Related Articles

Substantial evidence indicates that the experience of both clinical and experimental pain differs among ethnic groups. Specifically, African Americans generally report higher levels of clinical pain and greater sensitivity to experimentally induced pain; however, little research has examined the origins of these differences. Differences in central pain-inhibitory mechanisms may contribute to this disparity. Diffuse noxious inhibitory controls (DNIC), or counterirritation, is a phenomenon thought to reflect descending inhibition of pain signals. The current study assessed DNIC in 57 healthy young adults from two different ethnic groups: African Americans and non-Hispanic whites. Repeated assessments of the nociceptive flexion reflex (NFR) as well as ratings of electrical pain were obtained prior to, during and after an ischemic arm pain procedure (as well as a sham procedure). The DNIC condition (i.e. ischemic arm pain) produced substantial reductions in pain ratings as well as electrophysiologic measures of the NFR for all participants when compared with the sham condition (p < .001). The DNIC condition produced significantly greater reductions in verbal pain ratings among non-Hispanic whites when compared with African Americans (p = .02), while ethnic groups showed comparable reductions in NFR. The findings of this study suggest differences in endogenous pain inhibition between African Americans and non-Hispanic whites and that additional research to determine the mechanisms underlying these effects is warranted.

Perspective

This study adds to a growing literature examining ethnic differences in experimental pain perception. Our data suggest that these variations may be influenced by differences in descending inhibition.

Understanding the genetic basis of human variations in pain is critical to elucidating the molecular basis of pain sensitivity, variable responses to analgesic drugs, and, ultimately, to individualized treatment of pain and improved public health. With the help of recently accumulated knowledge and advanced technologies, pain researchers hope to gain insight into genetic mechanisms of pain and eventually apply this knowledge to pain treatment.

Perspective

We critically reviewed the published literature to examine the strength of evidence supporting genetic influences on clinical and human experimental pain. Based on this evidence and the experience of false associations that have occurred in other related disciplines, we provide recommendations for avoiding pitfalls in pain genetic research.

Sex-related influences on pain and analgesia have become a topic of tremendous scientific and clinical interest, especially in the last 10 to 15 years. Members of our research group published reviews of this literature more than a decade ago, and the intervening time period has witnessed robust growth in research regarding sex, gender, and pain. Therefore, it seems timely to revisit this literature. Abundant evidence from recent epidemiologic studies clearly demonstrates that women are at substantially greater risk for many clinical pain conditions, and there is some suggestion that postoperative and procedural pain may be more severe among women than men. Consistent with our previous reviews, current human findings regarding sex differences in experimental pain indicate greater pain sensitivity among females compared with males for most pain modalities, including more recently implemented clinically relevant pain models such as temporal summation of pain and intramuscular injection of algesic substances. The evidence regarding sex differences in laboratory measures of endogenous pain modulation is mixed, as are findings from studies using functional brain imaging to ascertain sex differences in pain-related cerebral activation. Also inconsistent are findings regarding sex differences in responses to pharmacologic and non-pharmacologic pain treatments. The article concludes with a discussion of potential biopsychosocial mechanisms that may underlie sex differences in pain, and considerations for future research are discussed.

Perspective

This article reviews the recent literature regarding sex, gender, and pain. The growing body of evidence that has accumulated in the past 10 to 15 years continues to indicate substantial sex differences in clinical and experimental pain responses, and some evidence suggests that pain treatment responses may differ for women versus men.

Pain catastrophizing is an important variable in the context of acute and chronic pain. The neurophysiological correlates of pain catastrophizing, however, have not been rigorously evaluated. We examined the relationship between trait pain catastrophizing and morning salivary cortisol levels before and following a 45-minute laboratory pain testing session in healthy, pain-free (n=22) and temporomandibular disorder (TMD) participants (n=39). We also examined whether TMD patients evidenced generalized hyperalgesia and hypercortisolism. Pain catastrophizing was associated with a flattened morning salivary cortisol profile in the context of pain testing, irrespective of pain status. Cortisol profiles did not differ between healthy and TMD participants. TMD was associated with mechanical hyperalgesia only at the masseter. These data are the first to show an association between pain catastrophizing and elevated salivary cortisol profiles in the context of standardized experimental pain testing. These findings in both healthy individuals and those with chronic orofacial pain suggest that aberrant adrenocortical responses to pain may serve as a neurophysiologic pathway by which pain catastrophizing enhances vulnerability for development of chronic pain and maintains and/or exaggerates existing pain and associated morbidity.

