Sickle cell bone disease and response to intravenous bisphosphonates in children.

Children with sickle cell disease (SCD) have the potential for extensive and early-onset bone morbidity. This study reports on the diversity of bone morbidity seen in children with SCD followed at three tertiary centers. IV bisphosphonates were effective for bone pain analgesia and did not trigger sickle cell complications. INTRODUCTION: To evaluate bone morbidity and the response to intravenous (IV) bisphosphonate therapy in children with SCD. METHODS: We conducted a retrospective review of patient records from 2003 to 2019 at three Canadian pediatric tertiary care centers. Radiographs, magnetic resonance images, and computed tomography scans were reviewed for the presence of avascular necrosis (AVN), bone infarcts, and myositis. IV bisphosphonates were offered for bone pain management. Bone mineral density was assessed by dual-energy X-ray absorptiometry (DXA). RESULTS: Forty-six children (20 girls, 43%) had bone morbidity at a mean age of 11.8 years (SD 3.9) including AVN of the femoral (17/46, 37%) and humeral (8/46, 17%) heads, H-shaped vertebral body deformities due to endplate infarcts (35/46, 76%), and non-vertebral body skeletal infarcts (15/46, 32%). Five children (5/26, 19%) had myositis overlying areas of AVN or bone infarcts visualized on magnetic resonance imaging. Twenty-three children (8/23 girls) received IV bisphosphonate therapy. They all reported significant or complete resolution of bone pain. There were no reports of sickle cell hemolytic crises, pain crises, or stroke attributed to IV bisphosphonate therapy. CONCLUSION: Children with SCD have the potential for extensive and early-onset bone morbidity. In this series, IV bisphosphonates were effective for bone pain analgesia and did not trigger sickle cell complications.

Somatosensory function in old age.

Sensory decline is viewed as an inevitable consequence of the ageing process. However, reports of declines have not been a consistent finding across the sensory systems. Reports from psychophysical studies indicate that the most common declines with ageing are in vision and audition and, to a lesser degree, olfaction and gustation. Findings for the somatosensory system (mechanoreception, warming and cooling thermoreception and pain) are less conclusive. Factors that contribute to individual differences in sensory ratings beyond chronological ageing include stimulus factors including stimulus type and body location, response measures and instructions, systemic disease that may affect the peripheral or central nervous system and environmental factors that may affect the skin integrity.

Investigating dynamic pain sensitivity in the context of the fear-avoidance model.

BACKGROUND: Although nearly everyone at some point in their lives experiences back pain; the amount of interference with routine activity varies significantly. The fear-avoidance (FA) model of chronic pain explains how psychological variables, such as fear, act as mediating factors influencing the relationship between clinical pain intensity and the amount of interference with daily activities. What remains less clear is how other mediating factors fit within this model. The primary objective of this report was to examine the extent to which a dynamic measure of pain sensitivity provides additional information within the context of the FA model. METHOD: To address our primary objective, classic mediation and moderated mediation analyses were conducted on baseline clinical, psychological and quantitative sensory measures obtained on 67 subjects with back pain (mean age, 31.4 ± 12.1 years; 70% female). RESULTS: There was a moderately strong relationship (r = 0.52; p < 0.01) between clinical pain intensity and interference, explaining about 27% of the variance in the outcome. Mediation analyses confirmed fear partially mediated the total effect of clinical pain intensity on interference (Δß = 0.27; p < 0.01), and accounted for an additional 16% of the variance. In our FA model, pain sensitivity did not demonstrate additional indirect effects; however, it did moderate the strength of indirect effects of fear. CONCLUSION: This preliminary modelling suggests complex interactions exist between pain-related fear and pain sensitivity measures that further explain individual differences in behaviour.

Analgesic and anti-hyperalgesic effects of muscle injections with lidocaine or saline in patients with fibromyalgia syndrome.

