Combination of different noninvasive brain stimulation treatments for upper limb recovery in stroke patients: A systematic review.

We report a review of Pubmed (Medline), CENTRAL, Web of Science, and Scopus to test the effectiveness of the combined application of repetitive transcranial magnetic stimulation and transcranial direct current stimulation in the improvement of different functional variables of the upper limb in people with stroke. Two independent reviewers assessed eligibility and evaluated the quality of the studies. Five articles were included in the final review according to the inclusion criteria: Most show statistically significant differences in motor function improvement in favor of the experimental group, but not in activity. Due to the heterogeneity of the observed studies, the results should be interpreted with caution-more high-quality studies are needed to investigate the effectiveness of these interventions in different stages of stroke patients.

Can a specific biobehavioral-based therapeutic education program lead to changes in pain perception and brain plasticity biomarkers in chronic pain patients? A study protocol for a randomized clinical trial.

BACKGROUND: Chronic pain conditions are complex multifactorial disorders with physical, psychological, and environmental factors contributing to their onset and persistence. Among these conditions, the role of brain-derived neurotrophic factor (BDNF) and the impact of a specific therapeutic education (TE) on pain management have emerged as important areas of research. OBJECTIVE: This study aims to investigate the effects of a specific type of therapeutic education on pain levels and BDNF concentrations. METHODS: In this single-blind, randomized clinical trial, patients will be randomly assigned to one of two groups: one will receive exercise with TE and the other without TE. Assessments will be made at baseline, mid-treatment, post-intervention, and at one and eight months. OUTCOMES: This study will shed light on the effectiveness of a therapeutic education (TE) program in pain management. Additionally, it will provide information on its effects on BDNF levels, a biomarker of brain plasticity, as well as on various psychosocial variables that can influence pain experience. CONCLUSION: By comprehensively addressing the need to quantify brain changes more precisely in individuals with chronic pain during interventions like TE and recognizing the importance of establishing a more structured and comprehensive protocol, this study lays a solid and replicable foundation for future evidence-based treatment developments.

Formation of an invasion-permissive matrix requires TGFß/SNAIL1-regulated alternative splicing of fibronectin.

BACKGROUND: As in most solid cancers, the emergence of cells with oncogenic mutations in the mammary epithelium alters the tissue homeostasis. Some soluble factors, such as TGFß, potently modify the behavior of healthy stromal cells. A subpopulation of cancer-associated fibroblasts expressing a TGFß target, the SNAIL1 transcription factor, display myofibroblastic abilities that rearrange the stromal architecture. Breast tumors with the presence of SNAIL1 in the stromal compartment, and with aligned extracellular fiber, are associated with poor survival prognoses. METHODS: We used deep RNA sequencing and biochemical techniques to study alternative splicing and human tumor databases to test for associations (correlation t-test) between SNAIL1 and fibronectin isoforms. Three-dimensional extracellular matrices generated from fibroblasts were used to study the mechanical properties and actions of the extracellular matrices on tumor cell and fibroblast behaviors. A metastatic mouse model of breast cancer was used to test the action of fibronectin isoforms on lung metastasis. RESULTS: In silico studies showed that SNAIL1 correlates with the expression of the extra domain A (EDA)-containing (EDA+) fibronectin in advanced human breast cancer and other types of epithelial cancers. In TGFß-activated fibroblasts, alternative splicing of fibronectin as well as of 500 other genes was modified by eliminating SNAIL1. Biochemical analyses demonstrated that SNAIL1 favors the inclusion of the EDA exon by modulating the activity of the SRSF1 splicing factor. Similar to Snai1 knockout fibroblasts, EDA- fibronectin fibroblasts produce an extracellular matrix  that does not sustain TGFß-induced fiber organization, rigidity, fibroblast activation, or tumor cell invasion. The presence of EDA+ fibronectin changes the action of metalloproteinases on fibronectin fibers. Critically, in an mouse orthotopic breast cancer model, the absence of the fibronectin EDA domain completely prevents lung metastasis. CONCLUSIONS: Our results support the requirement of EDA+ fibronectin in the generation of a metastasis permissive stromal architecture in breast cancers and its molecular control by SNAIL1. From a pharmacological point of view, specifically blocking EDA+ fibronectin deposition could be included in studies to reduce the formation of a pro-metastatic environment.

