Showing papers in "Pain in 2015"
Heidelberg University1, University of Marburg2, Queen Mary University of London3, University of Leeds4, Rutgers University5, University of New South Wales6, University of Münster7, Aarhus University8, Columbia University9, University of Chieti-Pescara10, Norwegian University of Science and Technology11, Karolinska Institutet12, Université catholique de Louvain13, University of Sydney14, University of Western Australia15, University of Dundee16, Katholieke Universiteit Leuven17, Maastricht University18, National Yang-Ming University19
TL;DR: The IASP Task Force, which comprises pain experts from across the globe, has developed a new and pragmatic classification of chronic pain for the upcoming 11th revision of the International Classification of Diseases, termed “multiple parenting.”
Abstract: Chronic pain has been recognized as pain that persists past normal healing time5 and hence lacks the acute warning function of physiological nociception.35 Usually pain is regarded as chronic when it lasts or recurs for more than 3 to 6 months.29 Chronic pain is a frequent condition, affecting an estimated 20% of people worldwide6,13,14,18 and accounting for 15% to 20% of physician visits.25,28 Chronic pain should receive greater attention as a global health priority because adequate pain treatment is a human right, and it is the duty of any health care system to provide it.4,13
The current version of the International Classification of Diseases (ICD) of the World Health Organization (WHO) includes some diagnostic codes for chronic pain conditions, but these diagnoses do not reflect the actual epidemiology of chronic pain, nor are they categorized in a systematic manner. The ICD is the preeminent tool for coding diagnoses and documenting investigations or therapeutic measures within the health care systems of many countries. In addition, ICD codes are commonly used to report target diseases and comorbidities of participants in clinical research. Consequently, the current lack of adequate coding in the ICD makes the acquisition of accurate epidemiological data related to chronic pain difficult, prevents adequate billing for health care expenses related to pain treatment, and hinders the development and implementation of new therapies.10,11,16,23,27,31,37
Responding to these shortcomings, the International Association for the Study of Pain (IASP) contacted the WHO and established a Task Force for the Classification of Chronic Pain. The IASP Task Force, which comprises pain experts from across the globe,19 has developed a new and pragmatic classification of chronic pain for the upcoming 11th revision of the ICD. The goal is to create a classification system that is applicable in primary care and in clinical settings for specialized pain management.
A major challenge in this process was finding a rational principle of classification that suits the different types of chronic pain and fits into the general ICD-11 framework. Pain categories are variably defined based on the perceived location (headache), etiology (cancer pain), or the primarily affected anatomical system (neuropathic pain). Some diagnoses of pain defy these classification principles (fibromyalgia).
This problem is not unique to the classification of pain, but exists throughout the ICD. The IASP Task Force decided to give first priority to pain etiology, followed by underlying pathophysiological mechanisms, and finally the body site. Developing this multilayered classification was greatly facilitated by a novel principle of assigning diagnostic codes in ICD-11, termed “multiple parenting.” Multiple parenting allows the same diagnosis to be subsumed under more than 1 category (for a glossary of ICD terms refer to Table Table1).1). Each diagnosis retains 1 category as primary parent, but is cross-referenced to other categories that function as secondary parents.
Table 1
Glossary of ICD-11 terms.
The new ICD category for “Chronic Pain” comprises the most common clinically relevant disorders. These disorders were divided into 7 groups (Fig. (Fig.1):1): (1) chronic primary pain, (2) chronic cancer pain, (3) chronic posttraumatic and postsurgical pain, (4) chronic neuropathic pain, (5) chronic headache and orofacial pain, (6) chronic visceral pain, and (7) chronic musculoskeletal pain. Experts assigned to each group are responsible for the definition of diagnostic criteria and the selection of the diagnoses to be included under these subcategories of chronic pain. Thanks to Bedirhan Ustun and Robert Jakob of the WHO, these pain diagnoses are now integrated in the beta version of ICD-11 (http://id.who.int/icd/entity/1581976053). The Task Force is generating content models for single entities to describe their clinical characteristics. After peer review overseen by the WHO Steering Committee,39 the classification of chronic pain will be voted into action by the World Health Assembly in 2017.
Figure 1
Organizational chart of Task Force, IASP, and WHO interactions. The IASP Task Force was created by the IASP council and its scope defined in direct consultation of the chairs (R.D.T. and W.R.) with WHO representatives in 2012. The Task Force reports to ...
2. Classification of chronic pain
Chronic pain was defined as persistent or recurrent pain lasting longer than 3 months. This definition according to pain duration has the advantage that it is clear and operationalized.
Optional specifiers for each diagnosis record evidence of psychosocial factors and the severity of the pain. Pain severity can be graded based on pain intensity, pain-related distress, and functional impairment.
2.1. Chronic primary pain
Chronic primary pain is pain in 1 or more anatomic regions that persists or recurs for longer than 3 months and is associated with significant emotional distress or significant functional disability (interference with activities of daily life and participation in social roles) and that cannot be better explained by another chronic pain condition. This is a new phenomenological definition, created because the etiology is unknown for many forms of chronic pain. Common conditions such as, eg, back pain that is neither identified as musculoskeletal or neuropathic pain, chronic widespread pain, fibromyalgia, and irritable bowel syndrome will be found in this section and biological findings contributing to the pain problem may or may not be present. The term “primary pain” was chosen in close liaison with the ICD-11 revision committee, who felt this was the most widely acceptable term, in particular, from a nonspecialist perspective.
2,418 citations
TL;DR: Although significant variability remains in this literature, this review provides guidance regarding possible average rates of opioid misuse and addiction and also highlights areas in need of further clarification.
