Lindsay L. Kindler

Risk Factors Predicting the Development of Widespread Pain From Chronic Back or Neck Pain

UNLABELLED Emerging evidence suggests that some individuals with regional pain disorders go on to develop chronic widespread pain (CWP). However, the mechanism behind this transition and the nature of risk factors that predispose a person to develop CWP remain to be elucidated. The purpose of this study was to describe the frequency with which participants with chronic back or neck pain develop CWP and to determine the risk factors associated with this development. In a sample of 512 individuals, we found that nearly a quarter (22.6%) of subjects who presented with regional back or neck pain in 2001/2002 had developed CWP by 2007. Logistic regression indicated that 7 factors were associated with the transition to CWP: moderate or severe pain intensity, female gender, history of abuse, family history of CWP, severe interference with general activity, having 1 or more central sensitivity syndromes, and using more pain management strategies. History of abuse was not significant in multivariate analysis. Notably, number of depressive symptoms endorsed, pain duration, age, body mass index, number of medication classes used, and receipt of disability benefits were not significantly associated with this transition. PERSPECTIVE This study offers insight into risk factors associated with the development of CWP. This information not only offers clues as to the mechanism behind the expansion of pain sensitivity from a regional pain locus to a widespread pain disorder but also provides insight as to how clinicians might mitigate this transition.

Vitamin D, Race, and Experimental Pain Sensitivity in Older Adults with Knee Osteoarthritis

OBJECTIVE Low circulating serum levels of 25-hydroxyvitamin D (referred to hereafter as vitamin D) have been correlated with many health conditions, including chronic pain. Recent clinical practice guidelines define vitamin D levels <20 ng/ml as deficient and levels of 21-29 ng/ml as insufficient. Vitamin D insufficiency, including the most severe levels of deficiency, is more prevalent in black Americans. Ethnic and race group differences have been reported in both clinical and experimental pain, with black Americans reporting increased pain. The purpose of this study was to examine whether variations in vitamin D levels contribute to race differences in knee osteoarthritis pain. METHODS The sample consisted of 94 participants (74% women), including 45 blacks and 49 whites with symptomatic knee osteoarthritis. Their average age was 55.8 years (range 45-71 years). Participants completed a questionnaire on knee osteoarthritis symptoms and underwent quantitative sensory testing, including measures of sensitivity to heat-induced and mechanically induced pain. RESULTS Blacks had significantly lower levels of vitamin D compared to whites, demonstrated greater clinical pain, and showed greater sensitivity to heat-induced and mechanically induced pain. Low levels of vitamin D predicted increased experimental pain sensitivity, but did not predict self-reported clinical pain. Group differences in vitamin D levels significantly predicted group differences in heat pain and pressure pain thresholds at the index knee and ipsilateral forearm. CONCLUSION These data demonstrate that race differences in experimental pain are mediated by differences in the vitamin D level. Vitamin D deficiency may be a risk factor for increased knee osteoarthritis pain in black Americans.

Sex differences in experimental and clinical pain sensitivity for patients with shoulder pain

Previous research demonstrates that men and women differ in the way that they perceive and process pain. Much of this work has been done in healthy adults with a lack of consensus in clinical pain populations. The purpose of this study was to investigate how men and women with shoulder pain differ in their experience of experimental and clinical pain and whether psychological processes differentially affect these responses. Fifty‐nine consecutive subjects (24 women, 35 men) seeking operative treatment for shoulder pain were enrolled in this study. Subjects completed self report questionnaires to assess clinical pain, catastrophizing, anxiety and depression and underwent a series of experimental pain tests consisting of pressure pain, thermal pain (threshold and tolerance), and thermal temporal summation. Results indicated that women experienced greater clinical pain and enhanced sensitivity to pressure pain. Age did not affect the observed sex differences. There were no sex differences in psychological association with experimental and clinical pain in this cohort. The relationship between clinical and experimental pressure pain was stronger in women as compared to men. These findings offer insight into the interactions between biological and psychosocial influences of pain and how these interactions vary by sex.Previous research demonstrates that men and women differ in the way that they perceive and process pain. Much of this work has been done in healthy adults with a lack of consensus in clinical pain populations. The purpose of this study was to investigate how men and women with shoulder pain differ in their experience of experimental and clinical pain and whether psychological processes differentially affect these responses. Fifty-nine consecutive subjects (24 women, 35 men) seeking operative treatment for shoulder pain were enrolled in this study. Subjects completed self report questionnaires to assess clinical pain, catastrophizing, anxiety and depression and underwent a series of experimental pain tests consisting of pressure pain, thermal pain (threshold and tolerance), and thermal temporal summation. Results indicated that women experienced greater clinical pain and enhanced sensitivity to pressure pain. Age did not affect the observed sex differences. There were no sex differences in psychological association with experimental and clinical pain in this cohort. The relationship between clinical and experimental pressure pain was stronger in women as compared to men. These findings offer insight into the interactions between biological and psychosocial influences of pain and how these interactions vary by sex.