Visually-Induced Motor Imagery Effects on Motor Adaptation to Reverse Steering Cycling. A Randomized Controlled Trial.

Purpose: First, testing an intervention of neuromodulation based on motor imagery and action observation as a promoter of motor adaptation of a complex motor task involving balance. Second, determining what prior balance factors can affect the motor adaptation task. Methods: A double-blind randomized controlled trial was performed. Forty-eight healthy subjects were recruited. The balance of all participants during gait and standing was assessed before adapting to the complex, multi-limb motor task of riding an inverse steering bicycle (ISB). Two interventions were carried out interleaved among trials of adaptation to the motor task: the experimental group (n = 24) was asked to perform neuromodulation (EN) by watching first-person ISB riding through immersive VR glasses and, simultaneously, mentally mimicking the movements. The control group (CG) was asked to watch a slideshow video of steady landscape images. Results: The results showed that the EN group did not improve the motor adaptation rate and induced higher adaptation times with respect to the CG. However, while the motor adaptation success showed a significant dependence on the prior proprioceptive participation in balance in the CG, the EN group did not present any relationship between the prior balance profile and motor adaptation outcome. Conclusions: Results point to a benefit of the visually guided neuromodulation for the motor adaptation of the subjects with low participation of proprioception in balance. Moreover, the results from the control group would allow to disclose prognostic factors about the success of the motor adaptation, and also prescription criteria for the proposed neuromodulation based on the balance profile.

Comparative Analysis of Power Consumption between MQTT and HTTP Protocols in an IoT Platform Designed and Implemented for Remote Real-Time Monitoring of Long-Term Cold Chain Transport Operations.

IoT platforms for the transportation industry are portable with limited battery life and need real-time and long-term monitoring operations. Since MQTT and HTTP are widely used as the main communication protocols in the IoT, it is imperative to analyze their power consumption to provide quantitative results that help maximize battery life in IoT transportation systems. Although is well known that MQTT consumes less power than HTTP, a comparative analysis of their power consumption with long-time tests and different conditions has not yet been conducted. In this sense, a design and validation of an electronic cost-efficient platform system for remote real-time monitoring is proposed using a NodeMCU module, in which experimentation is carried out for HTTP and MQTT with different QoS levels to make a comparison and demonstrate the differences in power consumption. Furthermore, we characterize the behavior of the batteries in the systems and compare the theoretical analysis with real long-time test results. The experimentation using the MQTT protocol with QoS 0 and 1 was successful, resulting in power savings of 6.03% and 8.33%, respectively, compared with HTTP, demonstrating many more hours in the duration of the batteries, which could be very useful in technological solutions for the transport industry.

Analyzing the role of cancer-associated fibroblast activation on macrophage polarization.

Snail1 is a transcriptional factor required for cancer-associated fibroblast (CAF) activation, and mainly detected in CAFs in human tumors. In the mouse mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT) model of murine mammary gland tumors, Snai1 gene deletion, besides increasing tumor-free lifespan, altered macrophage differentiation, with fewer expressing low levels of MHC class II. Snail1 was not expressed in macrophages, and in vitro polarization with interleukin-4 (IL4) or interferon-γ (IFNγ) was not altered by Snai1 gene depletion. We verified that CAF activation modified polarization of naïve bone-marrow-derived macrophages (BMDMΦs). When BMDMΦs were incubated with Snail1-expressing (active) CAFs or with conditioned medium derived from these cells, they exhibited a lower cytotoxic capability than when incubated with Snail1-deleted (inactive) CAFs. Gene expression analysis of BMDMΦs polarized by conditioned medium from wild-type or Snai1-deleted CAFs revealed that active CAFs differentially stimulated a complex combination of genes comprising genes that are normally induced by IL4, downregulated by IFNγ, or not altered during the two canonical differentiations. Levels of RNAs relating to this CAF-induced alternative polarization were sensitive to inhibitors of factors specifically released by active CAFs, such as prostaglandin E2 and TGFß. Finally, CAF-polarized macrophages promoted the activation of the immunosuppressive regulatory T cells (T-regs). Our results imply that an active CAF-rich tumor microenvironment induces the polarization of macrophages to an immunosuppressive phenotype, preventing the macrophage cytotoxic activity on tumor cells and enhancing the activation of T-reg cells.