Abstract: Opioid use in chronic pain treatment is complex, as patients may derive both benefit and harm. Identification of individuals currently using opioids in a problematic way is important given the substantial recent increases in prescription rates and consequent increases in morbidity and mortality. The present review provides updated and expanded information regarding rates of problematic opioid use in chronic pain. Because previous reviews have indicated substantial variability in this literature, several steps were taken to enhance precision and utility. First, problematic use was coded using explicitly defined terms, referring to different patterns of use (ie, misuse, abuse, and addiction). Second, average prevalence rates were calculated and weighted by sample size and study quality. Third, the influence of differences in study methodology was examined. In total, data from 38 studies were included. Rates of problematic use were quite broad, ranging from <1% to 81% across studies. Across most calculations, rates of misuse averaged between 21% and 29% (range, 95% confidence interval [CI]: 13%-38%). Rates of addiction averaged between 8% and 12% (range, 95% CI: 3%-17%). Abuse was reported in only a single study. Only 1 difference emerged when study methods were examined, where rates of addiction were lower in studies that identified prevalence assessment as a primary, rather than secondary, objective. Although significant variability remains in this literature, this review provides guidance regarding possible average rates of opioid misuse and addiction and also highlights areas in need of further clarification.
1,046 citations
TL;DR: There are significant mediating effects of self-efficacy, psychological distress, and fear, which underpins the direct targeting of these constructs in treatment in people with low back pain or neck pain.
Abstract: Disability is an important outcome from a clinical and public health perspective. However, it is unclear how disability develops in people with low back pain or neck pain. More specifically, the mechanisms by which pain leads to disability are not well understood. Mediation analysis is a way of investigating these mechanisms by examining the extent to which an intermediate variable explains the effect of an exposure on an outcome. This systematic review and meta-analysis aimed to identify and examine the extent to which putative mediators explain the effect of pain on disability in people with low back pain or neck pain. Five electronic databases were searched. We found 12 studies (N = 2961) that examined how pain leads to disability with mediation analysis. Standardized regression coefficients (β) of the indirect and total paths were pooled. We found evidence to show that self-efficacy (β = 0.23, 95% confidence interval [CI] = 0.10 to 0.34), psychological distress (β = 0.10, 95% CI = 0.01 to 0.18), and fear (β = 0.08, 95% CI = 0.01 to 0.14) mediated the relationship between pain and disability, but catastrophizing did not (β = 0.07, 95% CI = -0.06 to 0.19). The methodological quality of these studies was low, and we highlight potential areas for development. Nonetheless, the results suggest that there are significant mediating effects of self-efficacy, psychological distress, and fear, which underpins the direct targeting of these constructs in treatment.
462 citations
TL;DR: Preoperative TS level correlated with the postoperatively pain intensity and may be a preoperative mechanistic predictor for the development of chronic postoperative pain in patients with osteoarthritis after TKR.
Abstract: Patients with knee osteoarthritis demonstrate decreased pressure pain thresholds (PPTs), facilitated temporal summation (TS) of pain, and decreased conditioned pain modulation (CPM) compared with healthy controls. This study aimed to correlate preoperative PPTs, TS, and CPM with the development of chronic postoperative pain after total knee replacement (TKR) surgery. Knee pain intensity (visual analog scale [VAS]: 0-10), PPTs, TS, and CPM were collected before, 2 months, and 12 months after TKR. Patients were divided into a low-pain (VAS < 3) and a high-pain (VAS ≥ 3) group based on their VAS 12 months after TKR. The high-pain group (N = 17) had higher pain intensities compared with the low-pain group (N = 61) before surgery (P = 0.009) and 12 months after surgery (P < 0.001). The PPTs of the low-pain groups were normalized for all measurement sites comparing presurgery with 12 months postsurgery (P < 0.05, contralateral arm: P = 0.059), which was not the case for the high-pain group. The low-pain group showed a functional inhibitory CPM preoperatively and 12 months postoperatively (P < 0.05), which was not found in the high-pain group. The high-pain group had higher facilitated TS preoperatively and 12 months postoperatively compared with the low-pain group (P < 0.05). Preoperative TS level correlated to 12-month postoperative VAS (R = 0.240, P = 0.037). Patients who developed moderate-to-severe pain had pronociceptive changes compared with patients who developed mild pain postsurgery. Preoperative TS level correlated with the postoperative pain intensity and may be a preoperative mechanistic predictor for the development of chronic postoperative pain in patients with osteoarthritis after TKR.
277 citations
TL;DR: It is found that placebo responses have increased considerably over this period, but drug responses have remained stable, leading to diminished treatment advantage, driven by studies conducted in the United States.
Abstract: Recent failures of clinical trials of novel analgesics designed to treat neuropathic pain have led to much speculation about the underlying reasons. One often discussed possibility is that the placebo response in these trials has increased in recent years, leading to lower separation between the drug and placebo arms. Whether this has indeed occurred has not yet been adequately addressed. Here, we extracted data from published randomized controlled trials (RCTs) of drugs for the treatment of chronic neuropathic pain over the years 1990 to 2013. We find that placebo responses have increased considerably over this period, but drug responses have remained stable, leading to diminished treatment advantage. This trend has been driven by studies conducted in the United States. Consideration of participant and study characteristics revealed that in the United States but not elsewhere, RCTs have increased in study size and length. These changes are associated with larger placebo response. Analysis of individual RCT time courses showed different kinetics for the treatment vs placebo responses, with the former evolving more quickly than the latter and plateauing, such that maximum treatment advantage was achieved within 4 weeks.
230 citations
TL;DR: It is concluded that sleep problems significantly increase the risk for reduced pain tolerance, and the need to improve sleep among patients with chronic pain, and vice versa, should be an important agenda for future research.
Abstract: Sleep problems and pain are major public health concerns, but the nature of the association between the 2 conditions is inadequately studied. The aim of this study was to determine whether a range of sleep measures is associated with experimental increased pain sensitivity. A cross-sectional large population-based study from 2007 to 2008, the Tromso 6 study, provided data from 10,412 participants (age: mean [SD], 58 [13] years; 54% women). Self-reported sleep measures provided information on sleep duration, sleep onset latency (SOL), and sleep efficiency, as well as frequency and severity of insomnia. The main outcome measure was pain sensitivity tests, including assessment of cold-pressor pain tolerance. We found that all sleep parameters, except sleep duration, were significantly associated with reduced pain tolerance. Both the frequency and severity of insomnia, in addition to SOL and sleep efficiency, were associated with pain sensitivity in a dose-response manner. Adjusting for demographics and psychological distress reduced the strengths of the hazard ratios, but most associations remained significant in the fully adjusted models. There was also a synergistic interaction effect on pain tolerance when combining insomnia and chronic pain. We conclude that sleep problems significantly increase the risk for reduced pain tolerance. Because comorbid sleep problems and pain have been linked to elevated disability, the need to improve sleep among patients with chronic pain, and vice versa, should be an important agenda for future research.