Perspective

Neurophysiological mechanisms by which pain catastrophizing is related to acute and chronic pain recently have come under empirical study. Understanding of these mechanisms has the unique potential to shed light on key central nervous system factors that mediate catastrophizing-pain relations and therapeutic benefits associated with changes in catastrophizing and related cognitive processes.

Aims: To test the long term cost-benefit and cost-effectiveness of the Sherbrooke model of management of subacute occupational back pain, combining an occupational and a clinical rehabilitation intervention.

Methods: A randomised trial design with four arms was used: standard care, occupational arm, clinical arm, and Sherbrooke model arm (combined occupational and clinical interventions). From the Quebec WCB perspective, a cost-benefit (amount of consequence of disease costs saved) and cost-effectiveness analysis (amount of dollars spent for each saved day on full benefits) were calculated for each experimental arm of the study, compared to standard care.

Results: At the mean follow up of 6.4 years, all experimental study arms showed a trend towards cost benefit and cost effectiveness. These results were owing to a small number of very costly cases. The largest number of days saved from benefits was in the Sherbrooke model arm.

Conclusions: A fully integrated disability prevention model for occupational back pain appeared to be cost beneficial for the workers' compensation board and to save more days on benefits than usual care or partial interventions. A limited number of cases were responsible for most of the long term disability costs, in accordance with occupational back pain epidemiology. However, further studies with larger samples will be necessary to confirm these results.

Pain-related fear and catastrophizing are important variables of consideration in an individual’s pain experience. Methodological limitations of previous studies limit strong conclusions regarding these relationships. In this follow-up study, we examined the relationships between fear of pain, pain catastrophizing, and experimental pain perception. One hundred healthy volunteers completed the Fear of Pain Questionnaire (FPQ-III), Pain Catastrophizing Scale (PCS), and Coping Strategies Questionnaire-Catastrophizing scale (CSQ-CAT) before undergoing the cold pressor test (CPT). The CSQ-CAT and PCS were completed again following the CPT, with participants instructed to complete these measures based on their experience during the procedure. Measures of pain threshold, tolerance, and intensity were collected and served as dependent variables in separate regression models. Sex, pain catastrophizing, and pain-related fear were included as predictor variables. Results of regression analyses indicated that after controlling for sex, pain-related fear was a consistently stronger predictor of pain in comparison to catastrophizing. These results were consistent when separate measures (CSQ-CAT vs. PCS) and time points (pre-task vs. “in-vivo”) of catastrophizing were used. These findings largely corroborate those from our previous study and are suggestive of the absolute and relative importance of pain-related fear in the experimental pain experience.

Perspective

Although pain-related fear has received less attention in the experimental literature than pain catastrophizing, results of the current study are consistent with clinical reports highlighting this variable as an important aspect of the experience of pain.

Women have a higher prevalence of fibromyalgia and myofascial pain than men, but sex differences in muscle pain are inconsistently detected. We examined sex differences in ratings and effects of recalled and experimentally-induced muscle pain. In Study 1 (N = 188), participants completed a questionnaire about recalled muscle pain. In Study 2 (N = 55), participants’ described muscle pain from an exercise stimulus across three days by telephone. Muscle pain ratings, self-care behaviors for muscle pain, and effects of muscle pain on activities were measured. No significant sex differences were found except that women tended to view exercise as more effective for decreasing muscle pain than men (F1, 187 = 5.43, p = .02, η2 = .03), fewer women performed exercise for induced muscle pain than men, and women’s activity interference was significantly higher than men’s at the third day post-exercise (F2, 42 = 6.54, p= .01, η2 = .14). These findings support the absence of meaningful sex differences in muscle pain ratings. However, additional investigations are needed that consider the daily activities completed by people and the prevalence and incidence of performing a wide range of self-care behaviors for pain.