Effect of Different Physical Therapy Interventions on Brain-Derived Neurotrophic Factor Levels in Chronic Musculoskeletal Pain Patients: A Systematic Review.

OBJECTIVE: The main objectives of this review were, firstly, to study the effect of different physiotherapy interventions on BDNF levels, and, secondly, to analyze the influence of physiotherapy on pain levels to subsequently draw conclusions about its possible relationship with BDNF. BACKGROUND: Based on the theory that neurotrophic factors such as BDNF play a fundamental role in the initiation and/or maintenance of hyperexcitability of central neurons in pain, it was hypothesized that the levels of this neurotrophic factor may be modified by the application of therapeutic interventions, favoring a reduction in pain intensity. METHODS: A literature search of multiple electronic databases (Pubmed, PsycINFO, Medline (Ebsco), Scopus, WOS, Embase) was conducted to identify randomized control trials (RCTs) published without language restrictions up to and including March 2022. The search strategy was based on the combination of medical terms (Mesh) and keywords relating to the following concepts: "pain", "chronic pain", "brain derived neurotrophic factor", "BDNF", "physiotherapy", and "physical therapy". A total of seven papers were included. RESULTS: There were two studies that showed statistically significant differences in pain intensity reduction and an increase in the BDNF levels that used therapies such as rTMS and EIMS in patients with chronic myofascial pain. However, the same conclusions cannot be drawn for the other physical therapies applied. CONCLUSIONS: rTMS and EIMS interventions achieved greater short-term reductions in pain intensity and increased BDNF over other types of interventions in chronic myofascial pain patients, as demonstrated by a moderate amount of evidence. In contrast, other types of physical therapy (PT) interventions did not appear to be more effective in decreasing pain intensity and increasing BDNF levels than placebo PT or minimal intervention, as a low amount of evidence was found.

Noncanonical Wnt signaling promotes colon tumor growth, chemoresistance and tumor fibroblast activation.

Colon tumors of the mesenchymal subtype have the lowest overall survival. Snail1 is essential for the acquisition of this phenotype, characterized by increased tumor stemness and invasion, and high resistance to chemotherapy. Here, we find that Snail1 expression in colon tumor cells is dependent on an autocrine noncanonical Wnt pathway. Accordingly, depletion of Ror2, the co-receptor for noncanonical Wnts such as Wnt5a, potently decreases Snail1 expression. Wnt5a, Ror2, and Snail1 participate in a self-stimulatory feedback loop since Wnt5a increases its own synthesis in a Ror2- and Snail1-dependent fashion. This Wnt5a/Ror2/Snail1 axis controls tumor invasion, chemoresistance, and formation of tumor spheres. It also stimulates TGFß synthesis; consequently, tumor cells expressing Snail1 are more efficient in activating cancer-associated fibroblasts than the corresponding controls. Ror2 downmodulation or inhibition of the Wnt5a pathway decreases Snail1 expression in primary colon tumor cells and their ability to form tumors and liver metastases. Finally, the expression of SNAI1, ROR2, and WNT5A correlates in human colon and other tumors. These results identify inhibition of the noncanonical Wnt pathway as a putative colon tumor therapy.

LCOR mediates interferon-independent tumor immunogenicity and responsiveness to immune-checkpoint blockade in triple-negative breast cancer.

Ligand-dependent corepressor (LCOR) mediates normal and malignant breast stem cell differentiation. Cancer stem cells (CSCs) generate phenotypic heterogeneity and drive therapy resistance, yet their role in immunotherapy is poorly understood. Here we show that immune-checkpoint blockade (ICB) therapy selects for LCORlow CSCs with reduced antigen processing/presentation machinery (APM) driving immune escape and ICB resistance in triple-negative breast cancer (TNBC). We unveil an unexpected function of LCOR as a master transcriptional activator of APM genes binding to IFN-stimulated response elements (ISREs) in an IFN signaling-independent manner. Through genetic modification of LCOR expression, we demonstrate its central role in modulation of tumor immunogenicity and ICB responsiveness. In TNBC, LCOR associates with ICB clinical response. Importantly, extracellular vesicle (EV) Lcor-messenger RNA therapy in combination with anti-PD-L1 overcame resistance and eradicated breast cancer metastasis in preclinical models. Collectively, these data support LCOR as a promising target for enhancement of ICB efficacy in TNBC, by boosting of tumor APM independently of IFN.