219 citations
TL;DR: The social communication model of pain provides an inclusive framework for organizing and considering these facets and their relationships and provides necessary domains to be attended to in the education of researchers and practitioners.
Abstract: Clinicians and researchers are challenged to understand the dynamic interplay among biological, psychological, and social determinants of pain. The social communication model,2,8 (Fig. 1), provides an inclusive framework for organizing and considering these facets and their relationships. Understanding any episode of pain, acute or chronic, requires grasping the broad picture and details at biological, psychological, and social levels of analysis. The social communication model of pain specifi es necessary domains to be attended to in the education of researchers and practitioners.1,16
192 citations
TL;DR: There are insufficient data to support the FLACC scale for use in all circumstances and populations to which is currently applied, and recommendations regarding appropriate use of the scale are provided.
Abstract: The Face, Legs, Activity, Cry and Consolability (FLACC) scale is one of the most widely used behavioural observation pain scales. However, the psychometrics of the scale have not been adequately summarised and evaluated to provide clear recommendations regarding its use. The aim of this study was to rigorously evaluate the reliability, validity, feasibility, and utility of the scale for clinical and research purposes and provide recommendations regarding appropriate use of the scale. Databases searched were MEDLINE, CINAHL, Embase, PsycINFO (using the Ovid, PubMed, and Ebscohost platforms), The Cochrane Database of Systematic reviews and Cochrane Controlled Trials, and Google Scholar. Psychometric evaluation studies reporting feasibility, reliability, validity, or utility data for the FLACC scale applied to children (birth to 18 years) and randomised controlled trials (RCT) using the FLACC scale to measure a study outcome in infants and children. Data extraction included study design, population demographics, and psychometric data. Analysis involved in this study are quality assessment of the psychometric evaluation studies and the RCTs using the COSMIN checklist and the Jadad scale, respectively, and narrative synthesis of all results. Twenty-five psychometric evaluations studies and 52 RCTs were included. The study population, circumstances, and quality of the studies varied greatly. Sufficient data addressing postoperative pain assessment in infants and children exist. Some positive data support the psychometrics of the scale used to assess postoperative pain in children with cognitive impairment. Limited and conflicting data addressing procedural pain assessment exist. Content validity and scale feasibility have had limited psychometric evaluation. There are insufficient data to support the FLACC scale for use in all circumstances and populations to which is currently applied.
191 citations
TL;DR: Both patient- and treatment-related risk factors predicted PPBCS, and identifying patients at risk may facilitate targeted intervention.
Abstract: Previous studies have reported that 15% to 25% of patients treated for breast cancer experience long-term moderate-to-severe pain in the area of surgery, potentially lasting for several years. Few prospective studies have included all potential risk factors for the development of persistent pain after breast cancer surgery (PPBCS). The aim of this prospective cohort study was to comprehensively identify factors predicting PPBCS. Patients scheduled for primary breast cancer surgery were recruited. Assessments were conducted preoperatively, the first 3 days postoperatively, and 1 week, 6 months, and 1 year after surgery. A comprehensive validated questionnaire was used. Handling of the intercostobrachial nerve was registered by the surgeon. Factors known by the first 3 weeks after surgery were modeled in ordinal logistic regression analyses. Five hundred thirty-seven patients with baseline data were included, and 475 (88%) were available for analysis at 1 year. At 1-year follow-up, the prevalence of moderate-to-severe pain at rest was 14% and during movement was 7%. Factors associated with pain at rest were age <65 years (odds ratio [OR]: 1.8, P = 0.02), breast conserving surgery (OR: 2.0, P = 0.006), axillary lymph node dissection with preservation of the intercostobrachial nerve (OR: 3.1, P = 0.0005), moderate-to-severe preoperative pain (OR: 5.7, P = 0.0002), acute postoperative pain (OR: 2.8, P = 0.0018), and signs of neuropathic pain at 1 week (OR: 2.1, P = 0.01). Higher preoperative diastolic blood pressure was associated with reduced risk of PPBCS (OR: 0.98 per mm Hg, P = 0.01). Both patient- and treatment-related risk factors predicted PPBCS. Identifying patients at risk may facilitate targeted intervention.
190 citations
TL;DR: This hypothesis posits that the precision with which multisensory information about the painful event is encoded and represented in the brain will determine the degree to which the painful response will subsequently generalize to similar events.
Abstract: It seemsthat despite extensive advances in multiple fields,we have made little ground. In this topical review, we put forwardanewhypothesisofchronicpainthatexplainsthemostcommonpainful disorders, such as chronic widespread pain, nonspecificback or neck pain, and fibromyalgia. Our hypothesis draws onalonghistoryoffundamentalresearchinassociativelearningandis based on 2 core assumptions (1) that pain can be considereda response, not just a stimulus, and (2) that encoding non-nociceptive information predictably coincident with nociceptiveinput underpins the response to subsequent similar events.Briefly, our hypothesis posits that the precision with whichmultisensoryinformation(temporal,proprioceptive,spatial)aboutthe painful event is encoded and represented in the brain willdetermine the degree to which the painful response willsubsequently generalize to similar events.Much of the literature on pain considers it analogous tonociception, activity in high-threshold afferent neurons and theircentral projections. However, a very large body of evidencedemonstrates that nociception is neither sufficient nor necessaryfor pain (see Refs. 4,11,22). Pain is now considered a consciousexperiencethatcanbe,andoftenis,associatedwithnociception,but it is always modulated by a myriad of neurobiological,environmental, and cognitive factors. Plasticity, or the alterationsin stimulus–response patterns that occur over time, is thought tobeimportantinchronicpainandcanoccurinatleast2ways.Oneis nonassociative when the organism’s response to a stimuluschanges by virtue of repeated exposure to that particularstimulus. Habituation is 1 example of nonassociative plasticity,such that the response to a given stimulus decreases.Sensitization is another example, such that the response toa given stimulus increases. Sensitization of spinal nociceptors isconsidered a key mechanism underpinning persistent pain afterprimary nerve trauma or dysfunction; repeated noxious stimula-tion leads to a shift in the stimulus–response pattern of the spinalnociceptor.Asecondarguablymorecomplexformofplasticityinvolvestheassociation of at least 2 stimuli, such is the typical case ofclassical (Pavlovian) conditioning or associative learning.