BACKGROUND: Patients with musculoskeletal pain syndrome including fibromyalgia (FM) complain of chronic pain from deep tissues including muscles. Previous research suggests the relevance of impulse input from deep tissues for clinical FM pain. We hypothesized that blocking abnormal impulse input with intramuscular lidocaine would decrease primary and secondary hyperalgesia and FM patients' clinical pain. METHODS: We enrolled 62 female patients with FM into a double-blind controlled study of three groups who received 100 or 200 mg of lidocaine or saline injections into both trapezius and gluteal muscles. Study variables included pressure and heat hyperalgesia as well as clinical pain. In addition, placebo factors like patients' anxiety and expectation for pain relief were used as predictors of analgesia. RESULTS: Primary mechanical hyperalgesia at the shoulders and buttocks decreased significantly more after lidocaine than saline injections (p = 0.004). Similar results were obtained for secondary heat hyperalgesia at the arms (p = 0.04). After muscle injections, clinical FM pain significantly declined by 38% but was not statistically different between lidocaine and saline conditions. Placebo-related analgesic factors (e.g., patients' expectations of pain relief) accounted for 19.9% of the variance of clinical pain after the injections. Injection-related anxiety did not significantly contribute to patient analgesia. CONCLUSION: These results suggest that muscle injections can reliably reduce clinical FM pain, and that peripheral impulse input is required for the maintenance of mechanical and heat hyperalgesia of patients with FM. Whereas the effects of muscle injections on hyperalgesia were greater for lidocaine than saline, the effects on clinical pain were similar for both injectates.

Using virtual human technology to capture dentists' decision policies about pain.

Healthcare professionals use race, gender, and age cues when making pain management decisions. Use of these demographic cues, therefore, is an important topic in the study of healthcare disparities. This study used virtual human (VH) technology to investigate the effects of VH patients' demographic cues on dentists' pain management decisions. Eighty-nine dentists viewed patients with different demographic cues. Analyses revealed that dentists rated pain intensity higher and were more willing to prescribe opioids to female, African-American, and younger patients than to their demographic counterparts. Results also found significant 2-way interactions between race and age for both pain assessment and treatment decisions. The interaction results suggest that the race difference (Caucasian < African American) was more pronounced for younger than for older patients. This is the first study to examine demographic cue use in dentists' decision-making for pain. The study found that dentists used demographic cues when making pain management decisions. Currently, there are no guidelines for decision- making practices for gender-, race-, or age-related pain. Since dentists see thousands of patients during their careers, the use of demographic cues could affect a substantial portion of the population. The findings could improve future training programs for dentists and dental students.

Temporal summation of second pain: variability in responses to a fixed protocol.

BACKGROUND: Temporal summation of second pain (TSSP) is relevant for the study of central sensitization, and refers to increased pain evoked by repetitive stimuli at a constant intensity. While the literature reports on participants whose pain ratings increase with successive stimuli, response to a TSSP protocol can be variable. The aim of this study was to characterize the full range of responses to a TSSP protocol in pain-free adults. METHOD: Three hundred twelve adults received a train of brief, repetitive heat stimuli at a fixed temperature and rated the intensity of second pain after each pulse. TSSP response (Δ in pain ratings) was quantified using the most common methods in the literature, and response groups were formed: TSSP (Δ > 0), no change (Δ = 0), and temporal decrease in second pain (TDSP) (Δ < 0). A cluster analysis was performed on the Δ values to empirically derive response groups. RESULTS: Depending on how TSSP response was quantified, 61-72% of the sample demonstrated TSSP, 11-28% had no change in pain ratings and 0-20% demonstrated TDSP. The cluster analysis found that the majority (59%) of participants fell in the no change cluster, 29% clustered into the TSSP group and 12% in the TDSP cluster. CONCLUSIONS: Using a fixed thermal paradigm, pain-free adults exhibit substantial variability in response to a TSSP protocol not well characterized by group-mean slopes. Studies are needed to determine TSSP response patterns in clinical samples, identify predictors of response and determine the clinical implications of response variability.

Integrating genetic studies of nicotine addiction into public health practice: stakeholder views on challenges, barriers and opportunities.

