likely to take analgesics than those with less severe pain, a sizable proportion take less than therapeutic doses and thus may be undertreated. Further research is needed to examine barriers to optimal analgesic use.
doi:10.1111/j.1526-4637.2011.01249.x
PMCID: PMC3221937  PMID: 21992521
Aged; Analgesic; Osteoarthritis
9.  Improving the Pharmacologic Management of Pain in Older Adults: Identifying the Research Gaps and Methods to Address Them 
Pain medicine (Malden, Mass.)  2011;12(9):1336-1357.
Objective
There has been a growing recognition of the need for better pharmacologic management of chronic pain among older adults. To address this need, the National Institutes of Health Pain Consortium sponsored an “Expert Panel Discussion on the Pharmacological Management of Chronic Pain in Older Adults” conference in September, 2010, to identify research gaps and strategies to address them. Specific emphasis was placed on ascertaining gaps regarding use of opioid and non-steroidal anti-inflammatory medications because of continued uncertainties regarding their risks and benefits.
Design
Eighteen panel members provided oral presentations; each was followed by a multidisciplinary panel discussion. Meeting transcripts and panelists’ slide presentations were reviewed to identify the gaps, and the types of studies and research methods panelists suggested could best address them.
Results
Fifteen gaps were identified in the areas of treatment(e.g., uncertainty regarding the long-term safety and efficacy of commonly prescribed analgesics), epidemiology (e.g., lack of knowledge regarding the course of common pain syndromes), and implementation(e.g., limited understanding of optimal strategies to translate evidence-based pain treatments into practice). Analyses of data from electronic health care databases, observational cohort studies, and ongoing cohort studies (augmented with pain and other relevant outcomes measures) were felt to be practical methods for building an age-appropriate evidence base to improve the pharmacologic management of pain in later life.
Conclusions
Addressing the gaps presented in the current report was judged by the panel to have substantial potential to improve the health and well being of older adults with chronic pain.
doi:10.1111/j.1526-4637.2011.01211.x
PMCID: PMC3173592  PMID: 21834914
Analgesic use; chronic non-cancer pain; older adults
10.  Safety and efficacy of vagus nerve stimulation in Fibromyalgia: A Phase I/II proof of concept trial 
Pain medicine (Malden, Mass.)  2011;12(9):1406-1413.
Objective
We performed an open label Phase I/II trial to evaluate the safety and tolerability of vagus nerve stimulation (VNS) in patients with treatment-resistant fibromyalgia (FM) as well as to determine preliminary measures of efficacy in these patients.
Methods
Of 14 patients implanted with the VNS stimulator, 12 completed the initial 3 month study of VNS; 11 returned for follow-up visits 5, 8 and 11 months after start of stimulation. Therapeutic efficacy was assessed with a composite measure requiring improvement in pain, overall wellness, and physical function. Loss of both pain and tenderness criteria for the diagnosis of FM was added as a secondary outcome measure because of results found at the end of 3 months of stimulation.
Results
Side effects were similar to those reported in patients treated with VNS for epilepsy or depression and, in addition, dry mouth and fatigue were reported. Two patients did not tolerate stimulation. At 3 months, five participants had attained efficacy criteria; of these, two no longer met widespread pain or tenderness criteria for the diagnosis of FM. The therapeutic effect seemed to increase over time in that additional participants attained both criteria at 11 months.
Conclusions
Side effects and tolerability were similar to those found in disorders currently treated with VNS. Preliminary outcome measures suggested that VNS may be a useful adjunct treatment for FM patients resistant to conventional therapeutic management but further research is required to better understand its actual role in the treatment of FM.
doi:10.1111/j.1526-4637.2011.01203.x
PMCID: PMC3173600  PMID: 21812908
11.  Self-Management Strategies to Reduce Pain and Improve Function among Older Adults in Community Settings: A Review of the Evidence 
Pain medicine (Malden, Mass.)  2008;9(4):409-424.
Context
Self-management strategies for pain hold substantial promise as a means of reducing pain and improving function among older adults with chronic pain, but their use in this age group has not been well defined.