185 citations
TL;DR: Improving the current way of conducting clinical trials in NP could contribute to reduce therapeutic failures and may have an impact on future therapeutic algorithms.
Abstract: Neuropathic pain (NP) is a significant medical and socioeconomic burden Epidemiological surveys have indicated that many patients with NP do not receive appropriate treatment for their pain A number of pharmacological agents have been found to be effective in NP on the basis of randomized controlled trials including, in particular, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitor antidepressants, pregabalin, gabapentin, opioids, lidocaine patches, and capsaicin high-concentration patches Evidence-based recommendations for the pharmacotherapy of NP have recently been updated However, meta-analyses indicate that only a minority of patients with NP have an adequate response to drug therapy Several reasons may account for these findings, including a modest efficacy of the active drugs, a high placebo response, the heterogeneity of diagnostic criteria for NP, and an inadequate classification of patients in clinical trials Improving the current way of conducting clinical trials in NP could contribute to reduce therapeutic failures and may have an impact on future therapeutic algorithms
TL;DR: It is demonstrated, that some analgesic interventions may have the capacity to reduce mean opioid requirements and/or mean pain intensity compared with controls, but the available randomized placebo-controlled trials does not allow a designation of a “best proven intervention” for THA.
Abstract: Treatment of postoperative pain should rely on results from randomized controlled trials and meta-analyses of high scientific quality. The efficacy of a particular intervention may depend on the type of surgical procedure, which supports the reporting of "procedure-specific" interventions. The aim of this systematic review was to document the procedure-specific evidence for analgesic interventions after total hip arthroplasty (THA). This PRISMA-compliant and PROSPERO-registered review includes randomized placebo-controlled trials (RCTs) of medication-based analgesic interventions after THA. Endpoints were postoperative opioid consumption, pain scores (rest and during mobilization), adverse events, and length of hospital stay. Fifty-eight trials with 19 different interventions were retrieved. High risk of bias, substantial differences in assessment-tools and criteria for pain, irregular reporting of adverse events, considerable differences in supplemental analgesic consumption, and basic analgesic regimens generally characterized trials. Meta-analyses of non-steroidal anti-inflammatory drugs, local infiltration analgesia, intrathecal opioids, and lumbar plexus block provided a 24-hour intravenous morphine-sparing effect of 14.1 (95 % confidence interval: 8.0-20.2) mg, 7.5 (3.7-11.3) mg, 19.8 (14.9-24.7) mg, and 11.9 (6.4-17.3) mg, respectively. Non-steroidal anti-inflammatory drugs and lumbar plexus block were demonstrated to provide reductions in postoperative pain scores. Intrathecal opioids increased pruritus, and lumbar plexus block reduced nausea and pruritus. The GRADE-rated quality of evidence ranged from low to very low throughout the analyses. This review demonstrated, that some analgesic interventions may have the capacity to reduce mean opioid requirements and/or mean pain intensity compared with controls, but the available randomized placebo-controlled trials does not allow a designation of a "best proven intervention" for THA.
TL;DR: A novel intracellular pathway, the IL-6/JAK/PI3K/TRPV1 signaling cascade, is disclosed, which may underlie the development of peripheral sensitization and bone cancer–induced pain.
Abstract: Primary and metastatic cancers that affect bone are frequently associated with severe and intractable pain. The mechanisms underlying the pathogenesis of bone cancer pain still remain largely unknown. Previously, we have reported that sensitization of primary sensory dorsal root ganglion (DRG) neurons contributes to the pathogenesis of bone cancer pain in rats. In addition, numerous preclinical and clinical studies have revealed the pathological roles of interleukin-6 (IL-6) in inflammatory and neuropathic hyperalgesia. In this study, we investigated the role and the underlying mechanisms of IL-6 in the development of bone cancer pain using in vitro and in vivo approaches. We first demonstrated that elevated IL-6 in DRG neurons plays a vital role in the development of nociceptor sensitization and bone cancer-induced pain in a rat model through IL-6/soluble IL-6 receptor (sIL-6R) trans-signaling. Moreover, we revealed that functional upregulation of transient receptor potential vanilloid channel type 1 (TRPV1) in DRG neurons through the activation of Janus kinase (JAK)/phosphatidylinositol 3-kinase (PI3K) signaling pathway contributes to the effects of IL-6 on the pathogenesis of bone cancer pain. Therefore, suppression of functional upregulation of TRPV1 in DRG neurons by the inhibition of JAK/PI3K pathway, either before surgery or after surgery, reduces the hyperexcitability of DRG neurons and pain hyperalgesia in bone cancer rats. We here disclose a novel intracellular pathway, the IL-6/JAK/PI3K/TRPV1 signaling cascade, which may underlie the development of peripheral sensitization and bone cancer-induced pain.
TL;DR: It is confirmed that interictal CGRP levels can be of help in predicting the response to onabotA and suggested that the mechanism of action of onabOTA in CM is the reversal of sensitization as a result of the inhibition of CGRp release.
