The stress regulator FKBP51: a novel and promising druggable target for the treatment of persistent pain states across sexes

It is well established that FKBP51 regulates the stress system by modulating the sensitivity of the glucocorticoid receptor to stress hormones. Recently, we have demonstrated that FKBP51 also drives long-term inflammatory pain states in male mice by modulating glucocorticoid signalling at spinal cord level. Here, we explored the potential of FKBP51 as a new pharmacological target for the treatment of persistent pain across the sexes. First, we demonstrated that FKBP51 regulates long-term pain states of different aetiologies independently of sex. Deletion of FKBP51 reduced the mechanical hypersensitivity seen in joint inflammatory and neuropathic pain states in female and male mice. Furthermore, FKBP51 deletion also reduced the hypersensitivity seen in a translational model of chemotherapy-induced pain. Interestingly, these 3 pain states were associated with changes in glucocorticoid signalling, as indicated by the increased expression, at spinal cord level, of the glucocorticoid receptor isoform associated with glucocorticoid resistance, GRβ, and increased levels of plasma corticosterone. These pain states were also accompanied by an upregulation of interleukin-6 in the spinal cord. Crucially, we were able to pharmacologically reduce the severity of the mechanical hypersensitivity seen in these 3 models of persistent pain with the unique FKBP51 ligand SAFit2. When SAFit2 was combined with a state-of-the-art vesicular phospholipid gel formulation for slow release, a singl...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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Rationale: Ependymomas are neuroepithelial tumors that typically occur in the central nervous system. Ependymomas arising in the mediastinum are exceedingly rare, with only approximately 9 isolated cases reported in the literature to date. Patient concerns: A 35-year-old woman was referred to our hospital with complaints of progressive back pain for 3 months. Physical examination revealed decreased breathing sounds and tenderness. Contrast-enhanced computed tomography showed a soft tissue mass with heterogeneous enhancement in the right posterior mediastinum. Diagnoses: The diagnosis of primary mediastinal ependymo...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
What is Vicodin and What Does It Do? According to MedicineNet, Vicodin is a combination of Hydrocodone and Acetaminophen. Hydrocodone is a narcotic pain-reliever and a cough suppressant, similar to codeine. Hydrocodone blocks the receptors on nerve cells in the brain that give rise to the sensation of pain. Acetaminophen is a non-narcotic pain reliever and fever reducer. Acetaminophen works by elevating the threshold to pain. Essentially, in order for pain to be felt, s greater stimulation of the nerves responsible for the sensation of pain is necessary. It reduces fever through its action on the temperature-regulating ce...
Source: Cliffside Malibu - Category: Addiction Authors: Tags: Addiction Addiction Recovery Detox Resources for Alcohol and Drugs/Opiates Drug Rehab Information Drug Treatment anxiety in withdrawal vicodin withdrawal symptoms Source Type: blogs
CONCLUSION: Radiation therapy is the standard treatment for solitary bone plasmocytoma. It ensures good local control in 90% of cases. The prognosis is affected by progression to multiple myeloma, which justifies rigorous monitoring after treatment and suggests a reflection on the exact place of chemotherapy. PMID: 31677902 [PubMed - as supplied by publisher]
Source: Cancer Radiotherapie - Category: Cancer & Oncology Authors: Tags: Cancer Radiother Source Type: research
In this study we demonstrate that VCR also activates endothelial cells in the murine central nervous system, increases paracellular permeability and decreases trans endothelial resistance. In in vivo imaging studies in mice, VCR administration results in trafficking of inflammatory monocytes through the endothelium. Indeed, VCR treatment affects the integrity of the blood-spinal cord-barrier as indicated by Evans Blue extravasation, disrupts tight junction coupling and is accompanied by the presence of monocytes in the spinal cord. Such inflammatory monocytes (Iba-1+ CCR2+ Ly6C+ TMEM119- cells) that infiltrate the spinal c...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research
In this study we demonstrate that VCR also activates endothelial cells in the murine central nervous system, increases paracellular permeability and decreases trans endothelial resistance. In in vivo imaging studies in mice, VCR administration results in trafficking of inflammatory monocytes through the endothelium. Indeed, VCR treatment affects the integrity of the blood-spinal cord-barrier as indicated by Evans Blue extravasation, disrupts tight junction coupling and is accompanied by the presence of monocytes in the spinal cord. Such inflammatory monocytes (Iba-1+ CCR2+ Ly6C+ TMEM119- cells) that infiltrate the spinal c...
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun Source Type: research
-García EM Abstract The main goal of treatment in spinal metastatic patients is local control of the disease, pain relief and the maintenance of ambulation. Traditionally, wide surgical resection of the tumour followed by adjuvant radiation and/or chemotherapy has been recommended. Currently, single-fraction or hypofractionated stereotactic body radiation therapy (SBRT) yields a one-year local control rate of over 95% with minimum morbidity, even for tumours previously considered radioresistant. In addition, by posterolateral and circumferential decompression and stabilisation of the spinal cord, it is feas...
Source: Neurocirugia - Category: Neurosurgery Authors: Tags: Neurocirugia (Astur) Source Type: research
ConclusionsSpinal LGG is a rare entity with significant long-term effects. Although surgery is the most common initial treatment option, more in-depth analysis of molecular biomarkers may improve stratification and prognostication.
Source: Journal of Neuro-Oncology - Category: Cancer & Oncology Source Type: research
Authors: Yang S, Wang D, Xu J, Luo F, Wu W, Zhang Z Abstract Objective: To observe the clinical effect of anterior debridement, decompression, bone grafting, and instrumentation for cervical spinal tuberculosis in four hospitals. Materials and Methods: This research retrospectively analyzed 146 patients with cervical spinal tuberculosis who were treated by anterior debridement, decompression, bone grafting, and instrumentation in four institutions between January 2000 and January 2015. There were 68 males and 78 females with an average age of 31.32 ± 11.69 years. All patients received chemotherapy for 18 mon...
Source: Neurological Research - Category: Neurology Tags: Neurol Res Source Type: research
In this study, we investigated a role for Nrf2/HO-1/CO in mediating vincristine-induced neuroinflammation by inhibiting connexin 43 (Cx43) production in the spinal cord following the intrathecal application of the HO-1 inducer protoporphyrin IX cobalt chloride (CoPP) or inhibitor protoporphyrin IX zinc (ZnPP), and we analyzed the underlying mechanisms by which levo-corydalmine (l-CDL, a tetrahydroprotoberberine) attenuates vincristine-induced pain. Treatment with levo-corydalmine or oxycodone hydrochloride (a semisynthetic opioid analgesic, used as a positive control) attenuated vincristine-induced persistent pain hypersen...
Source: Neurotherapeutics - Category: Neurology Source Type: research
HOLLISTON (CBS) – To spend time with Declan Vail is to experience an elevating joy. Whether he is plucking a guitar in his playroom, putting on a puppet show with his younger brother Teagan or riding in the back of a police car to the Dana Farber Jimmy Fund Clinic, he is the embodiment of happiness. And yet, this bubbly, outgoing three year-old is fighting a brain tumor. An inoperable brain tumor that has thrown his family’s life into–some degree of–chaos and uncertainty. “I think he has always been brave and strong but he is steadfast in it now,” his father, Jeremy told WBZ’s Lisa...
Source: WBZ-TV - Breaking News, Weather and Sports for Boston, Worcester and New Hampshire - Category: Consumer Health News Authors: Tags: Boston News Health Syndicated Local Cancer Declan Vail Lisa Hughes Source Type: news
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