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

Dysfunctional endogenous analgesia during exercise in patients with chronic pain : to exercise or not to exercise?

Background: Exercise is an effective treatment for various chronic pain disorders, including fibromyalgia, chronic neck pain, osteoarthritis, rheumatoid arthritis, and chronic low back pain. Although the clinical benefits of exercise therapy in these populations are well established (i.e. evidence based), it is currently unclear whether exercise has positive effects on the processes involved in chronic pain (e.g. central pain modulation). Objectives: Reviewing the available evidence addressing the effects of exercise on central pain modulation in patients with chronic pain. Methods: Narrative review. Results: Exercise activates endogenous analgesia in healthy individuals. The increased pain threshold following exercise is due to the release of endogenous opioids and activation of (supra)spinal nociceptive inhibitory mechanisms orchestrated by the brain. Exercise triggers the release of β-endorphins from the pituitary (peripherally) and the hypothalamus (centrally), which in turn enables analgesic effects by activating μ-opioid receptors peripherally and centrally, respectively. The hypothalamus, through its projections on the periaqueductal grey, has the capacity to activate descending nociceptive inhibitory mechanisms. However, several groups have shown dysfunctioning of endogenous analgesia in response to exercise in patients with chronic pain. Muscle contractions activate generalized endogenous analgesia in healthy, pain-free humans and patients with either osteoarthritis or rheumatoid arthritis, but result in increased generalised pain sensitivity in fibromyalgia patients. In patients having local muscular pain (e.g. shoulder myalgia), exercising non-painful muscles activates generalized endogenous analgesia. However, exercising painful muscles does not change pain sensitivity either in the exercising muscle or at distant locations. Limitations: The reviewed studies examined acute effects of exercise rather than long-term effects of exercise therapy. Conclusions: A dysfunctional response of patients with chronic pain and aberrations in central pain modulation to exercise has been shown, indicating that exercise therapy should be individually tailored with emphasis on prevention of symptom flares. The paper discusses the translation of these findings to rehabilitation practice together with future research avenues

Unravelling Impaired Hypoalgesia at Rest and in Response to Exercise in Patients with Chronic Whiplash-Associated Disorders:Effects of a Single Administration of Selective Serotonin Reuptake Inhibitor versus Selective Norepinephrine Reuptake Inhibitor

(1) Background: Noradrenaline and serotonin have modulatory roles in pain signaling and in exercise-induced hypoalgesia. Patients with chronic whiplash-associated disorders often show impaired exercise-induced hypoalgesia. Therefore, this study aimed to examine the isolated effect of activating serotonergic or noradrenergic descending pathways on hypoalgesia at rest and in response to exercise in patients with chronic WAD by using respectively a single dose of a selective serotonin reuptake inhibitor (SSRI) and a selective norepinephrine reuptake inhibitor (NRI). (2) Methods: Twenty-five people with chronic WAD participated in this double-blind randomized controlled crossover experiment. Serotonin and noradrenaline concentrations were modulated by the oral ingestion of a single dose of citalopram (i.e., SSRI) or atomoxetine (i.e., SNRI). Quantitative sensory testing (including pressure pain thresholds and conditioned pain modulation) was measured before and after exercise in combination with no medication (1), atomoxetine (2), or citalopram (3) at three different test days. (3) Results: Random-intercept linear mixed models analysis was used to analyze pain outcomes (i.e., pain at rest and exercise-induced hypoalgesia) before and after exercise over the three conditions in patients with chronic WAD. No differences in pain at rest were found between the three conditions before exercise. The effect of exercise on pain outcome measures was not influenced by medication intake. The occupational status of the participants had a significant influence on the effect of exercise and medication on pain outcomes (p &lt; 0.05). Patients working full-time had some positive effect of atomoxetine on pain facilitation (p &lt; 0.05). Unemployed patients had some negative effect of citalopram on pain tolerance and experienced exercise-induced hypoalgesia (p &lt; 0.05). (4) Conclusions: A single dose of citalopram or atomoxetine did not result in changes in hypoalgesia at rest and in response to exercise. These results do not support the use of SSRI or selective NRI to overcome impaired hypoalgesia at rest or in response to exercise in people with chronic WAD. Effect of exercise and medication on pain in patients with chronic WAD is influenced by the occupational status.</p

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

A horizon scan of emerging technologies for alien species citizen science

Citizen Science (CS) significantly contributes to the study and management of biological invasions. Technological developments such as social media, internet scraping, eDNA, apps, sensors, search engines and predictive analytics can foster projects and increase the reach of CS. The list of tech is long and their potential for alien species CS is unclear. To help research funders and project initiators we performed a horizon scan on the value of emerging technologies for alien species CS. A network of 44 experts from the COST Action Alien-CSI identified and assessed 39 technologies. Assessors rated their usefulness on a 5-point Likert scale with respect to their potential to attract new audiences, improve inclusivity, applicability in daily life, ability to increase engagement, provide feedback, improve data quality and gather new data. The results of the scoring were discussed at a consensus workshop. Consistency among ratings was explored using inter-rater reliability metrics and ordination techniques. Experts were asked to explain and discuss the reasons for inconsistent rating across technologies or criteria, focusing on the evidence used or differences in interpretation of criteria. After this, one new round of individual re-evaluation of technologies followed. The discussions resulted in increased consensus on the potential of the different technologies. Mobile-based data collection platforms and social media (both their use to interact with CS participants as well as their potential for scraping new occurrence records) were the top-ranking technologies for IAS CS, followed by machine learning techniques, the application of AI and collective intelligence. Technologies differed considerably in their potential when different criteria were individually considered. For instance, DNA-based technologies ranked high on acquiring new data, open data technologies scored high on their potential to improve the quality of collected data. Virtual reality and gamification scored high on their potential to increase engagement in IAS CS

Gas Evolution as a Tool to study Reaction Kinetics under Biomimetic Conditions

The rational development of transition metal-based catalysts requires detailed kinetic analysis of catalytic reactions to aid catalyst design. Whereas kinetic data is relatively easy to obtain for catalysts used in synthetic applications, it is more challenging to study catalytic reactions for potential use in living systems, a rapidly growing field. In such applications, substantial concentrations of salts and biomolecules are present in the reaction medium, hampering the use of typically employed solution-phase analytical techniques. In this study, we explored the suitability of gas evolution as a probe to study kinetics under biomimetic conditions. As proof of concept, we demonstrate that the progress of two transition metal catalyzed bioorthogonal chemical reactions can be accurately monitored, regardless of the complexity of the medium. As such, we introduce a protocol to gain more insight into the performance of a catalytic system under biologically relevant conditions to progress iterative catalyst development for in vivo applications