An overview of offset analgesia and the comparison with conditioned pain modulation : a systematic literature review

Background: Offset analgesia (OA) is an increasingly described phenomenon to measure endogenous pain inhibition, in which a greater decrease in pain intensity is experienced than would be predicted by the decrease in painful stimulation. The temporal filtering in this OA phenomenon differs from the spatial filtering in the commonly described conditioned pain modulation (CPM). Yet, the knowledge on the efficacy of OA in chronic pain patients is scarce, compared to CPM efficacy. Objective: This systematic review has been conducted to provide an overview of the current knowledge regarding OA, and to compare it to CPM. Study Design: A systematic review of research studies that investigated the application or mechanisms of OA. Setting: The present study took place at Ghent University and the University of Antwerp. Methods: This systematic review follows the PRISMA guidelines. The electronic databases Pubmed and Web of Science were searched in January 2015. Full text clinical reports addressing OA were included. The checklists for randomized controlled trials, case-control studies, and cohort-studies provided by the Dutch Institute for Healthcare Improvement and the Dutch Cochrane Centre were used to assess methodological quality. The articles received a level of evidence A1, A2, B, C, or D, based on study design and risk of bias. These levels were used to determine the strength of conclusion (level 1 to 4). Results: Seventeen articles met the inclusion criteria. Sixteen studies used quantitative sensory testing to provoke OA; however, differences in protocols are present. OA can function as a non-opioid mediated assessment tool for endogenous pain inhibition, and activates brain regions such as periaqueductal gray (PAG), dorsolateral prefontral cortex, insula, medulla, pons and cerebellum, indicating strong brain derived pain modulation. The primary somatosensory cortex is, conversely, less activated during OA. OA is decreased in neuropathic patients. Nonetheless, evidence for the influence of individual factors on OA is limited. OA and CPM seem to rely on different mechanisms. Limitations: Search strategy was taken wide, wherefore a large variety of research perspectives were included. Conclusions: This systematic review displays OA as a temporal filtering mechanisms that is more brain-derived compared to the spatial assessment method CPM. There is strong evidence for reduced OA in neuropathic patients, however, evidence regarding OA in (sub) acute and central sensitization patients, and the influence of personal factors on OA is currently scarce and needs further investigation

Inventory of personal factors influencing conditioned pain modulation in healthy people: a systematic literature review

Background: Conditioned pain modulation (CPM) is believed to play an important role in the development and exacerbation of chronic pain, because dysfunction of CPM is associated with a shift in balance between pain facilitation and pain inhibition. In many patients with central sensitization, CPM is less efficacious. Besides that, efficacy of CPM is highly variable in healthy people. Consequently, it seems that several individual variables may influence CPM. A systematic review examining personal factors influencing CPM was conducted. Methods: This systematic review follows the PRISMA guidelines. Pubmed and Web of Science were searched using different synonyms of CPM. Full-text clinical reports addressing the influence of personal factors on CPM in healthy adults were included. Checklists for RCTs and case-control studies provided by the Dutch Institute for Healthcare Improvement (CBO) and the Dutch Cochrane Centre were utilized to assess methodological quality. Levels of evidence and strength of conclusion were assigned using the CBO guidelines. Results: Forty-six articles were identified that reported the influence of personal factors on CPM. Quality assessment revealed 10 studies with a methodological quality less than 50% wherefore they were excluded (21.8%), resulting in a general total methodological quality score of 72.5%. Overall younger adult age, male gender, ovulatory phase, positive expectations, attention to the conditioning stimulus, and carrier of the 5-HTTLPR long allele result in better CPM. Conclusion: It is advised for future studies to take these factors into account. Further research regarding the influence of oral contraceptives, catastrophizing, information about conditioning stimulation, distraction, physical activity, and genetics on CPM magnitude is required