OBJECTIVE: Will emerging genetic research strengthen tobacco control programs? In this empirical study, we interview stakeholders in tobacco control to illuminate debates about the role of genomics in public health. METHODS: The authors performed open-ended interviews with 86 stakeholders from 5 areas of tobacco control: basic scientists, clinicians, tobacco prevention specialists, health payers, and pharmaceutical industry employees. Interviews were qualitatively analyzed using standard techniques. RESULTS: The central tension is between the hope that an expanding genomic knowledge base will improve prevention and smoking cessation therapies and the fear that genetic research might siphon resources away from traditional and proven public health programs. While showing strong support for traditional public health approaches to tobacco control, stakeholders recognize weaknesses, specifically the difficulty of countering the powerful voice of the tobacco industry when mounting public campaigns and the problem of individuals who are resistant to treatment and continue smoking. CONCLUSIONS: In order for genetic research to be effectively translated into efforts to minimize the harm of smoking-related disease, the views of key stakeholders must be voiced and disagreements reconciled. Effective translation requires honest evaluation of both the strengths and limitations of genetic approaches.

Age differences in orofacial sensory thresholds.

Declines in sensory functioning with aging are evident for many of the senses. In the present study, thresholds were determined for somatosensory (warming and cooling temperature, pain, touch, and two-point discrimination) and taste stimuli in 178 healthy individuals aged 20-89 yrs. Somatosensory stimuli were applied to the upper lip (glabrous skin) and the chin (hairy skin). The sample was divided into two groups, based on a bimodal split "< 45 yrs" and "≥ 65 yrs". In all instances, there were elevations in thresholds for the older individuals. Further, males were less sensitive than females for cool at the chin site, for touch, and for sour taste. We conclude that there are elevations in sensory thresholds with age for multimodal somatosensory and gustatory senses.

Overall fibromyalgia pain is predicted by ratings of local pain and pain-related negative affect--possible role of peripheral tissues.

OBJECTIVES: Despite variable numbers and intensities of local pain areas, fibromyalgia (FM) patients can provide overall clinical pain ratings. We hypothesized that the overall clinical pain is largely determined by the pain intensity of local body areas. Thus, we assessed the role of local body pains as predictors of overall clinical pain in FM patients. METHODS: Ratings of overall clinical pain intensity and pain-related negative affect (PRNA) were obtained from 277 FM patients. In addition, the patients identified painful body areas by shading a body pain diagram and rated the intensity of each pain area using a mechanical visual analogue scale (VAS). Hierarchical regression analyses were used to examine predictors of overall clinical FM pain intensity including PRNA, number of local pain areas, and maximal/average intensity of local pain areas. RESULTS: The average overall clinical pain rating of all FM patients was 4.6 (S.D. 2.3) VAS. The PRNA accounted for 19%, number of painful body areas for 9% and maximal/average local pain for 27% of the variance of overall clinical FM pain (P-values < 0.001). The combination of all factors predicted 55% of the variance in overall clinical pain intensity of FM patients. CONCLUSION: Peripheral factors (maximal/average local pain and number of painful body areas) predicted most of the variance of overall clinical FM pain, suggesting that the input of pain by the peripheral tissues is clinically relevant. About 19% of the pain variance was predicted by PRNA. Thus, peripheral pain and negative affect appear to be particularly relevant for overall FM pain and may represent important targets for future therapies.

Sex differences in delayed onset muscle soreness.