Abstract: OnabotulinumtoxinA (onabotA) has shown efficacy in chronic migraine (CM). Its mechanism of action, however, remains obscure. We have analysed whether treatment with onabotA is able to induce changes in interictal plasma calcitonin gene-related peptide (CGRP) concentrations, which have been shown to be increased in patients with CM. Calcitonin gene-related peptide levels were determined in samples obtained from the right antecubital vein using ELISA, outside a migraine attack and having taken no symptomatic medication in the previous 24 hours, in 83 patients with CM (average age 44 years; 94% females) before and 1 month after treatment with 155 to 195 U of onabotA. CGRP levels after onabotA treatment (median, 51.89 pg/mL; range, 199.4-10.2) were significantly lower as compared with CGRP levels obtained before onabotA treatment (median, 74.09 pg/mL; range, 241.0-11.4; P = 0.001). Pretreatment CGRP levels in responders (76.85 pg/mL) were significantly higher than those seen in nonresponders (50.45 pg/mL; P = 0.001). One month after treatment, the CGRP levels did not change in nonresponders (51.89 pg/mL; P not significant), but significantly decreased in responders (52.48 pg/mL; P = 0.003). A number of demographic factors, clinical features, and comorbidities were not different in responders as compared with those of nonresponders. These results confirm that interictal CGRP levels can be of help in predicting the response to onabotA and suggest that the mechanism of action of onabotA in CM is the reversal of sensitization as a result of the inhibition of CGRP release.
TL;DR: The results of the present study highlight the very significant public health potential of carefully designed and administered internet-delivered pain management programs and indicate that these programs can be successfully administered with several levels of clinical support.
Abstract: The present study evaluated an internet-delivered pain management program, the Pain Course, when provided with different levels of clinician support. Participants (n = 490) were randomised to 1 of 4 groups: (1) Regular Contact (n = 143), (2) Optional Contact (n = 141), (3) No Contact (n = 131), and (4) a treatment-as-usual Waitlist Control Group (n = 75). The treatment program was based on the principles of cognitive behaviour therapy and comprised 5 internet-delivered lessons provided over 8 weeks. The 3 Treatment Groups reported significant improvements (between-group Cohen's d; avg. reduction) in disability (ds ≥ 0.50; avg. reduction ≥ 18%), anxiety (ds ≥ 0.44; avg. reduction ≥ 32%), depression (ds ≥ 0.73; avg. reduction ≥ 36%), and average pain (ds ≥ 0.30; avg. reduction ≥ 12%) immediately posttreatment, which were sustained at or further improved to 3-month follow-up. High treatment completion rates and levels of satisfaction were reported, and no marked or consistent differences were observed between the Treatment Groups. The mean clinician time per participant was 67.69 minutes (SD = 33.50), 12.85 minutes (SD = 24.61), and 5.44 minutes (SD = 12.38) for those receiving regular contact, the option of contact, and no clinical contact, respectively. These results highlight the very significant public health potential of carefully designed and administered internet-delivered pain management programs and indicate that these programs can be successfully administered with several levels of clinical support.
TL;DR: In this article, the authors investigated the prevalence of pain in people with dementia admitted to general hospitals and explore the association between pain and behavioural and psychiatric symptoms of dementia (BPSD).
Abstract: Pain is underdetected and undertreated in people with dementia. We aimed to investigate the prevalence of pain in people with dementia admitted to general hospitals and explore the association between pain and behavioural and psychiatric symptoms of dementia (BPSD). We conducted a longitudinal cohort study of 230 people, aged above 70, with dementia and unplanned medical admissions to 2 UK hospitals. Participants were assessed at baseline and every 4 days for self-reported pain (yes/no question and FACES scale) and observed pain (Pain Assessment in Advanced Dementia scale [PAINAD]) at movement and at rest, for agitation (Cohen-Mansfield Agitating Inventory [CMAI]) and BPSD (Behavioural Pathology in Alzheimer Disease Scale [BEHAVE-AD]). On admission, 27% of participants self-reported pain rising to 39% on at least 1 occasion during admission. Half of them were able to complete the FACES scale, this proportion decreasing with more severe dementia. Using the PAINAD, 19% had pain at rest and 57% had pain on movement on at least 1 occasion (in 16%, this was persistent throughout the admission). In controlled analyses, pain was not associated with CMAI scores but was strongly associated with total BEHAVE-AD scores, both when pain was assessed on movement (β = 0.20, 95% confidence interval [CI] = 0.07-0.32, P = 0.002) and at rest (β = 0.41, 95% CI = 0.14-0.69, P = 0.003). The association was the strongest for aggression and anxiety. Pain was common in people with dementia admitted to the acute hospital and associated with BPSD. Improved pain management may reduce distressing behaviours and improve the quality of hospital care for people with dementia.
TL;DR: It is suggested that pharmacological strategies through manipulation of the monoamine system could be used to enhance DNIC in patients by blocking descending facilitations with ondansetron or enhancing norepinephrine inhibitions, so possibly reducing chronic pain.
Abstract: Diffuse noxious inhibitory controls (DNICs) utilize descending inhibitory controls through poorly understood brain stem pathways. The human counterpart, conditioned pain modulation, is reduced in patients with neuropathy aligned with animal data showing a loss of descending inhibitory noradr
TL;DR: Pregabalin analgesic effectiveness is largely restricted to surgical procedures associated with pronociceptive mechanisms and the clinical significance of observed pregabalin benefits must be weighed against the uncertainties about serious harms and enhanced recovery to inform the careful selection of surgical patients.
Abstract: Evidence supporting postoperative pain management using pregabalin as an adjunct intervention across various surgical pain models is lacking. The objective of this systematic review was to evaluate "model-specific" comparative effectiveness and harms of pregabalin following a previously published systematic review protocol. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through August 2013. Data were screened and single extraction with independent verification and dual risk of bias assessment was performed. Quality of evidence (QoE) was rated using the GRADE approach. Primary outcomes were pain relief at rest and on movement and reduction in postoperative analgesic consumption. A total of 1423 records were screened, and 43 studies were included. Perioperative pregabalin resulted in: 16% (95% confidence interval [CI], 9%-21%) reduction in analgesic consumption (moderate QoE, 24 trials) and a small reduction in the magnitude of pain in surgeries associated with pronociceptive pain. Per 1000 patients, 10 more will experience blurred vision (95% CI, 5-20 more; moderate QoE, 17 trials) and 41 more sedation (95% CI, 13-77 more, 17 trials). To prevent 1 case of perioperative nausea and vomiting, the number needed to treat is 11 (95% CI: 7-28, 25 trials). Inadequate evidence addressed outcomes of enhanced recovery and serious harms. Pregabalin analgesic effectiveness is largely restricted to surgical procedures associated with pronociceptive mechanisms. The clinical significance of observed pregabalin benefits must be weighed against the uncertainties about serious harms and enhanced recovery to inform the careful selection of surgical patients. Recommendations for future research are proposed.