Small-scale eruptive filaments on the quiet sun

A study of a little known class of eruptive events on the quiet sun was conducted. All of 61 small-scale eruptive filamentary structures were identified in a systematic survey of 32 days of H alpha time-lapse films of the quiet sun acquired at Big Bear Solar Observatory. When fully developed, these structures have an average length of 15 arc seconds before eruption. They appear to be the small-scale analog of large-scale eruptive filaments observed against the disk. At the observed rate of 1.9 small-scale eruptive features per field of view per average 7.0 hour day, the rate of occurence of these events on the sun were estimated to be greater than 600 per 24 hour day.. The average duration of the eruptive phase was 26 minutes while the average lifetime from formation through eruption was 70 minutes. A majority of the small-scale filamentary sturctures were spatially related to cancelling magnetic features in line-of-sight photospheric magnetograms. Similar to large-scale filaments, the small-scale filamentary structures sometimes divided opposite polarity cancelling fragments but often had one or both ends terminating at a cancellation site. Their high numbers appear to reflect the much greater flux on the quiet sun. From their characteristics, evolution, and relationship to photospheric magnetic flux, it was concluded that the structures described are small-scale eruptive filaments and are a subset of all filaments

Central sensitization in urogynecological chronic pelvic pain : a systematic literature review

Background: Chronic pelvic pain (CPP) is a complex pain syndrome. Since its pathogenesis is still poorly understood and structural alterations in pain related brain regions may be present, there is a greater acceptance that sensitization of the central nervous system (CNS) plays an important role in the development and maintenance of chronicity. Objective: The purpose of this study is to systematically review the scientific evidence regarding central sensitization (CS) in female patients with urogynecological CPP. Study Design: Systematic review of the literature. Methods: A systematic literature search was conducted in PubMed and Web of Science using different keyword combinations related to urogynecological CPP and central sensitization. Full text clinical reports addressing CS in adult women with urogynecological CPP were included and assessed for methodological quality by 2 independent reviewers. Results: After screening for the eligibility, a total of 29 full-text articles with low to good methodological quality were retained. All studies were observational, 27 of which were case-control and 2 of which were cohorts. Sensitivity of the CNS was investigated by using a variety of methods. Although different central mechanisms seem to be involved in pain processing, the present evidence suggests hyperexcitability of the CNS in patients with urogynecological CPP. Altered brain morphology and function, generalized hyperalgesia to different type of stimuli, overactive bottom-up nociceptive mechanisms, and autonomic dysregulation were established in patients with urogynecological CPP. Nevertheless, diffuse noxious inhibitory control seemed normal, and therefore the contribution of an impaired endogenous pain inhibition mechanism to CPP requires further study. The same goes for the contribution of psychological factors. Limitations: The level of evidence of retained studies is low due to the observational study designs and a wide range of diagnoses and assessment methods. Conclusion: Although the majority of the literature provides evidence for the presence of CS in urogynecological CPP with changes in brain morphology/function and sensory function, it is unclear whether these changes in central pain processing are secondary or primary to CPP, especially since evidence regarding the function of endogenous pain inhibition and the role of psychosocial pain facilitation is scarce. Further studies with good methodological quality are needed in order to clarify exact mechanisms

Does acetaminophen activate endogenous pain inhibition in chronic fatigue syndrome/fibromyalgia and rheumatoid arthritis? : a double-blind randomized controlled cross-over trial

Background: Although enhanced temporal summation (TS) and conditioned pain modulation (CPM), as characteristic for central sensitization, has been proved to be impaired in different chronic pain populations, the exact nature is still unknown. Objectives: We examined differences in TS and CPM in 2 chronic pain populations, patients with both chronic fatigue syndrome (CFS) and comorbid fibromyalgia (FM) and patients with rheumatoid arthritis (RA), and in sedentary, healthy controls, and evaluated whether activation of serotonergic descending pathways by acetaminophen improves central pain processing. Study Design: Double-blind randomized controlled trial with cross-over design. Methods: Fifty-three women (19 CFS/FM patients, 16 RA patients, and 18 healthy women) were randomly allocated to the experimental group (1 g acetaminophen) or the placebo group (1 g dextrose). Participants underwent an assessment of endogenous pain inhibition, consisting of an evaluation of temporal summation with and without conditioned pain modulation (CPM). Seven days later groups were crossed-over. Patients and assessors were blinded for the allocation. Results: After intake of acetaminophen, pain thresholds increased slightly in CFS/FM patients, and decreased in the RA and the control group. Temporal summation was reduced in the 3 groups and CPM at the shoulder was better overall, however only statistically significant for the RA group. Healthy controls showed improved CPM for both finger and shoulder after acetaminophen, although not significant. Limitations: The influence of acetaminophen on pain processing is inconsistent, especially in the patient groups examined. Conclusion: This is the first study comparing the influence of acetaminophen on central pain processing in healthy controls and patients with CFS/FM and RA. It seems that CFS/ FM patients present more central pain processing abnormalities than RA patients, and that acetaminophen may have a limited positive effect on central pain inhibition, but other contributors have to be identified and evaluated