Perspective: These studies support that sex differences are not present in recalled and experimentally-induced muscle pain ratings. Therefore, we must be cautious about generalizing the musculoskeletal pain literature to muscle pain. Additional research is needed to interpret potential sex differences in self-care behaviors for muscle pain and activity interference from muscle pain.

Pain-related fear and pain catastrophizing are two central psychologic factors in fear-avoidance models. Our previous studies in healthy subjects indicated that pain-related fear, but not pain catastrophizing, was associated with cold pressor pain outcomes. The current study extends previous work by investigating pain-related fear and pain catastrophizing in a group of subjects with shoulder pain, and included concurrent measures of experimental and clinical pain. Fifty nine consecutive subjects seeking operative treatment of shoulder pain were enrolled in this study (24 females, mean age = 50.4, sd = 14.9). Subjects completed validated measures of pain-related fear, pain catastrophizing, and clinical pain intensity and then underwent a cold pressor task to determine experimental pain sensitivity. Multivariate regression models used sex, age, pain-related fear, and pain catastrophizing to predict experimental pain sensitivity and clinical pain intensity. Results indicated that only pain-related fear uniquely contributed to variance in experimental pain sensitivity (beta = −.42, p < .01). In contrast, sex (beta = −.29, p = .02) and pain catastrophizing (beta = .43, p < .01) uniquely contributed to variance in clinical pain intensity. These data provide additional support for application of fear-avoidance models to subjects with shoulder pain. Our results also suggest that pain-related fear and pain catastrophizing may influence different components of the pain experience, providing preliminary support for recent theoretical conceptualizations of the role of pain catastrophizing.

The current study examined the utility of a biopsychosocial model of chronic pain, and the associations between specific pain-related beliefs, coping, and social support and both mental health and pain interference, in persons with Spinal Cord Injury (SCI) and pain. A total of 157 patients completed surveys assessing physical and psychological functioning, as well as psychosocial, demographic, and injury-related variables. Greater catastrophizing and pain-related beliefs (e.g., the belief that pain signals damage) were related with increased pain interference and poorer mental health, while coping styles (e.g., resting, asking for assistance) were related only with pain interference. Alternatively, greater perceived social support was related with better mental health. The findings are consistent with a biopsychosocial model, implicating the need to consider the impact of process and clinical variables on adjustment to chronic pain in persons with SCI.

Perspective:

This article identifies several psychosocial variables, including coping, catastrophizing, pain-related beliefs, and social support, that are related to adjustment in persons with SCI and pain. These results have implications for interventions designed to treat pain interference in persons with SCI.

Researchers have become increasingly interested in the social context of chronic pain conditions. The purpose of this article is to provide an integrated review of the evidence linking marital functioning with chronic pain outcomes including pain severity, physical disability, pain behaviors, and psychological distress. We first present an overview of existing models that identify an association between marital functioning and pain variables. We then review the empirical evidence for a relationship between pain variables and several marital functioning variables including marital satisfaction, spousal support, spouse responses to pain, and marital interaction. On the basis of the evidence, we present a working model of marital and pain variables, identify gaps in the literature, and offer recommendations for research and clinical work.

Perspective

The authors provide a comprehensive review of the relationships between marital functioning and chronic pain variables to advance future research and help treatment providers understand marital processes in chronic pain.

Functional neuroimaging has fundamentally changed our knowledge about the cerebral representation of pain. For the first time it has been possible to delineate the functional anatomy of different aspects of pain in the medial and lateral pain systems in the brain. The rapid developments in imaging methods over the past years have led to a consensus in the description of the central pain responses between different studies and also to a definition of a central pain matrix with specialized subfunctions in man. In the near future we will see studies where a systems perspective allows for a better understanding of the regulatory mechanisms in the higher-order frontal and parietal cortices. Also, pending the development of experimental paradigms, the functional anatomy of the emotional aspects of pain will become better known.