TL;DR: In this article, a workshop was held to solicit advice from experts in transcranial magnetic stimulation (TMS), pain research, and clinical trials, and the authors recommended that researchers standardize and document all TMS parameters and improve strategies for sham and double blinding.
Abstract: Recognizing that electrically stimulating the motor cortex could relieve chronic pain sparked development of noninvasive technologies. In transcranial magnetic stimulation (TMS), electromagnetic coils held against the scalp influence underlying cortical firing. Multiday repetitive transcranial magnetic stimulation (rTMS) can induce long-lasting, potentially therapeutic brain plasticity. Nearby ferromagnetic or electronic implants are contraindications. Adverse effects are minimal, primarily headaches. Single provoked seizures are very rare. Transcranial magnetic stimulation devices are marketed for depression and migraine in the United States and for various indications elsewhere. Although multiple studies report that high-frequency rTMS of the motor cortex reduces neuropathic pain, their quality has been insufficient to support Food and Drug Administration application. Harvard's Radcliffe Institute therefore sponsored a workshop to solicit advice from experts in TMS, pain research, and clinical trials. They recommended that researchers standardize and document all TMS parameters and improve strategies for sham and double blinding. Subjects should have common well-characterized pain conditions amenable to motor cortex rTMS and studies should be adequately powered. They recommended standardized assessment tools (eg, NIH's PROMIS) plus validated condition-specific instruments and consensus-recommended metrics (eg, IMMPACT). Outcomes should include pain intensity and qualities, patient and clinician impression of change, and proportions achieving 30% and 50% pain relief. Secondary outcomes could include function, mood, sleep, and/or quality of life. Minimum required elements include sample sources, sizes, and demographics, recruitment methods, inclusion and exclusion criteria, baseline and posttreatment means and SD, adverse effects, safety concerns, discontinuations, and medication-usage records. Outcomes should be monitored for at least 3 months after initiation with prespecified statistical analyses. Multigroup collaborations or registry studies may be needed for pivotal trials.
TL;DR: It is suggested that although preoperative widespread pressure pain sensitivity is associated with pain severity before and after joint replacement, it is not a predictor of the amount of pain relief that patients gain from joint replacement surgery, independent of preoperative pain severity.
Abstract: Chronic pain after joint replacement is common, affecting approximately 10% of patients after total hip replacement (THR) and 20% of patients after total knee replacement (TKR). Heightened generalized sensitivity to nociceptive input could be a risk factor for the development of this pain. The primary aim of this study was to investigate whether preoperative widespread pain sensitivity was associated with chronic pain after joint replacement. Data were analyzed from 254 patients receiving THR and 239 patients receiving TKR. Pain was assessed preoperatively and at 12 months after surgery using the Western Ontario and McMaster Universities Osteoarthritis Pain Scale. Preoperative widespread pain sensitivity was assessed through measurement of pressure pain thresholds (PPTs) at the forearm using an algometer. Statistical analysis was conducted using linear regression and linear mixed models, and adjustments were made for confounding variables. In both the THR and TKR cohort, lower PPTs (heightened widespread pain sensitivity) were significantly associated with higher preoperative pain severity. Lower PPTs were also significantly associated with higher pain severity at 12 months after surgery in the THR cohort. However, PPTs were not associated with the change in pain severity from preoperative to 12 months postoperative in either the TKR or THR cohort. These findings suggest that although preoperative widespread pressure pain sensitivity is associated with pain severity before and after joint replacement, it is not a predictor of the amount of pain relief that patients gain from joint replacement surgery, independent of preoperative pain severity.
TL;DR: The proposed Threat Interpretation Model suggests a relationship between threat, interpretation, and stimuli in determining attentional processes, which while tentative generates important testable predictions regarding the role of attention in pain and builds on previous theoretical and empirical work in this area.
Abstract: Individuals with chronic pain demonstrate attentional biases towards pain-related stimuli. However, the clinical importance of these biases is yet to be determined and a sound theoretical model for explaining the role of attentional biases in the development and maintenance of pain is lacking. Within this article, we (1) systematically review prospective and experimental research exploring attentional biases and pain outcomes in light of current theoretical models and (2) propose a theoretical framework for understanding attention bias in pain. Across prospective research, an attentional pattern of vigilance-avoidance was observed. Interventions targeting attentional biases were less consistent; however, there were promising findings amongst studies that found attentional training effects, particularly for laboratory research. The proposed Threat Interpretation Model suggests a relationship between threat, interpretation and stimuli in determining attentional processes, which whilst tentative generates important testable predictions regarding the role of attention in pain, and builds upon previous theoretical and empirical work in this area.
TL;DR: This paper highlights studies examining the effects of validation of pain-related thoughts and feelings and highlights several important future directions for research on the influence of validation on chronic pain.
Abstract: There is growing recognition that pain communication is important, and the way that people (e.g. partners, healthcare providers) respond to patients sharing their pain-related thoughts and feelings may have significant implications for pain-related outcomes[8]. One potentially important factor that has been relatively understudied until recently is the level of validation that may or may not be provided by people who are the recipients of a pain communication [4].