The result of acute induced psychosocial stress on pain sensitivity and modulation in healthy people

Background: Pain can be influenced by several factors, including stress. Stress can have various reactions on pain. These reactions are influenced by several internal factors such as gender, age, and experience with stress or pain. Objectives: To determine the effect of acute stress on mechanical hyperalgesia (with pressure pain thresholds [PPT]), endogenous pain facilitation (measured by temporal summation [TS]), and inhibition (measured by conditioned pain modulation [CPM]) in healthy people and to determine which factors are responsible for this stress result. Study Design: Pre-posttest design. Setting: Healthy volunteers from Belgium. Methods: One hundred and one healthy pain-free patients underwent a modified Trier Social Stress Test. Prior and following the stress manipulation, PPT, TS, and CPM efficacy were determined in the mm. trapezius and quadriceps and overall. Furthermore, possible explanatory factors, such as fear of pain, pain catastrophizing, pain hypervigilance, and daily activity levels, were assessed using questionnaires. Results: We found a significant stress result on widespread pain sensitivity, with an increase of PPT (P 0.05), and a decrease in CPM efficacy (P < 0.001). Factors associated with the stress result were age, previous surgery, attentional focus on the conditioning stimulus during CPM, fear of pain, and daily activity levels. Limitations: The efficacy of the stress manipulation was not examined, and the lack of a control group prevented to examine a real stress-effect. Furthermore, no physiologic parameters were measured as possibly influencing internal factors for the stress-result. Conclusions: The increase in PPT was not a clinically significant change, whereas the decrease in CPM was meaningful. None of the factors predicted the stress result in all experimental pain measurements, and the predictions that were observed only explained a small proportion of the observed effects

HIV and TB co-infection in the ART era: CD4 count distributions and TB case fatality in Cape Town

Background In Cape Town, the roll-out of antiretroviral therapy (ART) has increased over the last decade with an estimated coverage of 63% of HIV- positive patients in 2013. The influence of ART on the characteristics of the population of HIV-positive patients presenting to the primary care TB programme is unknown. In this study, we examined trends in CD4 count distribution, ART usage and treatment outcomes among HIV-positive TB patients in Cape Town from 2009 to 2013. Methods Data from the electronic TB register on all newly registered drug-sensitive TB patients ≥18 years were analyzed retrospectively. Descriptive statistics were used to compare baseline characteristics, the CD4 count distribution and TB treatment outcomes both by year of treatment and ART status at the start of TB treatment. Survival analyses were used to assess the change in mortality risk during TB treatment over time, stratified by ART status at start of TB treatment. Results 118,989 patients were treated over 5 years. HIV prevalence among TB patients decreased from 50.9% in 2009 to 49.0% in 2013. The absolute number of HIV-positive TB cases declined by 13.2% between 2010 and 2013. More patients entered the TB programme on ART in 2013 compared to 2009 (30.0% vs 9.9%). Among these, the CD4 count distribution showed a year by year shift to higher CD4 counts. In 2013, over 75% of ART-naïve TB patients still had a CD4 count < 350 cells/mm3. ART initiation among ART-naive patients increased from 37.0 to 77.7% and TB case fatality declined from 7.4 to 5.2% (p < 0.001). In multivariate analysis a decrease in TB mortality was most strongly associated with CD4 count (Adjusted HR 0.82 per increase of 50 cells/mm3, 95% CI: 0.81–0.83, p < 001) and the initiation of ART during TB treatment (Adjusted HR 0.39, 95% CI: 0.35–0.42, p < 0.001). Conclusion Comprehensive changes in the ART and TB treatment programmes resulted in incremental increases in ART coverage for HIV-positive TB patients and a subsequent decrease in TB case fatality due to increased ART uptake in HIV-positive ART-naïve patients. However TB still remained a major presenting opportunistic infection with the majority of cases occurring at low CD4 counts