Thirty-two African American and 23 non-Hispanic White women were compared for experimental pain threshold and tolerance to thermal, ischemic, and cold pressor pain. Approximately half of each group had prior mood disorders (17 African Americans, 13 non-Hispanic Whites), though all were free of current mood disturbance. Women with prior mood disorders were less sensitive to ischemic pain than women with no prior mood disorders (p<.05), while African Americans were more sensitive to ischemic pain than non-Hispanic Whites, though only at pain tolerance (p<.001). For cold pressor pain, the effects of race were only seen in women with prior mood disorders, since African Americans with prior mood disorders were more sensitive than non-Hispanic Whites with prior mood disorders (p<.05). These results indicate that experimental pain sensitivity in women is influenced by both race and histories of mood disorders.

Perspective:

We examined the association of race and histories of mood disorders with experimental pain sensitivity in an exclusively female sample. Our findings for racial differences in pain sensitivity may have implications for greater clinical pain in African American women. Persistent disturbance in pain modulatory mechanisms in women with a history of mood disorders may also have implications for the development of subsequent mood disturbances.

The relationship between physical activity and central nervous system mechanisms of pain in fibromyalgia (FM) is unknown. This study determined whether physical activity was predictive of brain responses to experimental pain in FM using functional magnetic resonance imaging (fMRI). Thirty-four participants (n=16 FM; n=18 Control) completed self-report and accelerometer measures of physical activity and underwent fMRI of painful heat stimuli. In FM patients, positive relationships (p<0.005) between physical activity and brain responses to pain were observed in the dorsolateral prefrontal cortex, posterior cingulate cortex, and the posterior insula, regions implicated in pain regulation. Negative relationships (p<0.005) were found for the primary sensory and superior parietal cortices, regions implicated in the sensory aspects of pain. Greater physical activity was significantly (p<0.05) associated with decreased pain ratings to repeated heat stimuli for FM patients. A similar non-significant trend was observed in controls. In addition, brain responses to pain were significantly (p<0.005) different between FM patients categorized as `low' active and those categorized as `high' active. In controls, positive relationships (p<0.005) were observed in the lateral prefrontal, anterior cingulate and superior temporal cortices and the posterior insula. Our results suggest an association between measures of physical activity and central nervous system processing of pain.

PERSPECTIVE

Our data suggest that brain responses to pain represent a dynamic process where perception and modulation co-occur and that physical activity plays a role in balancing these processes. Physically active FM patients appear to maintain their ability to modulate pain while those who are less active do not.

Tobacco addiction and chronic pain represent two highly prevalent and comorbid conditions that engender substantial burdens upon individuals and systems. Although interrelations between pain and smoking have been of clinical and empirical interest for decades, research on the topic of pain, nicotine, and tobacco smoking has increased dramatically over the past five years. We conceptualize the interaction of pain and smoking as a prototypical example of the biopsychosocial model. Accordingly, the current review extrapolated from behavioral, cognitive, affective, biomedical, and social perspectives to propose causal mechanisms that may contribute to the observed comorbidity between these two conditions. Research in the broad area of pain and smoking was first dichotomized into investigations of either "effects of smoking on pain" or "effects of pain on smoking." We then integrated the extant literature to present a reciprocal model of pain and smoking that is hypothesized to interact in the manner of a positive feedback loop, resulting in greater pain, increased smoking, and the maintenance of tobacco addiction. Finally, we proposed directions for future research, and discussed clinical implications for smokers with comorbid pain disorders. We observed modest evidence to support the notions that smoking may be a risk factor in the multifactorial etiology of some chronically painful conditions, and that the experience of pain may come to serve as a potent motivator of smoking. We also found that whereas animal studies yielded consistent support for direct pain-inhibitory effects of nicotine and tobacco smoke, results from human studies were much less consistent. Future research in the emerging area of pain and smoking has the potential to inform theoretical and clinical applications with respect to tobacco smoking, chronic pain, and their comorbid presentation.