Many patients with chronic pain believe that others do not understand their pain or even consider their pain condition to be legitimate[9], beliefs which are likely to lead to increases in psychological distress and negative affect. It is possible that validation of pain-related thoughts and feelings for these patients may lead to reductions in negative affect. Furthermore, validation from a romantic partner may enhance relationship intimacy, which is related to several positive benefits (e.g. increased positive affect, improved psychological well-being) [10; 11]. Despite the potential benefits of validation, some research suggests that receiving social reinforcement (including validation) after sharing pain-related thoughts and feelings may be associated with worse patient outcomes such as increased pain[22].
This paper highlights studies examining the effects of validation of pain-related thoughts and feelings. It is divided into four sections. In the first section, we describe the concept of validation. The second section describes several theories that attempt to explain the impact of validation on patient outcomes (e.g. affect, report of pain intensity). In the third section, we review a number of studies examining validation and invalidation in the context of pain. In the final section of the paper, we highlight several important future directions for research on the influence of validation on chronic pain.
TL;DR: The findings support the theory that CRPS represents an aberrant protective response to perceived threat of tissue injury and could be considered as target variables for early treatment.
Abstract: Previous studies have shown that the outcomes of complex regional pain syndrome (CRPS) vary significantly between patients, but few studies have identified prognostic indicators. The aim of this study was to determine whether psychological factors are associated with recovery from recently onset CRPS amongst patients followed prospectively for 1 year. Sixty-six patients with CRPS (type 1) were recruited within 12 weeks of symptom onset and assessed immediately and at 6 and 12 months, during which time they received treatment as usual. At each assessment, the following were measured: signs and symptoms of CRPS, pain, disability, depression, anxiety, stress, pain-related fear, pain catastrophising, laterality task performance, body perception disturbance, and perceived ownership of the limb. Mixed-effects models for repeated measures were conducted to identify baseline variables associated with CRPS severity, pain, and disability over the 12 months. Results showed that scores for all 3 outcome variables improved over the study period. Males and those with lower levels of baseline pain and disability experienced the lowest CRPS severity scores over 12 months. Those with lower baseline anxiety and disability had the lowest pain intensity over the study period, and those with lower baseline pain and pain-related fear experienced the least disability over the 12 months. This suggests that anxiety, pain-related fear, and disability are associated with poorer outcomes in CRPS and could be considered as target variables for early treatment. The findings support the theory that CRPS represents an aberrant protective response to perceived threat of tissue injury.
TL;DR: The results suggest that as in the rat, most lamina I ALT projection neurons in the lumbar enlargement can be retrogradely labelled from the lateral parabrachial area, and that the majority of these cells express the neurokinin 1 receptor (NK1r), and that these are larger than other NK1r-expressing neurons in this lamina.
Abstract: The anterolateral tract (ALT), which originates from neurons in lamina I and the deep dorsal horn, represents a major ascending output through which nociceptive information is transmitted to brain areas involved in pain perception. Although there is detailed quantitative information concerning the ALT in the rat, much less is known about this system in the mouse, which is increasingly being used for studies of spinal pain mechanisms because of the availability of genetically modified lines. The aim of this study was therefore to determine the extent to which information about the ALT in the rat can be extrapolated to the mouse. Our results suggest that as in the rat, most lamina I ALT projection neurons in the lumbar enlargement can be retrogradely labelled from the lateral parabrachial area, that the majority of these cells (∼ 90%) express the neurokinin 1 receptor (NK1r), and that these are larger than other NK1r-expressing neurons in this lamina. This means that many lamina I spinoparabrachial cells can be identified in NK1r-immunostained sections from animals that have not received retrograde tracer injections. However, we also observed certain species differences, in particular we found that many spinoparabrachial cells in laminae III and IV lack the NK1r, meaning that they cannot be identified based solely on the expression of this receptor. We also provide evidence that the majority of spinoparabrachial cells are glutamatergic and that some express substance P. These findings will be important for studies designed to unravel the complex neuronal circuitry that underlies spinal pain processing.
TL;DR: Decreased pain sensitivity seems to be an endophenotype of schizophrenia spectrum disorders, and how this alteration links to other dimensions of schizophrenia and physical comorbidity-related help-seeking behaviour/morbidity/mortality requires further study.
Abstract: Patients with schizophrenia report reduced pain sensitivity in clinical studies, but experimental studies are required to establish pain sensitivity as a potential endophenotype. We conducted a systematic review of electronic databases from database inception until April 15, 2015, including experimental studies investigating pain among patients with schizophrenia spectrum disorder vs healthy controls. A random-effect meta-analysis yielding Hedges' g ±95% confidence intervals (CIs) as the effect size (ES) measure was conducted. Primary outcome was a pooled composite of pain threshold and pain tolerance; secondary outcomes included these parameters individually, plus sensory threshold, physiological pain response, and pain intensity or unpleasantness. Across 17 studies, patients with schizophrenia spectrum disorder (n = 387; age, 30.7 ± 6.9 years; females, 31.9%; illness duration, 7.0 ± 5.7 years) were compared with controls (n = 483; age, 29.5 ± 7.4 years; females, 31.0%). Patients had elevated pain threshold/pain tolerance vs controls (ES = 0.583; 95% CI, 0.212-0.954; P = 0.002; studies = 15). Results were similar in antipsychotic-free individuals (ES = 0.599; 95% CI, 0.291-0.907; P < 0.0001; studies = 8), with trend-level significance in antipsychotic-treated individuals (ES = 0.566; 95% CI, -0.007 to 1.125; P = 0.047; studies = 9). Likewise, patients with schizophrenia had increased pain tolerance (ES = 0.566; 95% CI, 0.235-0.897; P = 0.0001; studies = 6), sensory threshold (ES = 1.16; 95% CI, 0.505-1.727; P < 0.0001; studies = 5), and pain threshold (ES = 0.696; 95% CI, 0.407-0.986; P < 0.001; studies = 9), as well as reduced physiological response to noxious stimuli (ES = 0.456; 95% CI, 0.131-0.783; P = 0.006) and pain intensity/unpleasantness ratings (ES = 0.547; 95% CI, 0.146-0.949; P = 0.008). Findings were similarly significant in antipsychotic-free patients with schizophrenia (analysable parameters = 4) and antipsychotic-treated individuals (analysable parameters = 2). Finally, greater psychiatric symptoms moderated increased pain threshold, and younger patient age moderated increased pain tolerance. Decreased pain sensitivity seems to be an endophenotype of schizophrenia spectrum disorders. How this alteration links to other dimensions of schizophrenia and physical comorbidity-related help-seeking behaviour/morbidity/mortality requires further study.