Objective
To review the evidence regarding self-management interventions for pain due to musculoskeletal disorders among older adults.
Design
We searched the Medline and Cumulative Index to Nursing and Allied Health Literature databases to identify relevant articles for review and analyzed English-language articles that presented outcome data on pain, function, and/or other relevant endpoints and evaluated programs/strategies that could be feasibly implemented in the community. Abstracted information included study sample characteristics, estimates of treatment effect, and other relevant outcomes when present.
Results
Retained articles (N = 27) included those that evaluated programs sponsored by the Arthritis Foundation and other programs/strategies including yoga, massage therapy, Tai Chi, and music therapy. Positive outcomes were found in 96% of the studies. Proportionate change in pain scores ranged from an increase of 18% to a reduction of 85% (median = 23% reduction), whereas change in disability scores ranged from an increase of 2% to a reduction of 70% (median = 19% reduction). Generalizability issues identified included limited enrollment of ethnic minority elders, as well as non-ethnic elders aged 80 and above.
Conclusions
Our results suggest that a broad range of self-management programs may provide benefits for older adults with chronic pain. Research is needed to establish the efficacy of the programs in diverse age and ethnic groups of older adults and identify strategies that maximize program reach, retention, and methods to ensure continued use of the strategies over time.
doi:10.1111/j.1526-4637.2008.00428.x
PMCID: PMC3407960  PMID: 18346056
Chronic Non-Malignant Pain; Older Adults; Community Setting; Self-Management Programs; Arthritis
12.  Painful Medical Conditions and Alcohol Use: A Prospective Study Among Older Adults 
Pain medicine (Malden, Mass.)  2011;12(7):1049-1059.
Objective
To determine associations between older adults’ baseline painful medical conditions and their 10-year drinking behavior, and whether personal and life context characteristics moderate these associations.
Method
At baseline, then 1, 4, and 10 years later, late-middle-aged community residents (M=61 years; n=1,291) were surveyed regarding their painful medical conditions, use of alcohol, and personal and life context characteristics. Latent growth modeling was used to determine concurrent and prospective relationships between painful medical conditions and 10-year drinking behavior, and moderating effects of personal and life context characteristics on these relationships.
Results
At baseline, individuals reporting more numerous painful medical conditions consumed alcohol less frequently, but had more frequent drinking problems, than did individuals with fewer such conditions. Being female and having more interpersonal social resources strengthened the association between painful medical conditions and less ethanol consumed. For men more so than women, more numerous painful medical conditions were associated with more frequent drinking problems. Baseline painful medical conditions alone had no prospective effect on 10-year change in drinking behavior, but being older and having more interpersonal social resources made it more likely that baseline painful medical conditions would predict decline over time in frequency of alcohol consumption and drinking problems.
Conclusions
Late-middle-aged individuals who have more numerous painful medical conditions reduce alcohol consumption but nonetheless remain at risk for more frequent drinking problems. Gender, age, and interpersonal social resources moderate the influence of painful medical conditions on late-life alcohol use. These results imply that older individuals with pain are at little immediate or long-term risk for increased alcohol consumption, but clinicians should remain alert to drinking problems among their older pain patients, especially men.
doi:10.1111/j.1526-4637.2011.01156.x
PMCID: PMC3146463  PMID: 21668742
pain; alcohol; drinking problems; older adults
13.  Individual Differences in Morphine and Butorphanol Analgesia: A Laboratory Pain Study 
Pain medicine (Malden, Mass.)  2011;12(7):1076-1085.
Objective
Responses to opioid analgesics are highly variable and the understanding of contributing factors is limited. This laboratory study was designed to examine the contributions of sex and race to inter-individual variability in responses to opioids.
Design
A randomized, double blind, mixed design was implemented in the evaluation of analgesic response to a μ-opioid agonist and mixed agonist-antagonist, using three well-validated experimental pain assays (thermal, pressure, and ischemic).
Subjects
Participants included a total of 142 healthy subjects (76M/66F), 119non-Hispanic whites and 23 African Americans.