Effects of motor imagery on strength, range of motion, physical function, and pain intensity in patients with total knee arthroplasty: A systematic review and meta-analysis.

BACKGROUND: In the early stages of total knee arthroplasty (TKA) rehabilitation, in which physical function in general can be affected, motor imagery (MI) might play a relevant role. OBJECTIVE: To assess the impact of MI on strength, active range of motion (ROM), pain intensity, and physical function in patients with TKA. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials. Pooled effects were calculated as standardised mean differences (SMDs) and 95% confidence intervals (CIs) for the relevant outcomes using random effects model. The certainty of evidence was assessed with GRADE approach. RESULTS: This review included 7 articles. The addition of MI to standard therapy, based on low quality of evidence, showed a moderate increase in quadriceps strength (4 studies; SMD: 0.88; 95% CI: 0.42, 1.34) and a small reduction in pain intensity (SMD: 0.63; 95% CI: 0.08, 1.19). It is unclear whether MI can provide beneficial effects for active ROM and function. CONCLUSIONS: There is low to very low-quality evidence that adding an MI intervention to standard rehabilitation for patients with TKA may improve quadriceps strength and pain intensity, but the effects of MI on ROM and physical function is unclear.

Snail1 expression in endothelial cells controls growth, angiogenesis and differentiation of breast tumors.

Snail1 is a transcriptional factor required for epithelial to mesenchymal transition and activation of cancer-associated fibroblasts (CAF). Apart from that, tumor endothelial cells also express Snail1. Here, we have unraveled the role of Snail1 in this tissue in a tumorigenic context. Methods: We generated transgenic mice with an endothelial-specific and inducible Snail1 depletion. This murine line was crossed with MMTV-PyMT mice that develop mammary gland tumors and the consequence of Snail1 depletion in the endothelium were investigated. We also interfere Snail1 expression in cultured endothelial cells. Results: Specific Snail1 depletion in the endothelium of adult mice does not promote an overt phenotype; however, it delays the formation of mammary gland tumors in MMTV-PyMT mice. These effects are associated to the inability of Snail1-deficient endothelial cells to undergo angiogenesis and to enhance CAF activation in a paracrine manner. Moreover, tumors generated in mice with endothelium-specific Snail1 depletion are less advanced and show a papillary phenotype. Similar changes on onset and tumor morphology are observed by pretreatment of MMTV-PyMT mice with the angiogenic inhibitor Bevacizumab. Human breast papillary carcinomas exhibit a lower angiogenesis and present lower staining of Snail1, both in endothelial and stromal cells, compared with other breast neoplasms. Furthermore, human breast tumors datasets show a strong correlation between Snail1 expression and high angiogenesis. Conclusion: These findings show a novel role for Snail1 in endothelial cell activation and demonstrate that these cells impact not only on angiogenesis, but also on tumor onset and phenotype.

Preclinical and Clinical Characterization of Fibroblast-derived Neuregulin-1 on Trastuzumab and Pertuzumab Activity in HER2-positive Breast Cancer.

