David H. Bradshaw

Evaluating obesity in fibromyalgia: neuroendocrine biomarkers, symptoms, and functions

The aim of this study was to investigate the associations between obesity and fibromyalgia syndrome (FMS). This study was conducted at the University of Utah Pain Management and Research Center, Salt Lake City, Utah. Thirty-eight FMS patients were included in this study. Neuroendocrine indices (catecholamines, cortisol, C-reactive protein [CRP], and interleukin-6), symptom measures (Fibromyalgia Impact Questionnaire), sleep indices (Actigraph), and physical functioning (treadmill testing) were measured. Body mass index (BMI) provided the primary indicator of obesity. Approximately 50% of the patients were obese and an additional 21% were overweight. Strong positive associations were found between BMI and levels of IL-6 (r = 0.52) and epinephrine (r = 0.54), and somewhat weaker associations with cortisol (r = 0.32) and CRP (r = 0.37). BMI was also related to maximal heart rate (r = 0.33) and inversely related to distance walked (r = −0.41). BMI was associated with disturbed sleep: total sleep time (r = −0.56) and sleep efficiency (r = −0.44). No associations between self-reported symptoms and BMI were found. This study provides preliminary evidence suggesting that obesity plays a role in FMS-related dysfunction.

Improving Individual Measurement of Postoperative Pain: The Pain Trajectory

UNLABELLED The purpose of this study was to demonstrate a method for increasing the precision and information yield of postoperative pain assessment. We recorded pain intensity ratings over 6 days after surgery in 502 elective surgery patients and examined individual pain trajectories. A linear fit of an individual patients scores defines a trajectory with two features: (1) the intercept or initial pain intensity; and (2) the slope, or rate of pain resolution. Three pain trajectory patterns emerged from examination of the pain trajectory slopes. Most patients (63% of the sample) demonstrated a negative slope trajectory characterized by a decline in pain intensity over days after surgery. Other patients (25% of the sample) demonstrated a flat trajectory with no meaningful change over 6 days from pain they reported initially. A third patient group (12% of the sample) had a positive slope trajectory in which pain scores increased over 6 days after surgery. Measures derived from individual pain trajectories yielded much lower standard errors of measurement and therefore had better measurement precision than did conventional pain assessment methods. Pain trajectory measures proved sufficiently precise to characterize pain patterns reliably in individual patients. PERSPECTIVE Progress in acute pain management requires effective pain assessment. The acute pain trajectory quantifies rate of pain resolution as well as pain intensity. It affords more precise measurement than conventional pain assessment and can identify abnormal postoperative pain resolution.

Pain and the defense response: structural equation modeling reveals a coordinated psychophysiological response to increasing painful stimulation

&NA; The defense response theory implies that individuals should respond to increasing levels of painful stimulation with correlated increases in affectively mediated psychophysiological responses. This paper employs structural equation modeling to infer the latent processes responsible for correlated growth in the pain report, evoked potential amplitudes, pupil dilation, and skin conductance of 92 normal volunteers who experienced 144 trials of three levels of increasingly painful electrical stimulation. The analysis assumed a two‐level model of latent growth as a function of stimulus level. The first level of analysis formulated a nonlinear growth model for each response measure, and allowed intercorrelations among the parameters of these models across individuals. The second level of analysis posited latent process factors to account for these intercorrelations. The best‐fitting parsimonious model suggests that two latent processes account for the correlations. One of these latent factors, the activation threshold, determines the initial threshold response, while the other, the response gradient, indicates the magnitude of the coherent increase in response with stimulus level. Collectively, these two second‐order factors define the defense response, a broad construct comprising both subjective pain evaluation and physiological mechanisms.

Sequential analyses of daily symptoms in women with fibromyalgia syndrome

UNLABELLED Fibromyalgia syndrome (FMS) is a chronic musculoskeletal pain disorder characterized by generalized pain, chronic fatigue, sleep disturbance, and a range of other symptoms having no definitive pathology. Consequently, patient evaluations rely on self-report. Ecological Momentary Assessment (EMA) allows frequent real-time collection of self-report measures, removing recall bias and increasing external validity. We studied 81 females with FMS aged 18 to 42 years. Participants carried EMA devices (Palm Pilot M100) programmed to request ratings to 8 FMS symptoms/conditions 3 times daily for 30 days. Completeness of response rates varied across participants and over time. Controlling for immediately previous fatigue (ie, fatigue rating from the immediately preceding rating), unit increases in immediately previous pain and immediately previous emotional distress predicted 9 and 7% increases, respectively, in current fatigue. Controlling for immediately previous emotional distress, a unit increase in immediately previous pain predicted 7% increase in current emotional distress. Controlled for immediately previous pain, a unit increase in immediately previous fatigue predicted a 7% increase in current pain, enhanced by prior diurnal effects; immediately previous emotional distress was not significant. Collectively these results suggest an asymmetry in which emotional stress and pain may increase fatigue, fatigue but not emotional distress may increase pain, and pain but not fatigue may increase emotional distress. Despite small effects and person-to-person variability, these findings suggest that longitudinal data collection by EMA may reveal sequential or causal explanatory patterns with important clinical implications. PERSPECTIVE Understanding how multiple symptoms covary in FMS is essential for optimal treatment planning. Our results show small but significant temporal relations among pain, fatigue, and emotional distress. Our results also provide support for the use of EMA as a viable data collection method that allows longitudinal, real-time assessment of multiple FMS symptoms.