Intervention
Three sessions of pain testing were completed prior to and following an intravenous administration of morphine (0.08 mg/kg), butorphanol (0.016 mg/kg), and placebo (saline) in counterbalanced order.
Outcome Measures
A change score was calculated from the difference between the pre-drug and post-drug values. Three separate change scores (morphine, saline, and butorphanol) were computed for each experimental pain variable. Mixed-model analyses of covariance were performed on analgesic change scores.
Results
Significant sex differences emerged for pre-drug pain measures with minimal differences for race. Sex differences in opioid analgesia were not demonstrated. However, significant race differences and race X drug interactions emerged for thermal, pressure, and ischemic pain measures. The pattern of results generally indicated that for pressure and ischemic pain, African American subjects showed greater analgesic responses to both medications compared to non-Hispanic whites. For thermal pain threshold, butorphanol but not morphine analgesia was greater for African Americans versus non-Hispanic whites.
Conclusions
Findings are among the first to demonstrate race differences in a laboratory study of opioid analgesia.
doi:10.1111/j.1526-4637.2011.01157.x
PMCID: PMC3155877  PMID: 21668741
Individual Differences; Experimental Pain; Opioid Analgesia; Race
14.  The Relationships Among Pain, Non-pain Symptoms, and Quality of Life Measures in Older Adults with Cancer Receiving Hospice Care 
Pain medicine (Malden, Mass.)  2011;12(6):880-889.
Gathering first hand or reported information about patients in the final stages of terminal cancer is difficult due to patient frailty, cognitive impairment, excessive fatigue and severity of illness, as well as gatekeeping by hospice providers and caregivers, and highly variable documentation practices.
Objective
We sought to further understand and elucidate end-of-life experiences in older cancer patients through the application of validated tools employed in the hospice setting. This paper summarizes data collected about pain, non-pain symptoms, and other aspects of quality of life (QOL) as reported by older hospice patients or their caregivers during the first two weeks of hospice care.
Design
Data was collected from an ongoing IRB approved research project with 94 older adults with cancer or their caregivers receiving service in a home setting from 14 Midwestern hospices. Participants completed one or two telephone interviews. Instruments used to gather information include the Brief Pain Inventory (BPI) and the Brief Hospice Inventory (BHI).
Results
Data analysis showed mean “worst pain” ratings significantly decreased from interview 1 to interview 2 and pain reports were significantly correlated with fatigue, anxiety, appetite, comfort, symptom control and overall QOL.
Conclusions
Our findings reinforce previously held views that older patients with cancer experience pain and non-pain symptoms. And both pain and non-pain symptoms can impact and confound the treatment of other symptoms and interfere with the patient's overall QOL. The results of this study support the assertion that hospice care can have a positive impact on pain severity and related suffering, as well as patient QOL as death approaches.
doi:10.1111/j.1526-4637.2011.01113.x
PMCID: PMC3117028  PMID: 21539700
older adult; cancer pain; pain assessment; pain management; quality of life; hospice
15.  Prescription Analgesic Use Among Young Adults: Adherence to Physician Instructions and Diversion 
Pain medicine (Malden, Mass.)  2011;12(6):898-903.
Objectives
To understand the extent to which medication adherence was related to diversion of prescription analgesics.
Design
Cross-sectional analyses of data from the College Life Study, a prospective study of young adults.
Setting
Participants were originally sampled as incoming first-time first-year college students from one large public university in the mid-Atlantic U.S.
Participants
192 young adults aged 21 to 26 who were prescribed an analgesic to treat acute pain in the past year.
Outcome Measure
Diversion of prescription analgesics. The study tested two competing hypotheses: 1) individuals who skip doses (Under-Users) are at greatest risk for diversion because they have leftover medication; and 2) individuals who over-use their prescriptions (Over-Users) are at greatest risk for diversion, perhaps because of a general propensity to engage in deviant behavior.