PURPOSE: To characterize expression of neuregulin-1 (NRG1), an HER3 ligand, in HER2-positive breast cancer and its relation with the efficacy of trastuzumab with or without pertuzumab. EXPERIMENTAL DESIGN: Characterization of NRG1 expression in tumor cell lines, in tumor specimens, and in cancer-associated fibroblasts (CAFs). Patient-derived CAFs were used to investigate NRG1 impact on the activity of trastuzumab with or without pertuzumab in HER2-positive breast cancer cells. The relationship between NRG1 expression and pathologic response to anti-HER2-based neoadjuvant therapy was assessed in a retrospective patient cohort and in the NeoSphere trial. RESULTS: NRG1 was expressed in HER2-positive breast cancer-derived fibroblasts at significantly higher levels than in cancer cells. NRG1 and the conditioned media (CM) from CAFs phosphorylated HER3 and AKT in cancer cells and mediated trastuzumab resistance. Stable genetic depletion of NRG1 from CAFs overcame trastuzumab resistance. Pertuzumab effectively suppressed trastuzumab resistance mediated by either NRG1 or CAF's CM. NRG1 engaged an epithelial-to-mesenchymal transition that was prevented by trastuzumab and pertuzumab. In clinical samples, stromal and/or tumor cell expression of NRG1 determined by immunohistochemistry was uncommon (13.2%) yet significantly linked with residual disease following trastuzumab-based neoadjuvant therapy. In the NeoSphere trial, the magnitude of the difference of pathologic complete response rates favoring the pertuzumab arm was higher in the NRG1-high group. CONCLUSIONS: CAF-derived NRG1 mediates trastuzumab resistance through HER3/AKT, which might be reverted by pertuzumab. In patients with HER2-positive breast cancer, high expression of NRG1 was associated to poor response to trastuzumab, but not in combination with pertuzumab.

Glutamine-Directed Migration of Cancer-Activated Fibroblasts Facilitates Epithelial Tumor Invasion.

Tumors are complex tissues composed of transformed epithelial cells as well as cancer-activated fibroblasts (CAF) that facilitate epithelial tumor cell invasion. We show here that CAFs and other mesenchymal cells rely much more on glutamine than epithelial tumor cells; consequently, they are more sensitive to inhibition of glutaminase. Glutamine dependence drove CAF migration toward this amino acid when cultured in low glutamine conditions. CAFs also invaded a Matrigel matrix following a glutamine concentration gradient and enhanced the invasion of tumor cells when both cells were cocultured. Accordingly, glutamine directed invasion of xenografted tumors in immunocompromised mice. Stimulation of glutamine-driven epithelial tumor invasion by fibroblasts required previous CAF activation, which involved the TGFß/Snail1 signaling axis. CAFs moving toward Gln presented a polarized Akt2 distribution that was modulated by the Gln-dependent activity of TRAF6 and p62 in the migrating front, and depletion of these proteins prevented Akt2 polarization and Gln-driven CAF invasion. Our results demonstrate that glutamine deprivation promotes CAF migration and invasion, which in turn facilitates the movement of tumor epithelial cells toward nutrient-rich territories. These results provide a novel molecular mechanism for how metabolic stress enhances invasion and metastasis. SIGNIFICANCE: Cancer-associated fibroblasts migrate and invade toward free glutamine and facilitate invasion of tumor epithelial cells, accounting for their movement away from the hostile conditions of the tumor towards nutrient-rich adjacent tissues. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/2/438/F1.large.jpg.

Prior cortical activity differences during an action observation plus motor imagery task related to motor adaptation performance of a coordinated multi-limb complex task.

Motor adaptation is the ability to develop new motor skills that makes performing a consolidated motor task under different psychophysical conditions possible. There exists a proven relationship between prior brain activity at rest and motor adaptation. However, the brain activity at rest is highly variable both between and within subjects. Here we hypothesize that the cortical activity during the original task to be later adapted is a more reliable and stronger determinant of motor adaptation. Consequently, we present a study to find cortical areas whose activity, both at rest and during first-person virtual reality simulation of bicycle riding, characterizes the subjects who did and did not adapt to ride a reverse steering bicycle, a complex motor adaptation task involving all limbs and balance. The results showed that cortical activity differences during the simulated task were higher, more significant, spatially larger, and spectrally wider than at rest for good performers. In this sense, the activity of the left anterior insula, left dorsolateral and ventrolateral inferior prefrontal areas, and left inferior premotor cortex (action understanding hub of the mirror neuron circuit) during simulated bicycle riding are the areas with the most descriptive power for the ability of adapting the motor task. Trials registration Trial was registered with the NIH Clinical Trials Registry (clinicaltrials.gov), with the registration number NCT02999516 (21/12/2016).

Hip-Joint Posture and Movement Alterations Are Associated With High Interference of Pain in the Life of Patients With Greater Trochanteric Pain Syndrome.

