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Patients with refractory chronic migraine have poor quality of life. Intravenous infusions are indicated to rapidly 'break the cycle' of pain. Lidocaine infusions may be effective but evidence is limited.
Learn More >Prescription opioids can treat acute pain in primary care but have potential for unsafe use and progression to prolonged opioid prescribing.
Learn More >Chronic pelvic pain (CPP) is a complex, heterogeneous condition affecting both female and male patients with significant effects on quality of life. Chronic pelvic pain is a prevalent but often underdiagnosed condition due to the variation in patient presentation, a gap in communication among specialties, under-reporting of the syndrome, and lack of standardized diagnostic criteria with a subsequent delay in diagnosis. The mechanism of CPP is complex due to multifactorial etiologies of pain and its vast anatomy and innervation. Potential causes of pelvic pain include the nerves, muscles, bone, or organs of the reproductive, gastrointestinal, urological, musculoskeletal, vascular, neurological, and psychological systems.
Learn More >A miniaturized, flexible cooling device can be used for precise analgesia.
Learn More >The mechanisms that link maternal immune activation (MIA) with the onset of neurodevelopmental disorders remain largely unclear. Accelerated puberty is also associated with a heightened risk for psychopathology in later life, but there is a dearth of evidence on the impacts of maternal infection on pubertal timing. We examined the effects of MIA on reproductive development, mechanical allodynia, and sensorimotor gating in juvenile, adolescent, and adult male and female mice. Moreover, we investigated hypothalamic neural markers associated with the reproductive and stress axes. Finally, we tested the mitigating effects of environmental enrichment (EE), which has clinical relevancy in human rehabilitation settings. Our results show that administration of polyinosinic-polycytidylic acid (poly(I:C)) on gestational day 12.5 led to early preputial separation, vaginal openings, and age of first estrus in offspring. MIA exposure altered pain sensitivity across development and modestly altered prepulse inhibition. The downregulation of Nr3c1 and Oprk mRNA in the hypothalamus of juvenile mice suggests that MIA's effects may be mediated through disruption of hypothalamic-pituitary-adrenal axis activity. In contrast, life-long housing with EE rescued many of these MIA-induced consequences. Overall, our findings suggest that accelerated puberty may be associated with the deleterious effects of infection during pregnancy and the onset of psychopathology.
Learn More >T helper 17 (Th17) lymphocytes play a critical role in the pathogenesis of autoimmune diseases, mainly by producing the pro-inflammatory cytokine interleukin-17 (IL-17). Therefore, Th17 lymphocytes have been considered a strategic target for drug discovery and development. In this study, we investigated the activity and possible mechanisms of action of a 4-phenyl coumarin isolated from propolis, named cinnamoyloxy-mammeisin (CNM), in Th17 cell differentiation and the development of experimental Th17-dependent autoimmune encephalomyelitis (EAE). Our data showed that in vitro Th17 cell differentiation was attenuated by CNM treatment in a concentration-dependent manner (1, 3, and 10 μM). This was associated with a reduction in the release of IL-17 (35% inhibition) and interleukin-22 (IL-22, 51% inhibition). Th17-differentiated cells exposed to CNM also downregulated the expression of Th17 hallmarked cell genes, such as RAR-related orphan receptor c (Rorc, 51% inhibition), and interleukin-23 receptor (Il23r, 64% inhibition), indicating possible upstream molecular mechanisms. Mechanistically, CNM significantly reduced the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) during in vitro Th17 cell differentiation. In vivo treatment with CNM (100 μg/kg) reduced the clinical signs of EAE, which was associated with a reduction in Central Nervous System demyelination, neuroinflammation, and Th17 response in the spinal cord and inguinal lymph nodes. Consistent with this, CNM also effectively attenuated human Th17 differentiation in vitro. Collectively, our results highlight the potential of CNM as a new molecule that can modulate Th17 cells via inhibition of STAT3 signaling and, as a result, reduce autoimmune inflammation.
Learn More >Implantable devices capable of targeted and reversible blocking of peripheral nerve activity may provide alternatives to opioids for treating pain. Local cooling represents an attractive means for on-demand elimination of pain signals, but traditional technologies are limited by rigid, bulky form factors; imprecise cooling; and requirements for extraction surgeries. Here, we introduce soft, bioresorbable, microfluidic devices that enable delivery of focused, minimally invasive cooling power at arbitrary depths in living tissues with real-time temperature feedback control. Construction with water-soluble, biocompatible materials leads to dissolution and bioresorption as a mechanism to eliminate unnecessary device load and risk to the patient without additional surgeries. Multiweek in vivo trials demonstrate the ability to rapidly and precisely cool peripheral nerves to provide local, on-demand analgesia in rat models for neuropathic pain.
Learn More >Neuropathic pain (NP) is one of the most intractable diseases. The lack of effective therapeutic measures remains a major problem due to the poor understanding of the cause of NP. The aim of the present study was to investigate the effect of the long non‑coding RNA small nucleolar RNA host gene 5 (SNHG5) in NP and the underlying molecular mechanism in order to identify possible therapeutic targets. A chronic constriction injury (CCI) mouse model was used to investigate whether SNHG5 prevents NP and the inflammatory response. Luciferase and RNA pull‑down assays were used to detect the binding between SNHG5 and miR‑142‑5p as well as between miR‑142‑5p and CAMK2A. Western blot and qPCR were used to detect the RNA and protein expression. The results indicated that SNHG5 significantly inhibited CCI‑induced NP. In addition, SNHG5 inhibited the inflammatory response through decreasing the release and the mRNA expression of interleukin (IL)‑1β, IL‑6, IL‑10 and tumor necrosis factor‑α. Mechanistically, SNHG5 acted via sponging microRNA‑142‑5p, thereby upregulating the expression of calcium/calmodulin‑dependent protein kinase II α (CAMK2A). Further investigation indicated that CAMK2A knockdown also inhibited CCI‑induced NP and inflammation. In summary, the present study demonstrated that SNHG5 silencing could alleviate the neuropathic pain induced by chronic constriction injury via sponging miR‑142‑5p and regulating the expression of CAMK2A.
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