Results
58% followed physician’s instructions regarding their prescription analgesic medication;27% under-used and 16% over-used their prescribed medication. Twenty-seven percent of the total sample diverted their medication, with Over-Users being the most likely to divert (63%). Holding constant demographic characteristics and perceived harmfulness of nonmedical use, Over-Users were almost five times as likely as Adherent Users to divert analgesic medications (P<.05).
Conclusions
Further research is needed to better understand the relationship between adherence and diversion. If these findings are replicated, physicians who are involved in pain management for acute conditions among young adults should take steps to monitor adherence and reduce diversion of prescription analgesics.
doi:10.1111/j.1526-4637.2011.01107.x
PMCID: PMC3117100  PMID: 21539698
Diversion; Medication Adherence; Opioids; Prescription Analgesics; Young Adults
16.  Depression, Chronic Pain, and Suicide by Overdose: On the Edge 
Pain medicine (Malden, Mass.)  2011;12(Suppl 2):S43-S48.
Comorbid conditions that pose risks for suicide, especially depression, are prevalent in people living with chronic pain. The true numbers of failed attempts and successful suicides are unknown and may never be determined. Yet risk factors for suicidal ideation are so high in this population that it must be assumed that some proportion of those who die of drug overdoses might have intended to end their lives, not just temporarily relieve their pain. The purpose of this manuscript is to highlight to clinicians the important association between chronic pain and intentional self-harm. Contemporary understanding of the epidemiology of depression and suicide and the relationship to chronic pain will be reviewed. Recommendations for the use of validated and practical screening tools as part of a comprehensive clinical assessment and for approaches to suicide prevention and interventions as crucial components of chronic pain management are outlined.
doi:10.1111/j.1526-4637.2011.01131.x
PMCID: PMC3125689  PMID: 21668756
depression; chronic pain; opioid-related overdose; suicide
17.  Development and Preliminary Psychometric Testing of the Centrality of Pain Scale 
Pain medicine (Malden, Mass.)  2011;12(4):612-617.
Objective
To develop and begin to evaluate a new measure of the centrality of pain in patients’ lives.
Design
Cross-sectional survey and cognitive interviews.
Setting
Academic general internal medicine clinic.
Patients
65 adult internal medicine patients with chronic non-malignant pain (CNMP).
Outcome measures
We assessed content validity and clarity of the 10-item Centrality of Pain Scale (COPS) by soliciting feedback from chronic pain experts and by conducting cognitive interviews with patients with CNMP. We assessed internal consistency reliability using Cronbach’s alpha. We assessed construct validity by comparing the COPS with other measures of chronic pain morbidity including pain severity, depression, anxiety, physical and mental health function, PTSD, quality of life, and provider assessment.
Results
Healthcare providers felt the COPS had excellent face validity. Cognitive interviews revealed that patients’ understanding of the items matched the intended construct, the scale measured an important concept, and items were easy to understand. The COPS had excellent internal consistency (alpha=0.9). COPS was negatively associated with age (r=−0.29; p=0.02), but not with other demographic characteristics. Higher COPS scores were associated with poorer physical (r=−0.48; p<0.001) and mental (r=−0.39 ; p=0.002 ) health function, quality of life (r=−0.36; P=0.004) and provider assessment of stability (r=−0.38; p=0.004) as well as with greater pain grade (r=0.55; p<0.001) and depression (r=0.63; p<0.001). In multivariate analyses, age, physical and mental health function, and depression were independently associated with COPS.
Conclusions
The COPS has excellent internal consistency and construct validity. Additional studies are needed to further validate the scale.
doi:10.1111/j.1526-4637.2011.01072.x
PMCID: PMC3078964  PMID: 21392248
Chronic pain; quality of life; health function
18.  Reliability of a Preliminary Three-Dimensional Pain Mapping Program 
Pain medicine (Malden, Mass.)  2011;12(3):344-351.
OBJECTIVE
The objective of this preliminary investigation was to evaluate the test-retest reliability of a new pain assessment method referred to as Three-Dimensional Pain Mapping.