AIM: There is agreement that females report greater pain in response to typical experimental pain stimuli than males. However, investigations of sex differences in the sensation of delayed onset muscle soreness (DOMS) have equivocal RESULTS: The objective of this investigation was to examine sex differences in the pain from DOMS with an adequate sample size, quantification of stimulus intensity, and 2 measures of pain. METHODS: Sixty-seven participants (52% females) completed a 2-session protocol. DOMS was induced using eccentric resistance exercises in the elbow flexors of the non-dominant arm. The intensity of the eccentric contractions was based upon concentric strength. Pain response was measured 48 hrs later. The dependent variables were pressure threshold, which was assessed using a dolorimeter, and pain intensity when the arm was moved through full active range of motion, which was assessed with a visual analog scale. RESULTS: The occurrence of DOMS was confirmed by a decrease in pressure threshold after the eccentric contractions and higher pain intensity in the arm that performed the eccentric contractions than the arm that did not. Females reported lower pain intensities (M=3.41, SD=2.13) compared to males (M=5.12, SD=2.05), but no significant sex difference was found in pressure threshold. CONCLUSION: In this investigation, females reported lower muscle pain intensity than males, but showed no sex difference in pressure threshold. These and previous findings suggest that the detection of a sex difference in muscle pain depends upon the methodology of inducing DOMS and measuring sensation.

The influence of endurance exercise on delayed onset muscle soreness.

BACKGROUND: Despite several review articles supporting the existence of exercise induced analgesia, it is unclear whether exercise reduces delayed onset muscle soreness (DOMS). The purpose of this investigation was to examine the influence of an acute bout of endurance exercise on delayed onset muscle pain. METHODS: DOMS was induced in the elbow flexors of the non-dominant arm using eccentric isotonic exercise with the intensity of the eccentric contractions based upon concentric strength. Forty-eight hours after the eccentric contractions participants were randomly assigned to a group that completed 20 min of endurance exercise at 80% of estimated maximum cardiorespiratory endurance (n=23) or a group that watched a 20 min emotionally neutral video (n=27). The dependent variables were pressure pain threshold, pain intensity during arm movement through active range of motion, a standardized pain rating that was determined from a magnitude matching procedure, and state anxiety. RESULTS: A significant decrease in pressure pain threshold and an increase in the standardized pain ratings after the DOMS procedure (p<0.05) indicated that muscle pain was successfully induced. These changes were components of significant quadratic trends for pressure threshold (p<0.05) and the standardized pain ratings (p<0.01). During the 2nd session a decrease in pain intensity approached significance (p=0.05) regardless of group assignment. However, no significant group by time interactions were detected for any of the pain measures or state anxiety. CONCLUSIONS: Cycle ergometer exercise was not found to alter delayed onset muscle pain.

MMPI-2 profiles of patients with intractable epilepsy.

MMPI-2 profiles of 93 presurgical intractable epilepsy patients were examined using Ward's method of cluster analysis. Three clusters were identified. The means of each cluster suggest that 45% of the sample had minimal psychological complaints, 30% presented with generalized clinical elevations, and 25% of the patients had profiles of intermediate elevations with a tendency to emphasize somatic complaints and/or depression. Gender, age of seizure onset, and seizure laterality were not found to be uniquely associated with the cluster profiles. Further examination of correlates of group membership is warranted to provide information for treatment planning.

Sex, gender, and blood pressure: contributions to experimental pain report.

OBJECTIVE: The current study investigated whether the relationship between sex and experimental pain report was explained by systolic blood pressure (SBP) at rest or during pain task, by gender-role socialization as assessed by the Bem Sex Role Inventory, or both. The influence of gender-role socialization on pain report is often inferred but rarely studied. METHODS: Fifty female and 54 male healthy, young adults completed the Bem Sex Role Inventory and then underwent a cold pressor task. Blood pressure was assessed before and during pain testing. RESULTS: Univariate analyses indicated significant sex-related differences in pain threshold and pain tolerance. Baseline SBP was positively related to pain tolerance but did not explain sex differences, in accord with previous research. The Bem Sex Role Inventory demonstrated a relationship with pain, but did not explain sex differences. CONCLUSIONS: We suggest that context-specific measures of gender are needed to assess gender-related pain behaviors in specific situations. Results from the current study support our contention that gender is part of sex as commonly measured. Also, blood pressure does not appear to fully account for sex-related differences in pain.

Facilitation of quadriceps activation following a concentrically controlled knee flexion movement: the influence of transition rate.