OBJECTIVE: Greater trochanteric pain syndrome (GTPS) is a common condition that can cause lateral hip pain. The single-leg-squat test (SLST) may be used by physicians in primary care environments to evaluate patients' dynamic stability. The aim of this study was to evaluate the dynamic stability and strength of lateral abduction hip movements in primary care patients with GTPS in relation to their perceived pain interference in life. METHODS: A descriptive observational study was carried out in a primary health care center. Fifty-four participants with GTPS were included in this study and divided into lower- and higher-interference groups (n = 30 and 19, respectively) according to the Graded Chronic Pain Scale. Participants were evaluated for their lateral abduction hip strength and the SLST. RESULTS: The SLST showed a statistically significant difference between groups with respect to hip-joint posture and movement level (P = .043) but not for other SLST domains or lateral abduction hip strength (P > .05). CONCLUSION: Patients with GTPS with more pain interference in their lives had poorer dynamic stability with respect to hip-joint posture and movements based on the SLST but did not present impaired lateral hip abduction strength in comparison with those who perceived lower pain interference in life.

Amygdala stimulation ameliorates memory impairments and promotes c-Fos activity in fimbria-fornix-lesioned rats.

Recently we provided data showing that amygdala stimulation can ameliorate spatial memory impairments in rats with lesion in the fimbria-fornix (FF). The mechanisms for this improvement involve early gene expression and synthesis of BDNF, MAP-2, and GAP43 in the hippocampus and prefrontal cortex. Now we have studied which brain structures are activated by the amygdala using c-Fos as a marker of neural activation. First, we studied neuronal activation after tetanic stimulation to the amygdala in intact rats. We then carried out a second study in FF-lesioned rats in which the amygdala was stimulated 15 min after daily spatial memory training in the water maze. Our results showed that amygdala stimulation produces widespread brain activation, that includes cortical, thalamic, and brain stem structures. Activation was particularly intense in the dentate gyrus and the prefrontal cortex. Training in the water maze increased c-Fos positive nuclei in the dentate gyrus of the hippocampus and in medial prefrontal cortex. Amygdala stimulation to trained FF-lesioned rats induced an increase of neural activity in the dentate gyrus and medial prefrontal cortex relative to the FF-lesioned, but not stimulated group, like the c-Fos activity seen in trained control rats. Based on these and previous results we explain the mechanisms of amygdala reinforcement of neural plasticity and the partial recovery of spatial memory deficits.

Extracellular Granzyme A Promotes Colorectal Cancer Development by Enhancing Gut Inflammation.

If not properly regulated, the inflammatory immune response can promote carcinogenesis, as evident in colorectal cancer (CRC). Aiming to gain mechanistic insight into the link between inflammation and CRC, we perform transcriptomics analysis of human CRC, identifying a strong correlation between expression of the serine protease granzyme A (GzmA) and inflammation. In a dextran sodium sulfate and azoxymethane (DSS/AOM) mouse model, deficiency and pharmacological inhibition of extracellular GzmA both attenuate gut inflammation and prevent CRC development, including the initial steps of cell transformation and epithelial-to-mesenchymal transition. Mechanistically, extracellular GzmA induces NF-κB-dependent IL-6 production in macrophages, which in turn promotes STAT3 activation in cultured CRC cells. Accordingly, colon tissues from DSS/AOM-treated, GzmA-deficient animals present reduced levels of pSTAT3. By identifying GzmA as a proinflammatory protease that promotes CRC development, these findings provide information on mechanisms that link immune cell infiltration to cancer progression and present GzmA as a therapeutic target for CRC.

Widespread impairment of tactile spatial acuity and sensory-motor control in patients with chronic nonspecific neck pain with neuropathic features.