METHODS
In Study 1 one hundred and one chronic noncancer pain patients from four sites reported their pain using the method on two occasions (separated by approximately 10 days). The patients marked intensity, surface location, and depth of pain on a three-dimensional computer display of a male or female body. The model body could be rotated in order to mark multiple pain locations. In Study 2 twenty five patients from a single site were tested with a revised version of the mapping program used in Study 1. Each patient gave ratings on two occasions separated by approximately one week.
RESULTS
In Study 1 the intra-class correlations of the 3-D pain mapping measures were moderate to high for maximum pain intensity (0.73), vertical location of the point of maximum pain (0.94), and the number of pain marks (0.84). Correlations were low for the horizontal location of the point of maximum pain (0.56) and for the depth of pain (0.50). In Study 2, using the revised program, intra-class correlations were moderate for pain intensity (0.76), and high for the vertical (0.99) and horizontal (0.98) locations of the point of maximum pain, number of pain marks (0.89), and the depth of pain (0.84).
CONCLUSIONS
Three-dimensional pain mapping enables patients to report the location and intensity of their pain on all parts of the body, and such ratings are highly reliable. Future studies are needed to determine whether the clinical value of this method can improve the accuracy of pain diagnoses and the quality of pain management.
doi:10.1111/j.1526-4637.2010.01049.x
PMCID: PMC3079353  PMID: 21276186
pain assessment; pain mapping; computer methods
20.  Hysterectomy and predictors for opioid prescription in a chronic pain clinic sample 
Pain medicine (Malden, Mass.)  2011;12(2):196-203.
Objectives
To describe the prevalence of hysterectomy for women aged 18-45 seeking treatment at a chronic pain clinic, to describe patient characteristics (pain intensity, age, smoking status, hormone replacement status, and psychosocial factors) based on opioid and hysterectomy status, and to determine whether hysterectomy status predicted receipt of opioid prescription.
Design
Retrospective cross-sectional chart review.
Participants
Total 323 new female patients aged 18-45 who completed the Brief Pain Inventory-Short Form at initial evaluation at a chronic pain clinic during a 12-month period (July 2008- June 2009).
Measures
Data were collected from the Brief Pain Inventory and medical charts. Variables included opioid prescription, average pain intensity, pain type, age, hysterectomy status, smoking status, and pain-related dysfunction across domains measured by the Brief Pain Inventory. The association of opioid prescription with hysterectomy and other factors were determined by logistic regression.
Results
Prevalence of hysterectomy was 28.8%. Average pain intensity was not associated with either hysterectomy or opioid prescription status. However, hysterectomy and high levels of pain-related dysfunction were significantly and independently associated with opioid prescription after adjusting for age and pain intensity. More than 85% of women with hysterectomy and high pain-related dysfunction had opioid prescription.
Conclusions
Hysterectomy may confer risk for pain-related dysfunction and opioid prescription in women 45 and younger. More research is needed to understand (1) how patient characteristics influence prescribing patterns; and (2) the specific medical risks and consequences of chronic opioid therapy in this population.
doi:10.1111/j.1526-4637.2010.01038.x
PMCID: PMC3076049  PMID: 21223499
hysterectomy; chronic pain; opioids; pain-related dysfunction; hormone replacement
21.  A New Program in pain medicine for medical students: Integrating core curriculum knowledge with emotional and reflective development 
Pain medicine (Malden, Mass.)  2011;12(2):186-195.
Objective
Improvements in clinical pain care have not matched advances in scientific knowledge, and innovations in medical education are needed. Several streams of evidence indicate that pain education needs to address both the affective and cognitive dimensions of pain. Our aim was to design and deliver a new course in pain establishing foundation-level knowledge while comprehensively addressing the emotional development needs in this area.
Setting
118 first year medical students at Johns Hopkins School of Medicine.
Outcome measures
Performance was measured by multiple choice tests of pain knowledge, attendance, reflective pain portfolios and satisfaction measures.