There is limited research describing the patterns of healthcare utilization in adolescents with chronic pain. This study describes healthcare utilization in a clinical chronic pain sample, and compares the patterns of service use of this group to a community sample with intermittent pain complaints. We also investigated demographic and clinical factors that predicted healthcare visits and medication use in the clinical sample. Data on 117 adolescents (aged 12-18; n=59 clinical pain sample, n=58 community) were collected. Caregivers and adolescents reported on sociodemographics, medical visits, current medications, pain, activity limitations, and depression. As hypothesized, the clinical pain sample had higher rates of healthcare consultation on all types of medical visits (general, specialty care, complementary medicine, mental health, OT/PT), and higher medication use compared to the community sample. Regression analyses revealed that higher annual income, greater pain frequency, and higher levels of caregiver reported activity limitations were associated with a greater number of healthcare visits for the total sample. Within the clinical pain sample, higher pain frequency and greater activity limitations (caregiver-report) predicted more specialty care visits. Additionally, higher income and greater levels of depressive symptoms predicted a higher number of prescribed medications.

Perspective

This study contributes to the limited available data on health service and medication use in a clinical chronic pain sample versus a community sample of adolescents. We also identify clinical factors (pain frequency, parent-reported activity limitations, depressive symptoms) and demographic factors (gender, income) associated with healthcare utilization.

Deep visceral pain is frequent and presents major challenges in pain management, since its pathophysiology is still poorly understood. One way to optimize treatment of visceral pain is to improve knowledge of the mechanisms behind the pain and the mode of action of analgesic substances. This can be achieved through standardized experimental human pain models. Experimental pain models in healthy volunteers are advantageous for evaluation of analgesic action, as this is often difficult to assess in the clinic because of confounding factors such as sedation, nausea and general malaise. These pain models facilitate minimizing the gap between knowledge gained in animal and human clinical studies. Combining experimental pain studies and pharmacokinetic studies can improve understanding of the pharmacokinetic-pharmacodynamic relationship of analgesics and, thus, provide valuable insight into optimal clinical treatment of visceral pain. To improve treatment of visceral pain, it is important to study the underlying mechanisms of pain and the action of analgesics used for its treatment. An experimental pain model activates different modalities and can be used to investigate the mechanism of action of different analgesics in detail. In combination with pharmacokinetic studies and objective assessment such as electroencephalography, new information regarding a given drug substance and its effects can be obtained. Results from experimental human visceral pain research can bridge the gap in knowledge between animal studies and clinical condition in patients suffering from visceral pain, and thus constitute the missing link in translational pain research.

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.

Although large interindividual differences in pain exist, the underlying factors that contribute to these variations remain poorly understood. Consequently, being able to accurately explain variability in pain ratings in terms of its contributing factors could provide insights into developing a better understanding of individual differences in pain experience. In the present investigation, we show that a significant portion of the variability in experimental heat pain ratings may be predicted using simple quantitative sensory testing and a series of psychological questionnaires including State Trait and Anxiety Inventory (STAI), Center for Epidemiologic Studies – Depression Scale (CES-D), and Positive and Negative Affect Schedule – Expanded form (PANAS-X). A factor analysis was used to reduce individual predictors into sets of composite predictive factors. A multifactorial model that was generated from these factors can reliably predict a significant amount of the variability in heat pain sensitivity ratings (r2 = 0.537, p=0.027). Moreover, individual variables including heat pain thresholds and self-assessment of pain sensitivity were found to be poor predictors of heat pain sensitivity. Taken together, these results suggest that a variety of factors underlie individual differences in pain experience, and that a reliable model for predicting pain should be constructed from a combination of these factors.

Perspective

The present study provides a way to predict subjects’ experimental heat pain sensitivity using a multifactorial model generated from a combination of sensory and psychological factors. Future application of such a model in the studies of clinical pain could potentially improve the quality of care provided for patients in pain.