Investigation of Central Pain Processing in Shoulder Pain: Converging Results From 2 Musculoskeletal Pain Models

UNLABELLED Recent reports suggest deficits in conditioned pain modulation (CPM) and enhanced suprathreshold heat pain response (SHPR) potentially play a role in the development of chronic pain. The purpose of this study was to investigate whether central pain processing was altered in 2 musculoskeletal shoulder pain models. The goals of this study were to determine whether central pain processing: 1) differs between healthy subjects and patients with clinical shoulder pain; 2) changes with induction of exercise-induced muscle pain; and 3) changes 3 months after shoulder surgery. Fifty-eight patients with clinical shoulder pain and 56 age- and sex-matched healthy subjects were included in these analyses. The healthy cohort was examined before inducing EIMP, and 48 and 96 hours later. The clinical cohort was examined before shoulder surgery and 3 months later. CPM did not differ between the cohorts, however; SHPR was elevated for patients with shoulder pain compared to healthy controls. Induction of acute shoulder pain with EIMP resulted in increased shoulder pain intensity but did not change CPM or SHPR. Three months following shoulder surgery, clinical pain intensity decreased but CPM was unchanged from preoperative assessment. In contrast, SHPR was decreased and showed values comparable with healthy controls at 3 months. Therefore, the present study suggests that: 1) clinical shoulder pain is associated with measurable changes in central pain processing; 2) exercise-induced shoulder pain did not affect measures of central pain processing; and 3) elevated SHPR was normalized with shoulder surgery. Collectively our findings support neuroplastic changes in pain modulation were associated with decreases in clinical pain intensity only, and could be detected more readily with thermal stimuli. PERSPECTIVE Longitudinal studies involving quantitative sensory testing are rare. In exploring 2 musculoskeletal shoulder pain models (exercise-induced muscle pain and surgical pain), conditioned pain modulation was unchanged from pre- to post-assessment in both models. Suprathreshold heat pain response decreased after shoulder surgery and was comparable to healthy controls, suggesting this measure may be sensitive to decreases in clinical pain intensity.

Drug Response Profiles to Experimental Pain are Opioid and Pain Modality Specific

UNLABELLED Given our limited ability to predict analgesic efficacy, further research is needed to understand factors influencing analgesic response patterns. The aim of this study was to better understand the relationship between morphine and butorphanol analgesic efficacy tested against multiple pain modalities within the same individuals. Participants included healthy men (n = 72) and women (n = 67) who underwent thermal, pressure, and ischemic experimental pain testing before and after the double-blind administration of morphine and butorphanol during separate testing sessions. Factor analysis revealed 6 factors with analgesic effects grouped primarily by pain modality and specific to either morphine or butorphanol. Hierarchical cluster analysis of individual factor scores led to 4 distinct drug response profiles. Three groups displayed exceptional analgesic efficacy produced by 1 type of opioid on 1 pain stimulus modality, whereas the fourth drug response profile was characterized by average analgesic efficacy across all pain modalities for both opioids. These findings suggest that opioids with varying efficacy at the μ and κ receptors produce independent effects on unique pain mechanisms and that individual responsiveness for some is dependent on pain mechanism and opioid type, although a subset of the population is moderately responsive to opioids regardless of efficacy of receptor binding or predominant pain mechanism being activated. PERSPECTIVE This investigation provides a foundation for understanding patterns of opioid efficacy in varying types of pain. Our findings suggest that opioid response patterns are more complex than originally thought with about half of individuals exhibiting opioid and pain modality specific analgesic response profiles.