OBJECTIVE: To assess differences in tactile spatial acuity and in sensory-motor control between patients with chronic nonspecific neck pain (CNSNP) with and without neuropathic features (NF), as well as asymptomatic. METHODS: 183 participants were included, 135 had CNSNP classified by the Self-report version of Leeds Assessment of Neuropathic Symptoms and Signs scale in order to identify pain with NF: (1) CNSNP with NF (n = 67), (2) CNSNP with No-NF (n = 68), and (3) asymptomatic subjects (n = 48). The following tests in the following order were assessed after determining the participants' clinical characteristics: 1) two-point discrimination, 2) joint position error, and 3) craniocervical flexion test. RESULTS: Both neck pain groups showed a significant reduction in their ability to discriminate two points in the trapezium and masseter, as well as a significant deficit of a moderate to large magnitude in craniocervical motor control compared with the asymptomatic group. However, only the CNSNP with NF group showed a significant impairment of the two-point discrimination in the tibia (d = 0.57) and a significant impairment of the kinesthetic sense (neck rotation, d = 0.73; neck lateroflexion, d = 0.69), compared with the asymptomatic group. Significant differences in pain intensity, disability and psychological factors between the CNSNP groups were also found, observing the poorest results in the NF group. CONCLUSIONS: Patients with CNSNP with NF have a greater sensory, motor and psychological impairment than those without NF, more pain intensity, disability and negative psychological factors, as well as more impaired tactile spatial acuity in areas remote to the pain and impaired cervical kinesthetic sense.

How Much Is Needed? Comparison of the Effectiveness of Different Pain Education Dosages in Patients with Fibromyalgia.

OBJECTIVE: To assess the effect of different dosages of pain neuroscience education (PNE) programs on central nociceptive processing in patients with fibromyalgia. Second, to compare the effects of different dosages of PNE programs on numerical pain rating scale (NPRS), disability, and psychological variables. DESIGN: Single-blind randomized controlled trial. SETTING: Three fibromyalgia centers in Spain (Valencia, Alcorcón, Alcalá de Henares). SUBJECTS: Seventy-seven patients with fibromyalgia. METHODS: Participants were randomized to four groups of PNE: 1) high-dose PNE (N = 20), 2) low-concentrated dose PNE (N = 20), 3) diluted low-dose PNE (N = 20), and (4) control treatment (N = 17), conducted in two 30-50-minute sessions in groups of four to six participants. Conditioned pain modulation (CPM), temporal summation (TS), and pressure pain thresholds (PPTs) were assessed at baseline and at three-month follow-up. Secondary outcome measures were the Fibromyalgia Impact Questionnaire, Pain Catastrophizing Scale, and Pain Anxiety Symptoms Scale. RESULTS: There were significant between-group differences for NPRS in favor of the groups receiving high-dose PNE, with a large effect size at three-month follow-up (P < 0.01, η2p = 0.170), but there were no significant differences between groups for the remaining variables (P > 0.05). All groups improved for central nociceptive processing, psychological variables, disability, and pain intensity (NPRS). CONCLUSIONS: In patients with fibromyalgia, higher dosages of PNE produced a larger improvement in pain severity at three-month follow-up than other dosages of PNE and biomedical education. However, PNE was not superior to biomedical education in the central nociceptive processing, disability, or psychological variables in patients with fibromyalgia.

Patient-reported outcomes measured with and without dizziness associated with non-specific chronic neck pain: implications for primary care.

BACKGROUND: The aim of this study was to compare health-related quality of life (HRQoL) and disability and fear of movement in patients with non-specific chronic neck pain (NSCNP) associated with dizziness with respect to patients with isolated NSCNP in primary care settings. METHODS: A cross-sectional study was carried out in a primary care center. A total of 120 patients were divided into two groups and analyzed in this study. One group of patients reported dizziness combined with NSCNP (n = 60), and the other reported no dizziness with their NSCNP (n = 60). Patient-reported outcome measurements were HRQoL (primary outcome) and disability and kinesiophobia (secondary outcomes) assessed by the EuroQoL Five Dimensions and Five Levels (EQ-5D-5L), neck disability index (NDI) and Tampa Scale of Kinesiophobia (TSK-11), respectively. RESULTS: Statistically significant differences (P < 0.05) for a 95% confidence interval (CI) with a large effect size (Cohen d) were found between both groups with greater values of disability (mean difference = 6.30 points; 95% CI [3.84-8.75]; d = 0.94) and kinesiophobia (mean difference = 8.36 points; 95% CI [6.07-10.65]; d = 1.33), and an impairment of HRQoL (mean difference = 16.16 points; 95% CI [11.09-21.23]; d = 1.16), for patients with NSCNP associated with dizziness with respect to patients with isolated NSCNP. CONCLUSIONS: Patients with NSCNP in conjunction with dizziness present higher HRQoL impairment and higher disability and kinesiophobia compared to patients with isolated NSCNP.