The aim of this article is to report the development and preliminary testing of a prototype computerized adaptive test of chronic pain (CHRONIC PAIN-CAT) conducted in two stages: 1) evaluation of various item selection and stopping rules through real data simulated administrations of CHRONIC PAIN-CAT; 2) a feasibility study of the actual prototype CHRONIC PAIN-CAT assessment system conducted in a pilot sample. Item calibrations developed from a US general population sample (N=782) were used to program a pain severity and impact item bank (k=45) and real data simulations were conducted to determine a CAT stopping rule. The CHRONIC-PAIN CAT was programmed on a tablet PC using QualityMetric's Dynamic Health Assessment (DYHNA®) software and administered to a clinical sample of pain sufferers (n=100). The CAT was completed in significantly less time than the static (full item bank) assessment (p<.001). On average, 5.6 items were dynamically administered by CAT to achieve a precise score. Scores estimated from the two assessments were highly correlated (r=.89) and both assessments discriminated across pain severity levels (p<.001, RV=.95). Patients’ evaluations of the CHRONIC PAIN-CAT were favourable.

Perspective

This report demonstrates that the CHRONIC PAIN-CAT is feasible for administration in a clinic. The application has the potential to improve pain assessment and help clinicians manage chronic pain.

Because fibromyalgia (FM) patients frequently report activity-dependent deep tissue pains, impulse input from painful body regions may be relevant for their musculoskeletal complaints. In addition, peripheral impulse input may induce and maintain thermal and mechanical hyperalgesia of FM patients. If so, activity and rest may alternately enhance and diminish intensity of FM pain. However, the effects of exercise on pain are ambiguous in studies of FM. Whereas exercise-only studies demonstrated increased pain and hyperalgesia during and after physical activity, some exercise studies that included rest periods resulted in decreased FM pain and increased function. To further clarify these effects, we examined the effects of alternating exercise with rest on clinical pain and thermal/mechanical hyperalgesia of 34 FM patients and 36 age-matched healthy controls (NC). Using an ergometer, all subjects performed arm exercise to exhaustion twice alternating with 15 min rest periods. Although strenuous muscle activity was reported as painful by most FM subjects, overall clinical pain consistently decreased during the rest periods. Additionally, FM subjects’ pain sensitivity to mechanical pressure decreased after each exercise and rest session.

Conclusion

Alternating strenuous exercise with brief rest periods not only decreased overall clinical pain of FM subjects but also their mechanical hyperalgesia. No prolonged worsening of overall FM pain and hyperalgesia occurred despite vigorous muscle activity. Our findings contribute further evidence that FM pain and hyperalgesia are at least partially maintained by muscle impulse input and that some types of exercises may be beneficial for FM.

Perspective

FM is a pain-amplification syndrome that depends at least in part on peripheral tissue impulse input. Whereas muscle activity increased overall pain, short rest periods produced analgesic effects.

Substantial literature suggests that diverse biological, psychological, and sociocultural mechanisms account for differences by race and ethnicity in the experience, epidemiology, and management of pain. Many studies have examined differences between Whites and minority populations, but American Indians (AIs), Alaska Natives (ANs), and Aboriginal peoples of Canada have been neglected both in studies of pain and in efforts to understand its bio-psychosocial and cultural determinants. This article reviews the epidemiology of pain and identifies factors that may affect clinical assessment and treatment in these populations. We searched for peer-reviewed articles focused on pain in these populations, using PubMed, CINAHL, Cochrane, and the University of New Mexico Native Health Database. We identified 28 articles published 1990-2009 in 3 topic areas: epidemiology of pain, pain assessment and treatment, and healthcare utilization. A key finding is that AI/ANs have a higher prevalence of pain symptoms and painful conditions than the U.S. general population. We also found evidence for problems in provider-patient interactions that affect clinical assessment of pain, as well as indications that AI/AN patients frequently use alternative modalities to manage pain. Future research should focus on pain and comorbid conditions and develop conceptual frameworks for understanding and treating pain in these populations.

Perspective

We reviewed the literature on pain in AI/ANs and found a high prevalence of pain and painful conditions, along with evidence of poor patient-provider communication. We recommend further investigation of pain and comorbid conditions and development of conceptual frameworks for understanding and treating pain in this population.

