Browsing by Subject "NEUROPATHIC PAIN"
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Item Open Access End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain.(Blood advances, 2019-12) Farrell, Ann T; Panepinto, Julie; Carroll, C Patrick; Darbari, Deepika S; Desai, Ankit A; King, Allison A; