Systemic Exercise-Induced Hypoalgesia Following Isometric Exercise Reduces Conditioned Pain Modulation

Objective Physically active individuals show greater conditioned pain modulation (CPM) compared with less active individuals. Understanding the effects of acute exercise on CPM may allow for a more targeted use of exercise in the management of pain. This study investigated the effects of acute isometric exercise on CPM. In addition, the between-session and within-session reliability of CPM was investigated. Design Experimental, randomized crossover study. Setting Laboratory at Marquette University. Subjects Thirty healthy adults (19.3±1.5 years, 15 males). Methods Subjects underwent CPM testing before and after isometric exercise (knee extension, 30% maximum voluntary contraction for three minutes) and quiet rest in two separate experimental sessions. Pressure pain thresholds (PPTs) at the quadriceps and upper trapezius muscles were assessed before, during, and after ice water immersions. Results PPTs increased during ice water immersion (i.e., CPM), and quadriceps PPT increased after exercise (P \u3c 0.05). CPM decreased similarly following exercise and quiet rest (P \u3e 0.05). CPM within-session reliability was fair to good (intraclass correlation coefficient [ICC] = 0.43–0.70), and the between-session reliability was poor (ICC = 0.20–0.35). Due to the variability in the systemic exercise-induced hypoalgesia (EIH) response, participants were divided into systemic EIH responders (N = 9) and nonresponders (N = 21). EIH responders experienced attenuated CPM following exercise (P = 0.03), whereas the nonresponders showed no significant change (P \u3e 0.05). Conclusions Isometric exercise decreased CPM in individuals who reported systemic EIH, suggesting activation of shared mechanisms between CPM and systemic EIH responses. These results may improve the understanding of increased pain after exercise in patients with chronic pain and potentially attenuated CPM

Changing the narrative in diagnosis and management of pain in the sacroiliac joint area

The sacroiliac joint (SIJ) is often considered to be involved when people present for care with low back pain where the sacroiliac joint (SIJ) is located. However, determining why the pain has arisen can be challenging, especially in the absence of a specific cause such as pregnancy, disease, or trauma, where the SIJ may be identified as a source of symptoms with the help of manual clinical tests. Nonspecific SIJ-related pain is commonly suggested to be causally associated with movement problems in the sacroiliac joint(s); a diagnosis traditionally derived from manual assessment of movements of the SIJ complex. Management choices often consist of patient education, manual treatment, and exercise. Although some elements of management are consistent with guidelines, this perspective argues that the assumptions on which these diagnoses and treatments are based are problematic, particularly if they reinforce unhelpful, pathoanatomical beliefs. This article reviews the evidence regarding the clinical detection and diagnosis of SIJ movement dysfunction. In particular, it questions the continued use of assessing movement dysfunction despite mounting evidence undermining the biological plausibility and subsequent treatment paradigms based on such diagnoses. Clinicians are encouraged to align their assessment methods and explanatory models to contemporary science to reduce the risk of their diagnoses and choice of intervention negatively affecting clinical outcome

IoMT-Driven eHealth: A Technological Innovation Proposal Based on Smart Speakers

Internet of Medical Things (IoMT) is a technological concept applied in healthcare contexts to achieve the digital interconnection of everyday objects with the Internet in order to make life easier for people. IoMT can help monitor, inform and notify not only caregivers, but provide healthcare providers with actual data to identify issues before they become critical or to allow for earlier invention. In this sense, this paper is contextualized in Assisted Repro duction Treatment (ART) processes to reduce the number of hospital visits, reduce healthcare costs and improve patientcare, as well as the productivity of the healthcare professional. So, we present an IoMT-based technological pro posal to manage and control the prescription of pharmacological treatments to patients who are carried out ART processes. In this context, we propose the integration of iMEDEA (modular system specialized in the management of electronic clinical records for ART unit) and smart speaker devices (specifically, Amazon’s Alexa), as well as the validation of our proposal in the real envi ronment offered by Inebir clinicMinisterio de Economía y Competitividad TIN2016-76956-C3-2-R (POLOLAS)Junta de Andalucía AT17-5904-US

Sensing of HSV-1 by the cGAS-STING pathway in microglia orchestrates antiviral defence in the CNS