Results
Domains of competence in pain knowledge included central and peripheral pain signaling, pharmacological management of pain with standard analgesic medications, neuromodulating agents and opioids; cancer pain, musculoskeletal pain, nociceptive, inflammatory, neuropathic, geriatric, and pediatric pain. Socio-emotional development (portfolio) work focused on increasing awareness of pain affect in self and others and enhancing the commitment to excellence in pain care. Reflections included observations on a brief pain experience (cold pressor test), the multi-dimensionality of pain, the role of empathy and compassion in medical care, the positive characteristics of pain-care role models, the complex feelings engendered by pain and addiction including frustration and disappointment, and aspirations and commitments in clinical medicine. The students completing feedback expressed high levels of interest in pain medicine as a result of the course.
Discussion
We conclude that a four-day pain course incorporating sessions with pain- specialists, pain medicine knowledge, and design-built elements to strengthen emotional skills is an effective educational approach.
doi:10.1111/j.1526-4637.2010.01050.x
PMCID: PMC3078763  PMID: 21276187
22.  Nociceptive Behavior following Hindpaw Burn Injury in Young Rats: Response to Systemic Morphine 
Pain medicine (Malden, Mass.)  2010;12(1):87-98.
Objective
Develop a burn injury model in young age rats.
Background
Management of pain after burn injury in pediatric patients is an unresolved clinical issue.
Methods
A burn injury model in young rats of 3–4 weeks old was developed by briefly immersing the dorsal part of the right hindpaw in a hot water bath (85°C) for 12 seconds under pentobarbital anesthesia.
Results
Burn injury, but not sham control, induced nociceptive behaviors (mechanical allodynia, thermal hyperalgesia) when examined on post-injury day 2, 4 and 7. In burn-injured rats, there was the upregulated expression of the NR1 subunit of the N-methyl-d- aspartate (NMDA) receptor, Akt1, Akt2, and protein kinase C γ (PKC γ), but downregulated expression of neuronal nitric oxide synthase (nNOS), inducible NOS (iNOS), and glycogen synthase kinase-3β (GSK-3β), within the spinal cord dorsal horn ipsilateral to burn injury. Moreover, intraperitoneal administration of a clinically available NMDA receptor antagonist dextromethorphan (30 mg/kg, once daily × 7 days beginning on day 7 after burn injury) attenuated mechanical allodynia and thermal hyperalgesia in burn-injured rats. Different from our previous finding in adult burn-injured rats, however, burn injury in young rats of this age did not spontaneously shift the morphine antinociceptive response curve to the right within the dose range used in the study when exposed to morphine for the first time, suggesting that the development of intrinsic tolerance to morphine antinociception may be different from adult rats following burn injury.
Conclusions
Our data suggest that this model may be used to explore the mechanisms of burn injury-induced nociception in young rats and to differentiate the sequelae from burn injury between adult and young rats under certain experimental conditions.
doi:10.1111/j.1526-4637.2010.01021.x
PMCID: PMC3059240  PMID: 21143761
Burn injury; Allodynia; Hyperalgesia; NOS; NMDAR; PKB/Akt; GSK-3β
23.  Pain catastrophizing and pain coping among methadone-maintained patients* 
Pain medicine (Malden, Mass.)  2010;12(1):79-86.
Objective
The aim of this study was to examine the association of pain catastrophizing and pain coping strategies with characteristic pain intensity (an average of worst, least, and typical pain intensity in the past week) and recent pain-related disability (an average of three measures of past week pain interference) in opioid dependent patients enrolled in a methadone maintenance treatment program (MMTP) who reported recent pain.
Design
Cross-sectional survey.
Patients
One hundred and eight MMTP patients who reported recent pain.
Measures
Participants completed measures of demographics, pain status (i.e. “chronic severe pain” [pain lasting at least 6 months with at least moderate pain intensity or significant pain interference in the past week] vs. “some pain” [pain in the past week not meeting the threshold of chronic severe pain]), characteristic pain intensity, recent pain-related disability, somatization, depression, catastrophizing, and pain coping strategies.