Outcome Evaluation of the Veterans Affairs Salt Lake City Integrative Health Clinic for Chronic Pain and Stress-Related Depression, Anxiety, and Post-Traumatic Stress Disorder

OBJECTIVES The purpose of this longitudinal outcome research study was to determine the effectiveness of the Integrative Health Clinic and Program (IHCP) and to perform a subgroup analysis investigating patient benefit. The IHCP is an innovative clinical service within the Veterans Affairs Health Care System designed for nonpharmacologic biopsychosocial management of chronic nonmalignant pain and stress-related depression, anxiety, and symptoms of post-traumatic stress disorder (PTSD) utilizing complementary and alternative medicine and mind-body skills. METHODS A post-hoc quasi-experimental design was used and combined with subgroup analysis to determine who benefited the most from the program. Data were collected at intake and up to four follow-up visits over a 2-year time period. Hierarchical linear modeling was used for the statistical analysis. The outcome measures included: Health-Related Quality of Life (SF-36), the Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Subgroup comparisons included low anxiety (BAI < 19, n = 82), low depression (BDI < 19, n = 93), and absence of PTSD (n = 102) compared to veterans with high anxiety (BAI > or = 19, n = 77), high depression (BDI > 19, n = 67), and presence of PTSD (n = 63). RESULTS All of the comparison groups demonstrated an improvement in depression and anxiety scores, as well as in some SF-36 categories. The subgroups with the greatest improvement, seen at 6 months, were found in the high anxiety group (Cohens d = 0.52), the high-depression group (Cohens d = 0.46), and the PTSD group (Cohens d = 0.41). CONCLUSIONS The results suggest IHCP is an effective program, improving chronic pain and stress-related depression, anxiety, and health-related quality of life. Of particular interest was a significant improvement in anxiety in the PTSD group. The IHCP model offers innovative treatment options that are low risk, low cost, and acceptable to patients and providers.

Trends in funding for research on pain: a report on the National Institutes Of Health grant awards over the years 2003 to 2007.

UNLABELLED In recent years, the National Institutes of Health (NIH) has experienced unprecedented reductions in its customary annual budget increases. Consequently, researchers, health care policy planners and others have a pressing need for accurate information on NIH funding patterns. We created a unique and objective system for compiling, classifying, and analyzing data on NIH grant awards and funding for research on pain, nausea, and dyspnea using naïve observers, cross-validation by multiple raters, and face validation by experts. We present results of our method and analyses for the period from 2003 to 2007. Following a 12% increase from 2003 to 2004, funding for pain research fell by 9.4% per year on average over the next 3 years. The percent of the total NIH budget going to support pain research increased to 0.78% in 2004 but fell to 0.61% in 2007. A piecewise regression model confirmed the declining trend represented a significant fit to the data (R(2)=0.98, p=0.024). Separate breakdowns by Institutes showed similar patterns. Analyses of nausea and dyspnea research support revealed small but steady increases over the same period. Declining support for pain research disproportionate to decreases in the NIH budget signals a need for measures to promote funding for meritorious applications. PERSPECTIVE Results of 5 year trends in numbers of grants and funding for research in pain, nausea, and dyspnea by the NIH show overall declines for pain but slight increases for nausea and dyspnea. Declining support for pain research that exceeds the reductions in the total NIH budget signals a need for measures to increase pain research funding.

Investigating dose-dependent effects of placebo analgesia: A psychophysiological approach

Summary Experimental laboratory data demonstrate that robust and persistent placebo analgesia can occur in a dose‐dependent manner, mediated by levels of expectancy for pain relief. ABSTRACT Investigating dose‐dependent effects of placebo analgesia (PA) in laboratory subjects undergoing pain testing, we evaluated 2 hypotheses: (1) greater expectancy for relief produces greater PA, and (2) cued expectancy for relief triggered by a predictive cue leads to more enhanced analgesia than does passive expectancy (no predictive cue). We used conditioning procedures in which 84 subjects experienced reduced stimulation intensity following the application of purported analgesic creams to the 2 experimental fingers, while the control finger received the same levels of stimulation as in the baseline block. The dose of placebos was manipulated by creating 2 levels of expectations for relief. The form of expectation (cued vs uncued) was also manipulated by a predictive cue specifying the next finger to be stimulated. Subjective reports and psychophysiological responses served as critical indicators for evaluating impacts of the placebo manipulation on subsequent pain processing. The dose‐dependent PA was unambiguously demonstrated by the predicted ordering of the 3 fingers (ie, manipulated expectation levels) in terms of both response sensitivity and average response magnitude, in mixed‐effects analysis of 3 outcome indicators (evoked potential, skin conductance response, pain report). Greater expectation for relief led to both (1) greater reductions in the average dependent variable slope (response sensitivity) as a function of stimulus intensity, and (2) greater reductions in average response magnitude. Unexpectedly, uncued expectation led to a slightly larger PA than did cued expectation. The study provided clear evidence that PA can occur in a “dose”‐dependent manner, mediated by the levels of expectancy for pain relief.