Herpes simplex encephalitis (HSE) is the most common form of acute viral encephalitis in industrialized countries. Type I interferon (IFN) is important for control of herpes simplex virus (HSV-1) in the central nervous system (CNS). Here we show that microglia are the main source of HSV-induced type I IFN expression in CNS cells and these cytokines are induced in a cGAS-STING-dependent manner. Consistently, mice defective in cGAS or STING are highly susceptible to acute HSE. Although STING is redundant for cell-autonomous antiviral resistance in astrocytes and neurons, viral replication is strongly increased in neurons in STING-deficient mice. Interestingly, HSV-infected microglia confer STING-dependent antiviral activities in neurons and prime type I IFN production in astrocytes through the TLR3 pathway. Thus, sensing of HSV-1 infection in the CNS by microglia through the cGAS-STING pathway orchestrates an antiviral program that includes type I IFNs and immune-priming of other cell types

Fine-Tuning Roles of Endogenous Brain-Derived Neurotrophic Factor, TrkB and Sortilin in Colorectal Cancer Cell Survival

International audienceBACKGROUND: Neurotrophin receptors were initially identified in neural cells. They were recently detected in some cancers in association with invasiveness, but the function of these tyrosine kinase receptors was not previously investigated in colorectal cancer (CRC) cells. METHODS AND FINDINGS: We report herein that human CRC cell lines synthesize the neural growth factor Brain-derived neurotrophic factor (BDNF) under stress conditions (serum starvation). In parallel, CRC cells expressed high- (TrkB) and low-affinity (p75(NTR)) receptors at the plasma membrane, whereas TrkA and TrkC, two other high affinity receptors for NGF and NT-3, respectively, were undetectable. We demonstrate that BDNF induced cell proliferation and had an anti-apoptotic effect mediated through TrkB, as assessed by K252a, a Trk pharmacologic inhibitor. It suppressed both cell proliferation and survival of CRC cells that do not express TrkA nor TrkC. In parallel to the increase of BDNF secretion, sortilin, a protein acting as a neurotrophin transporter as well as a co-receptor for p75(NTR), was increased in the cytoplasm of primary and metastatic CRC cells, which suggests that sortilin could regulate neurotrophin transport in these cells. However, pro-BDNF, also detected in CRC cells, was co-expressed with p75(NTR) at the cell membrane and co-localized with sortilin. In contrast to BDNF, exogenous pro-BDNF induced CRC apoptosis, which suggests that a counterbalance mechanism is involved in the control of CRC cell survival, through sortilin as the co-receptor for p75(NTR), the high affinity receptor for pro-neurotrophins. Likewise, we show that BDNF and TrkB transcripts (and not p75(NTR)) are overexpressed in the patients' tumors by comparison with their adjacent normal tissues, notably in advanced stages of CRC. CONCLUSION: Taken together, these results highlight that BDNF and TrkB are essential for CRC cell growth and survival in vitro and in tumors. This autocrine loop could be of major importance to define new targeted therapies

Sortilin Modulates Schwann Cell Signaling and Remak Bundle Regeneration Following Nerve Injury

Peripheral nerve regeneration relies on the ability of Schwann cells to support the regrowth of damaged axons. Schwann cells re-differentiate when reestablishing contact with the sprouting axons, with large fibers becoming remyelinated and small nociceptive fibers ensheathed and collected into Remak bundles. We have previously described how the receptor sortilin facilitates neurotrophin signaling in peripheral neurons via regulated trafficking of Trk receptors. This study aims to characterize the effects of sortilin deletion on nerve regeneration following sciatic crush injury. We found that Sort1(-)(/)(-) mice displayed functional motor recovery like that of WT mice, with no detectable differences in relation to nerve conduction velocities and morphological aspects of myelinated fibers. In contrast, we found abnormal ensheathment of regenerated C-fibers in injured Sort1(-)(/)(-) mice, demonstrating a role of sortilin for Remak bundle formation following injury. Further studies on Schwann cell signaling pathways showed a significant reduction of MAPK/ERK, RSK, and CREB phosphorylation in Sort1(-)(/)(-) Schwann cells after stimulation with neurotrophin-3 (NT-3), while Schwann cell migration and myelination remained unaffected. In conclusion, our results demonstrate that loss of sortilin blunts NT-3 signaling in Schwann cells which might contribute to the impaired Remak bundle regeneration after sciatic nerve injury