STUDY DESIGN: Single group repeated measures design. OBJECTIVE: To determine if the rate of transition between knee flexion and extension influences the subsequent concentric activation of the quadriceps and knee extension torque during reciprocal movements. BACKGROUND: Preloading a muscle by stretching, a prior isometric or eccentric muscle action, or a prior movement controlled concentrically by the antagonist muscle group increases the maximal torque-generating capability of the agonist. We hypothesized that the rate of transition from the prior movement may be the critical factor that influences the degree of muscle facilitation and torque potentiation. Rapid reversal of antagonistic movements has been postulated as a potential facilitatory mechanism. METHODS: Knee extension torque and electromyographic (EMG) amplitude (dependent variables) from 2 of the vasti muscles were recorded while subjects (N = 20; 12 men, 8 women, mean age, 28.5+/-2.68 years) maximally activated their quadriceps at 3 constant angular velocities, 100 degrees/s, 200 degrees/s, and 300 degrees/s, and 2 preload conditions, SLOW and RAPID (independent variables). In the SLOW transition condition, subjects actively flexed their knee to 110 degrees from an extended position, paused in this position for 3 seconds, and then extended to 0 degrees. In the RAPID transition condition, the same movement from knee flexion to extension was performed without a pause. RESULTS: Peak torque, the root-mean-square (RMS) average, peak (peak rectified and smoothed), and initial (100 milliseconds prior to torque onset) EMG amplitudes were all significantly greater during the RAPID transition condition. Peak torque decreased with increasing movement velocity. There were no interactions between the preload conditions and angular velocity on peak torque or the EMG amplitude variables. There was also no influence of velocity on the EMG amplitude variables. CONCLUSIONS: The effect of preloading the quadriceps by prior concentric activation of the hamstrings is dependent on the rate of transition between the flexion and extension movements and is due primarily to neural facilitation.

Factors predicting orofacial pain patient satisfaction with improvement.

AIMS: To determine psychosocial predictors of patients' ratings of satisfaction with improvement and subjective pain relief. This study also examined the underlying components of patient satisfaction with improvement, as assessed at follow-up. METHODS: The sample consisted of 107 chronic orofacial pain patients evaluated at a university-based orofacial pain clinic and referred for treatment with individualized treatment plans. Pain and psychosocial functioning were assessed with standard, reliable, validated self-report instruments administered at the initial evaluation. Follow-up data were collected via a telephone-administered structured interview 8 months after the initial evaluation. Regression methodology was used to determine prediction models for satisfaction with improvement and subjective pain relief. Patient ratings of the quality of the caregiver communication were used as a control variable in all analyses. RESULTS: Quality of caregiver communication predicted approximately 10 to 14% of the variance in outcomes in all models. Greater initial use of cognitive coping strategies and reduced depression predicted higher ratings of satisfaction with improvement and increased pain relief. When concurrent relationships among variables at the follow-up were examined, greater subjective pain relief since the evaluation, lower current pain, and higher ratings of overall mood were significant predictors of patient satisfaction with improvement. CONCLUSION: This study is one of the first to report that the use of certain cognitive coping strategies is associated with positive outcome for patients suffering from orofacial pain. These findings underscore the importance of individual differences on behavioral and psychosocial parameters in the prediction of patients' subjective evaluation of treatment outcome.

Gender role expectations of pain: relationship to sex differences in pain.

Empirical research supports the existence of sex differences in pain; yet these differences are poorly understood. Although biological mechanisms have been posited to explain variability, results of pain modeling manipulations suggest social learning may be a stronger influence on pain response. In this report we use the term sex to refer to the biological category of male or female. We use the term gender to refer to the socially acquired aspects of being male or female sometimes referred to as femininity and masculinity. This study investigated a new measure, the Gender Role Expectations of Pain questionnaire (GREP), which was designed to measure sex-related stereotypic attributions of pain sensitivity, endurance, and willingness to report pain. Subjects were 156 male and 235 female undergraduates at a southeastern university. Psychometric investigation of the questionnaire revealed a 5-factor solution that closely mirrored the theoretical construction of the items. Test-retest reliability was also shown for individual items on a separate sample of 28 subjects. Results supported hypotheses about gender role: both men and women rated men as less willing to report pain than women (F(1,389) = 336, P <.001); both men and women rated women more sensitive (F(1,389) = 9.5, P <.05) and less enduring of pain (F(1,389) = 65.7, P <.001) than men; and men rated their own endurance as higher than the typical man (F(1,389) = 65.7, P <.001). Sex accounted for 46% of the variance in willingness to report pain. Results suggest that the GREP distinguished between the socially learned reactions to pain for men and women. It is recommended that the influence of gender-related expectations for pain be assessed in all studies investigating human sex differences in pain.

