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Mechanical allodynia is a debilitating condition for millions of patients with chronic pain. Mechanical allodynia can manifest in distinct forms, including brush-evoked dynamic and filament-evoked static allodynia. In the nervous system, the forkhead protein Foxo1 plays a critical role in neuronal structures and functions. However, the role of Foxo1 in the somatosensory signal remains unclear. Here, we found that Foxo1 selectively regulated static mechanical pain. Foxo1 knockdown decreased sensitivity to static mechanical stimuli in normal rats and attenuated static mechanical allodynia in rat models for neuropathic, inflammatory, and chemotherapy pain. Conversely, Foxo1 overexpression selectively enhanced sensitivity to static mechanical stimuli and provoked static mechanical allodynia. Furthermore, Foxo1 interacted with voltage gated sodium Nav1.7 channels and increased the Nav1.7 current density by accelerating activation rather than by changing the expression of Nav1.7 in dorsal root ganglia neurons. In addition, the serum level of Foxo1 was found to be increased in chronic pain patients and to be positively correlated with the severity of chronic pain. Altogether, our findings suggest that serum Foxo1 level could be used as a biological marker for prediction and diagnosis of chronic pain. Moreover, selective blockade of Foxo1/Nav1.7 interaction may offer a new therapeutic approach in patients with mechanical pain.
Learn More >Synovitis-associated pain is mediated by inflammatory factors that may include S100A8/9, which is able to stimulate nociceptive neurons via Toll-like receptor 4. In this study, we investigated the role of S100A9 in pain response during acute synovitis.
Learn More >Objectives The cardinal symptom of burning mouth syndrome (BMS) is long-lasting pain and comprehensive health-related quality of life (HRQL) assessments may estimate how well patients with BMS live in relation to their health issues. The aims of the study were to explore general and BMS-specific HRQL based on an HRQL model and to compare HRQL in patients with BMS and age-matched controls. Methods For this case-control study 56 female patients with BMS and 56 female controls completed the following: A general questionnaire with Global items for life satisfaction, general health and oral health; General Population-Clinical Outcomes in Routine Evaluation (GP-CORE); Hospital Anxiety and Depression Scale (HADS); and Oral Health Impact Profile-14 (OHIP-14). Patients with BMS completed additional questionnaires which included BMS-problem severity, a global item for ratings of overall severity perceptions measured by visual analog scale (VAS); and BMS-modified Multidimensional Pain Inventory-Swedish version (MPI-S). BMS-modified MPI-S includes the three subscales Pain severity, Interference and Social support. Results Patients with BMS scored worse on all global items, GP-CORE, HADS and OHIP-14 compared to controls and the differences were large. Patients with severe BMS problems, as defined by a median split on BMS-problem severity, scored worse on the BMS-modified MPI-S subscale Pain severity and the difference was large. Conclusions We found clearly impaired general HRQL in patients with BMS compared to controls. For specific HRQL, the severity of pain was worse among patients with higher overall BMS-problem severity. The HRQL model with global ratings together with physical, psychological and social concepts has capacity to increase comparability and validity of studies, however further evaluations of the measures are needed. The HRQL model may be used over time to increase the understanding of different HRQL aspects and their internal relationships. In clinical settings, with an increased knowledge of one´s own distinctive quality of life abilities and restrictions, the patients with BMS can be guided and supported to manage their long-lasting pain. The HRQL model may be an aid toward bridging distinctions between general and oral health to further encourage collaboration between medicine and odontology.
Learn More >Although it is known that nociceptive stimulation in the first postnatal week in rats is useful to model preterm pain, resulting in activation of specific brain areas, as assessed in vivo using manganese-enhanced magnetic resonance imaging (MEMRI), little is known about its long-term effects and sex specificity. Here we aimed to investigate whether inflammatory pain induced in male and female adult rats modify the pattern of brain activation between animals subjected or not to neonatal pain. For this, Complete Freund's adjuvant (CFA, was injected into the left hind paw of rat pups on postnatal day 1 (P1) or P8 to induce inflammatory response. During adulthood, CFA-treated and control animals were injected with CFA 1 hour prior MRI. MEMRI has the ability to enhance the contrast of selective brain structures in response to a specific stimulus, as the pain. MEMRI responses were consistent with activation of nociceptive pathways and these responses were reduced in animals treated with CFA on P1, but increased in animals treated on P8, mainly in the female group. In agreement, P8 female group showed exacerbated responses in the thermal nociceptive test. By using MEMRI we conclude that the natural ability of adult rats to recognize and react to pain exposition is modified by neonatal painful exposition, mainly among females.
Learn More >To examine longitudinal associations between parent factors (parent headache frequency and disability, protective parenting behaviors, parent catastrophizing) with adolescent headache-related disability and headache frequency over 6 months.
Learn More >N-docosahexaenoyl ethanolamine (DHEA; also known as synaptamide) binds to both the CB1 and CB2 cannabinoid receptors and has anti-inflammatory properties in vitro. However, the in vivo effects of DHEA are unknown. Therefore, this study was designed to understand the effects of DHEA in models of pain and inflammation in mice.
Learn More >Opioids are effective painkillers. However, their risk-benefit ratio is dampened by numerous adverse effects and opioid misuse has led to a public health crisis. Safer alternatives are required but isolating the antinociceptive effect of opioids from their adverse effects is a pharmacological challenge because activation of the mu opioid receptor triggers both the antinociceptive and adverse effects of opioids.
Learn More >Calcitonin gene-related peptide plays a key role in cluster headache pathophysiology. It is released from the trigeminal nerve, which also innervates the eye. In this study, we tested if tear fluid calcitonin gene-related peptide measurement detects elevated calcitonin gene-related peptide levels in cluster headache patients compared to controls.
Learn More >Chronic pain studies investigating the ability to detect sensory processing differences related to thalamic gating using electroencephalographic (EEG) alpha have yielded conflicting results. Alpha's basic psychometric properties in pain populations requires further study. The present study reports on the test-retest reliability and internal consistency of EEG alpha power in older adults with chronic knee pain.
Learn More >Δ-tetrahydrocannabinol (THC), the major psychoactive ingredient of Cannabis sativa, exerts its actions through the endocannabinoid system by stimulation of the cannabinoid type 1 (CB1) receptor. The widespread distribution of this receptor in different neuronal cell types and the plethora of functions that is modulated by the endocannabinoid system explain the versatility of the effects of THC. However, the cell types involved in the different THC effects are still not fully known. Conditional CB1 receptor knock-out mice were previously used to identify CB1 receptor subpopulations that are "necessary" for the tetrad effects of a high dose of THC: hypothermia, hypolocomotion, catalepsy and analgesia. Here, we used mouse models for conditional CB1 receptor "rescue" in dorsal telencephalic glutamatergic and forebrain GABAergic neurons to determine which CB1 receptor subpopulations are "sufficient" for these tetrad effects. Glutamatergic CB1 receptor was not only necessary but also sufficient for THC-induced hypothermia and hypolocomotion. Analgesic and cataleptic effects of THC are largely independent of glutamatergic and GABAergic CB1 receptors, since no sufficiency was found, in agreement with the previously reported lack of necessity. We also revealed a novel aspect of GABAergic CB1 receptor signaling. In animals with CB1 receptors exclusively in forebrain GABAergic neurons, THC stimulated rather than reduced locomotion. This cell-type selective and hitherto unsuspected hyperlocomotive effect may be occluded in wild-types and conditional knockouts and only be exposed when CB1 signaling is absent in all other cell types, thus underlining the importance of investigating both necessary and sufficient functions to unequivocally unravel cell-type specific actions.
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