Thermal and Pressure Pain Sensitivity in Patients with Unilateral Shoulder Pain: Comparison of Involved and Uninvolved Sides

STUDY DESIGN Cross-sectional. BACKGROUND In the examination of patients with unilateral shoulder pain, pain provocation testing to compare the involved and uninvolved sides has been considered useful. However, side-to-side comparisons of experimental pain sensitivity in patients with unilateral shoulder pain are not widely reported in the literature. OBJECTIVES To compare experimental pain sensitivity between the involved and uninvolved sides in patients with unilateral shoulder pain. METHODS In consecutive patients seeking operative treatment for shoulder pain, sensitivity measures of bilateral pressure pain threshold at the shoulder and forearm, and thermal pain threshold, tolerance, and temporal summation at the forearm, were examined. Pressure sensitivity was tested with a Fischer pressure algometer, and thermal sensitivity with a computer-controlled Medoc neurosensory analyzer. The involved and uninvolved sides were compared with an analysis of variance. Influence of sex and location of testing were considered as covariates in the analysis. RESULTS Fifty-nine consecutively recruited participants completed experimental pain sensitivity testing. Participants reported significantly lower pressure pain thresholds in the involved side compared to the uninvolved side (F1,56 = 4.96, P = .030). In addition, female compared to male participants demonstrated lower pressure pain thresholds in the bilateral shoulder regions (F1,56 = 10.84, P = .002). There was no difference in thermal pain sensitivity between sides. Average clinical pain intensity was negatively correlated with pressure pain threshold at the involved local site (r = -0.284, P = .029), indicating an influence of clinical pain intensity on local pressure pain. CONCLUSION The results of this study provide evidence for higher experimental pressure pain sensitivity in the involved side of patients with unilateral shoulder pain and no difference between sides for thermal pain sensitivity. Females demonstrated higher pain sensitivity than males to pressure stimuli at the local shoulder region but not at the distal regions. Future studies should incorporate multiple stimuli when describing the pain profile of clinical populations.

Individual differences in morphine and butorphanol analgesia: a laboratory pain study.

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 response 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 (76 men/66 women), 119 non-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 postdrug 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 predrug 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 with non-Hispanic whites. For thermal pain threshold, butorphanol but not morphine analgesia was greater for African American vs non-Hispanic whites. CONCLUSIONS Findings are among the first to demonstrate race differences in a laboratory study of opioid analgesia.

Affect balance style, experimental pain sensitivity, and pain-related responses.

Objectives:Affect is neurobiologically based, influences emotions, contributes to temperamental characteristics, and can be evaluated from both state and trait perspectives. Associations between state-related positive affect (PA), negative affect (NA), and chronic pain have been investigated. However, little is known about the relationship between trait affect patterns and pain-related experiences. Affect balance style (ABS) provides a framework to assess the combined contribution of trait PA and NA. Psychological factors and experimental pain sensitivity are indicated as predictors of chronic pain onset. The current study investigated the relationship between ABS, pain sensitivity, and pain-related measures in healthy adults. Methods:Participants (n=372) completed quantitative sensory testing, pain-related questionnaires, and the Positive and Negative Affect Scale. ABS groups were categorized as Healthy (high PA, low NA), Low (low PA, low NA), Depressive (low PA, high NA), and Reactive (high PA, high NA). Z-scores were computed for 3 experimental pain measures: ischemic, pressure, and heat. Results:ABS groups significantly differed on ischemic pain sensitivity and pain-related measures. Specifically, the Healthy group demonstrated lower ischemic pain sensitivity compared with the Reactive group (P=0.02); the Depressive and Reactive groups endorsed higher somatic symptoms compared with the Healthy group (P<0.02); the Low and Depressive groups reported more physical stimuli sensitivity than the Healthy group (P<0.02); and the Reactive group indicated more passive coping strategies then the Low and Healthy groups (P=0.001). Discussion:Findings from the study suggest that among healthy adults, trait affect patterns are associated with ischemic experimental pain sensitivity and other pain-related measures.