Results
Catastrophizing explained a significant proportion of the variance in characteristic pain intensity (14%) and recent pain-related disability (11%) after controlling for demographics, pain status, somatization, and depression. Mirroring the findings of studies of non-opioid dependent chronic pain patients, greater catastrophizing was associated with greater pain intensity and increases in recent pain-related disability. On average, the chronic severe pain group reported higher levels of catastrophizing than the some pain group.
Conclusion
Consistent with studies of patients with chronic pain who are not opioid dependent, our findings emphasize the importance of assessing and addressing catastrophizing in MMTP patients with pain.
doi:10.1111/j.1526-4637.2010.01002.x
PMCID: PMC3059771  PMID: 21087402
pain; opioid dependence; catastrophizing; coping; methadone
24.  Ischemic Hypersensitivity in Irritable Bowel Syndrome Patients 
Pain medicine (Malden, Mass.)  2010;11(11):1619-1627.
Objective
Mixed evidence exists regarding whether irritable bowel syndrome patients show increased somatic pain perception compared to controls. The current study used a deep, tonic somatic pain stimulus (ischemic pain) to evaluate somatic hypersensitivity in irritable bowel syndrome patients.
Methods
A total of 27 diarrhea-predominant and 15 constipation-predominant irritable bowel syndrome patients, and 29 controls participated in the study. The modified submaximal effort tourniquet procedure was performed to induce ischemic arm pain, and the time required to reach pain threshold and pain tolerance were recorded in seconds. All subjects completed the functional bowel disease severity index (FBDSI) scale as well as several psychosocial instruments. Group differences for threshold and tolerance were determined using a series of 1-way ANOVA tests followed by Tukey comparisons.
Results
Irritable bowel syndrome patients had a shorter time to ischemic threshold (F=34.606, p<0.001) and tolerance (F=38.656, p<0.001) compared to controls, however the groups did not differ on ratings of pain at the time of tolerance. Irritable bowel syndrome patients had a higher rating on the FBDSI scale compared to controls (p<0.001), and ischemic pain threshold was negatively correlated with the FBDSI score.
Conclusions
The results of this study suggest that a widespread alteration in central pain processing in irritable bowel syndrome patients may be present as they display hypersensitivity to ischemic arm pain, and ischemic pain threshold was associated with clinical symptoms. These findings could reflect a dysfunction in inhibitory pain systems in irritable bowel syndrome patients, as ischemic (deep) pain may be under tonic inhibitory control.
doi:10.1111/j.1526-4637.2010.00954.x
PMCID: PMC2972369  PMID: 21029350
Irritable bowel syndrome (IBS); ischemic pain; somatic pain; visceral hypersensitivity; somatic hypersensitivity; thermal hypersensitivity
25.  Computerized Progress Notes for Chronic Pain Patients Receiving Opioids; the Prescription Opioid Documentation System (PODS) 
Pain medicine (Malden, Mass.)  2010;11(11):1707-1717.
Objective
We herein provide a description of a health information technology tool using computer-assisted survey instruments as a methodology for documentation during long-term opioid therapy.
Design
We report our experience using the Prescription Opioid Documentation and Surveillance (PODS) System, a medical informatics tool that utilizes validated questionnaires to automate the assessment of opioid prescribing for chronic non-malignant pain.
Setting and Patients
Chronic pain patients answered questions that were presented on a computer terminal prior to each appointment in a Department of Veterans Affairs Pain Clinic.
Measures
Pain levels, activities of daily living, and screening for common psychological disorders were sought at each visit. Results were tabulated with some information gathered sequentially permitting evaluation of progress. Following a face-to-face interview, the clinician added additional comments to the medical record.
Results
By deploying a systematic series of questions that are recalled by the computer, PODS assures a comprehensive assessment.
Conclusions
The PODS fulfills medico-legal requirements for documentation and provides a systematic means of determining outcomes. This process facilitates the determination of the appropriate intervals between clinic visits by stratifying patients into high, moderate, and low risk.
doi:10.1111/j.1526-4637.2010.00977.x
PMCID: PMC3058744  PMID: 21044261
Opioids; Chronic pain; Outcome assessment

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