There are many types of pain assessments available to researchers conducting clinical trials, ranging from simple, single-item Visual Analog Scale (VAS) questions through extensive, multidimensional inventories. The primary question addressed in this survey of top-tier medical journals was: Which pain assessments are most commonly used in trials? Articles addressing chronic musculoskeletal pain in clinical trials were identified in seven major medical journals for the year 2003. A total of 50 studies (total original research articles reviewed: 1,476) met selection criteria, and from these we identified 28 types of pain assessments. Selected studies were classified according to the dimensions of pain assessed, the type of scale and descriptors/anchors used, and the reporting period specified. The most frequently used assessments were the single-item VAS scale and the Numeric Rating Scale (NRS); multidimensional inventories were used infrequently. There was considerable variability in the instructions patients received about the period to consider when evaluating their pain, and many studies provided only cursory information about their assessments in the methods. Overall, it appears that clinical trials utilize simple measures of pain and that there is no widely accepted standard for clinical pain assessment that would facilitate comparison of outcomes across trials.

Perspective

This review highlights the heterogeneity of pain outcome measures used and the abundance of single-item measures in clinical trials. While there are many pain outcome measures available to clinical researchers, more consistency in the field should be encouraged so that results between studies can be compared.

Pain represents the major motivating factor for which individuals seek healthcare, and pain responses are characterized by substantial inter-individual differences. Increasing evidence suggests that genetic factors contribute significantly to individual differences in responses to both clinical and experimental pain. The purpose of this review article was to summarize the current literature regarding genetic contributions to pain, highlighting findings relevant to oral pain where available. A brief discussion of methodologic considerations is followed by a review of findings regarding genetic influences on clinical pain. Next, the literature examining genetic contributions to experimental pain responses is presented, emphasizing genetic associations that have been replicated in multiple cohorts. It is hoped that an enhanced understanding of genetic contributions to pain responses will ultimately improve diagnosis and treatment of clinical pain conditions.

Background

Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches.

Discussion

Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient.

An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention.

Summary

The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed.

Introduction

Fibromyalgia (FM), characterized by wide-spread diffuse pain and sensory abnormalities, is associated with elevated indices of distress and pain-related catastrophizing compared to both pain-free samples and those with chronic pain conditions. Catastrophizing is a pervasive negative mental set, and is a strong predictor of negative pain-related outcomes such as clinical pain intensity, and physical disability. Situational catastrophizing, measured in the context of experimentally-induced pain, is strongly related to enhanced pain sensitivity, a core aspect of the pathophysiology of fibromyalgia. However, little is known regarding the temporal course of the association between catastrophizing and pain-related "outcomes". Most studies involve only static assessments of pain and catastrophizing at a single time point, which provides little insight into the direction of the observed associations. We sought to investigate the temporal relationships between catastrophizing and indices of both clinical pain (substudy 1) and experimentally-induced pain (substudy 2) in a larger randomized controlled longitudinal trial.

Methods

Fifty-seven patients with FM completed catastrophizing, depression, and pain questionnaires as well as laboratory cold pressor pain testing at baseline, post-intervention and three month follow-up during a lifestyle physical activity study. Cross-lagged panel analyses were used to address these temporal relationships.

Results

In substudy 1, analyses revealed that pre-to-post changes in dispositional catastrophizing ratings prospectively accounted for unique variance in subsequent post-to-follow-up changes in clinical pain ratings (p = 0.005), while pre-to-post changes in pain ratings did not account for unique variance in post-to-follow-up changes in catastrophizing ratings. An identical pattern was observed experimentally in substudy 2, with pre-to-post changes in situational catastrophizing ratings prospectively accounting for unique variance in subsequent post-to-follow-up changes in experimental pain ratings (p = 0.014), while pre-to-post changes in pain ratings did not account for unique variance in post-to-follow-up changes in catastrophizing ratings. Specifically, initial alterations in catastrophizing were associated with subsequent alterations in clinical and experimentally induced pain. Controlling for levels of depression did not affect the results.

Conclusions

These findings provide empirical evidence that catastrophizing processes might precede and contribute to subsequent alterations in the pain experience for FM patients.

Trial Registration

clinicaltrials.gov: NCT00383084.