Effects of music engagement on responses to painful stimulation.

Objectives:We propose a theoretical framework for the behavioral modulation of pain based on constructivism, positing that task engagement, such as listening for errors in a musical passage, can establish a construction of reality that effectively replaces pain as a competing construction. Graded engagement produces graded reductions in pain as indicated by reduced psychophysiological arousal and subjective pain report. Methods:Fifty-three healthy volunteers having normal hearing participated in 4 music listening conditions consisting of passive listening (no task) or performing an error detection task varying in signal complexity and task difficulty. During all conditions, participants received normally painful fingertip shocks varying in intensity while stimulus-evoked potentials (SEP), pupil dilation responses (PDR), and retrospective pain reports were obtained. Results:SEP and PDR increased with increasing stimulus intensity. Task performance decreased with increasing task difficulty. Mixed model analyses, adjusted for habituation/sensitization and repeated measures within person, revealed significant quadratic trends for SEP and pain report (Pchange<0.001) with large reductions from no task to easy task and smaller graded reductions corresponding to increasing task difficulty/complexity. PDR decreased linearly (Pchange<0.001) with graded task condition. We infer that these graded reductions in indicators of central and peripheral arousal and in reported pain correspond to graded increases in engagement in the music listening task. Discussion:Engaging activities may prevent pain by creating competing constructions of reality that draw on the same processing resources as pain. Better understanding of these processes will advance the development of more effective pain modulation through improved manipulation of engagement strategies.

Outcome Evaluation of the Veterans Affairs Salt Lake City Integrative Health Clinic for Chronic Nonmalignant Pain

ObjectivesThe purpose of this longitudinal outcome study was to investigate the effectiveness of the Integrative Health Clinic and Program, an innovative outpatient clinical service that provides nonpharmacologic, biopsychosocial interventions using research based mind-body skills and complementary and alternative therapies. The study assessed improvement in chronic nonmalignant pain and related depression, anxiety, and health-related quality of life. MethodsThe study was a retrospective post-hoc quasi-experimental design with a group analysis comparing chronic nonspinal-related pain (CNSP) (eg, joint pain, headache, and fibromyalgia) (n=53) to chronic spinal-related pain (CSP) (eg, back pain and neck pain) (n=88). Data were collected at intake and up to 4 follow-up visits. Hierarchical Linear Modeling was used for statistical analysis. Outcome measures included: Quality of Life (Short Form-36), the Beck Depression Inventory, and Beck Anxiety Inventory. ResultsThere were statistically significant differences within and between the CNSP and CSP groups across all follow-up visits. For the CNSP group, depression, anxiety, and bodily pain significantly improved with moderate-to-large effect sizes at 6 months (Cohens d=0.74, 0.53, and 0.66, respectively) and these benefits persisted across all follow-up visits. The CSP group showed an improvement trend in bodily pain (Cohens d=0.26). DiscussionSignificant study findings revealed that the greatest improvement after participation in Integrative Health Clinic and Program were seen in the CNSP group with benefits persisting to 24 months in mood and in some health-related quality of life subcategories.

Central noradrenergic mechanisms and the acute stress response during painful stimulation

Events that threaten tissue integrity including noxious stimulation activate central noradrenergic circuits, particularly locus coeruleus and its projections. Recent advances in theory hold that an adaptive, defensive shift in brain activity takes place in response to threat. In principle, this shift may accentuate the autonomic and central biomarkers of the perception of painful events and the experience of pain itself. We have examined the effects of an alpha-2 agonist on pupil dilation responses, skin conductance responses, near field somatosensory evoked potentials and pain reports in normal volunteers undergoing repeated trials of painful fingertip stimulation delivered at low, medium and high intensities. In a double-blinded study, 114 healthy male and female volunteers underwent repeated noxious stimulation under baseline, placebo and active drug conditions where the active drug was the alpha-2 agonist tizanidine 4 mg. In contrast to baseline and placebo conditions, tizanidine 4 mg significantly reduced the magnitudes of the mean pupil dilation response, the mean skin conductance response, the mean near field somatosensory evoked potential peak-to-peak amplitude and the mean pain intensity rating. Stimulus intensity significantly altered all three biomarkers and the pain report in a graded fashion. There were no sex differences. These findings support the hypotheses that painful events activate central noradrenergic circuits, and that these circuits play a role in the autonomic and central arousal associated with pain.