Perceived spouse responsiveness to chronic pain: three empirical subgroups.

The spouse plays a fundamental role in day-to-day functioning and long-term well-being of the patient with chronic pain. Although spouses may respond differently to pain demonstrations, no study has examined patterns of perceived spouse responsiveness to chronic pain behavior. Yet perceived patterns of response to chronic pain may explain variability in pain behavior in the literature because studied samples may be drawn from any one subgroup. The purposes of this study were to run an exploratory cluster analysis to identify naturally occurring spouse response subgroups by using section 2 of the Multidimensional Pain Inventory and to examine pain-relevant variables between subgroups. It was hypothesized that subgroups would be identified and that they would differ on pain-relevant variables. Participants were 774 married pain patients from 2 University of Florida-affiliated pain clinics, 69% of whom experienced chronic low back pain. A hierarchical cluster analysis identified 3 subgroups that were labeled positively attentive, negatively attentive, and inattentive. A discriminant analysis yielded 2 significant discriminant functions that correctly classified 71.1% of subgroup membership. The support variable best differentiated between the positively and negatively attentive subgroups, whereas interference best distinguished between the negatively attentive and inattentive subgroups. Results suggest the profiles have conceptual and clinical validity, with the negatively and positively attentive subgroups exhibiting the poorest adjustment to pain. A controlled study is needed to determine the direction of causality.

Sex differences in negative emotional responses to chronic pain.

We proposed a sequential model of pain processing with pain intensity as stage 1, pain unpleasantness as stage 2, pain-related emotions (depression, anxiety, frustration, anger, fear) as stage 3, and overt behavioral expression of pain as stage 4. We tested hypotheses about relationships between sex and the first 3 stages of pain processing by conducting simultaneous regression analysis using LISREL-8 with data collected from 967 women and 680 men with chronic pain. We found the following results: (1) women reported higher pain-related frustration and fear; (2) frustration related most highly to pain intensity among women, as compared with anxiety and depression among men; (3) depression and frustration related most highly to usual and highest pain unpleasantness among women, as compared with frustration among men; and (4) contrary to expectations, pain-related emotions were more strongly related to pain for men. Consistent with the sequential model of pain processing, emotional response to pain was more closely related to pain unpleasantness than to pain intensity across sex. Anxiety and frustration were the emotions most highly related to pain. The current results highlight sex differences in the experience of chronic pain and the importance of assessing a range of emotions in patients with pain.

Sleep disturbance in orofacial pain patients: pain-related or emotional distress?

Associations between pain, depression, and sleep disturbance have been documented in several chronic pain patient samples. The current study assessed the prevalence and magnitude of sleep disturbance in a sample of 128 orofacial pain patients referred for clinical evaluation and tested linkages between sleep, depression, anxiety, and pain using cross-sectional and longitudinal data. Seventy-seven percent of the patients reported reduced sleep quantity since pain onset. In cross-sectional analyses, reduced sleep quantity was associated with depression and pain. Reduced sleep quality was associated with negative affect. Longitudinally, initial depression and pain predicted sleep at time two and initial pain predicted negative affect. Sleep did not predict pain. Results support the hypothesis that pain, rather than sleep disturbance, increases negative affect across time, whereas negative affect is more a cause of concurrent reduced sleep quality than is pain. The results highlight the importance of assessing for sleep disturbance in orofacial pain patients.