TL;DR: These experiments suggest that rodents are capable of producing simplified versions of any number of social phenomena involving empathy, previously thought to be the sole province of human beings.
Abstract: The social domain of the biopsychosocial model of pain has been greatly understudied compared with the biological and psychological domains but holds great promise for furthering our understanding, and better treatment, of pain. Recent years have seen an explosion of interest in social neuroscience and have revealed the ability of pain stimuli to alter social interactions. These experiments suggest that rodents are capable of producing simplified versions of any number of social phenomena involving empathy, previously thought to be the sole province of human beings. This review describes the state of science in both humans and nonhuman animals, and notes intriguing parallels in observations from both species. Indeed, my laboratory is starting to demonstrate perfectly translatable findings regarding social modulation of pain in rodents and humans.
TL;DR: It is found that the people who have been prescribed strong opioids for chronic pain have very complex demographic and clinical profiles and major age-related differences in the experiences of pain, coping, mental health, and substance use suggest the necessity of differential approaches to treatment.
Abstract: There has been a recent increase in public and professional concern about the prescription of strong prescription opioids for pain Despite this concern, research to date has been limited because of a number of factors such as small sample sizes, exclusion of people with complex comorbidities, and studies of short duration The Pain and Opioids IN Treatment is a 2-year prospective cohort study of 1500 people prescribed with pharmaceutical opioids for their chronic pain This article provides an overview of the demographic and clinical characteristics of the cohort using the baseline data of 1514 community-based people across Australia Participants had been in pain for a period of 10 years and had been on prescription opioids for approximately 4 years One in 10 was on a daily morphine equivalent dose of ≥200 mg Employment and income levels were low, and two-thirds of the sample reported that their pain had impacted on their employment status Approximately 50% screened positive for current moderate-to-severe depression, and 1 in 5 had made a lifetime suicide attempt There were a number of age-related differences The younger groups experienced higher levels of pain and pain interference, more mental health and substance use issues, and barriers to treatment, compared with the older group This study found that the people who have been prescribed strong opioids for chronic pain have very complex demographic and clinical profiles Major age-related differences in the experiences of pain, coping, mental health, and substance use suggest the necessity of differential approaches to treatment
TL;DR: A growing number of brain imaging studies in irritable bowel syndrome, functional dyspepsia, and bladder pain syndrome/interstitial cystitis has identified abnormalities in evoked brain responses, resting state activity, and connectivity, as well as in gray and white matter properties.
Abstract: Chronic visceral pain syndromes are important clinical problems with largely unmet medical needs. Based on the common overlap with other chronic disorders of visceral or somatic pain, mood and affect, and their responsiveness to centrally targeted treatments, an important role of central nervous system in their pathophysiology is likely. A growing number of brain imaging studies in irritable bowel syndrome, functional dyspepsia and bladder pain syndrome/interstitial cystitis has identified abnormalities in evoked brain responses, resting state activity and connectivity, as well as in grey and white matter properties. Structural and functional alterations in brain regions of the salience, emotional arousal, and sensorimotor networks, as well as in prefrontal regions, are the most consistently reported findings. Some of these changes show moderate correlations with behavioral and clinical measures. Most recently, data driven machine-learning approaches to larger data sets have been able to classify visceral pain syndromes from healthy control subjects. Future studies need to identify the mechanisms underlying the altered brain signatures of chronic visceral pain and identify targets for therapeutic interventions.
TL;DR: This study determined the diameter of small unmyelinated nerve fibers by measuring ten transversely cut axons of each biopsy and confirmed previous findings of disturbed small fiber function in quantitative sensory testing and of reduced intraepidermal nerve fiber density in patients with fibromyalgia.
Abstract: Recent studies have provided evidence of pathology and functional abnormalities of small nerve fibers as a potential correlate of pain in the fibromyalgia syndrome. Here, we aimed to quantify dermal unmyelinated nerve fiber diameter at the electron microscopic level to find a potential morph
TL;DR: Lidocaine 5% patch had an effect on peripheral neuropathic pain, and it may be most efficacious in patients with IN phenotype, although the lack of significant phenotype differences may be caused by too low statistical power.
Abstract: In neuropathic pain with irritable nociceptor (IN) phenotype, upregulation of sodium channels on nociceptors is supposed to be an important pain mechanism that may be targeted by topical sodium channel blockade. This randomised, double-blind, phenotype panel, crossover study with 4-week treatment periods of lidocaine 5% patch and placebo was performed to search for phenotype differences in effect. The primary efficacy measure was the total pain intensity on an 11-point numeric rating scale, and the primary objective was to compare the effect of lidocaine in patients with and without IN phenotype as defined by hypersensitivity and preserved small-fibre function determined by quantitative sensory testing. Forty-six patients with neuropathic pain due to nerve injury or postherpetic neuralgia were randomised. The modified intention-to-treat population comprised 15 patients with irritable nociceptor and 25 patients with nonirritable nociceptor. In the total sample, lidocaine reduced pain by 0.3 numeric rating scale points (95% confidence interval [CI]: 0.1-0.5) and pain-related sleep disturbance by 0.6 points (95% CI: 0.4-0.8) more than placebo (P = 0.007 and P < 0.001) and relieved pain by 0.4 verbal score (-1-5) points more (P = 0.036). For these measures, there was no significant interaction between treatment and phenotype, but there was a significant interaction for pain paroxysms (0.8, 95% CI: 0.4-1.2, P < 0.001) and deep aching pain (0.6, 95% CI: 0.1-1.0, P = 0.013). In conclusion, lidocaine 5% patch had an effect on peripheral neuropathic pain, and it may be most efficacious in patients with IN phenotype. The lack of significant phenotype differences may be caused by too low statistical power.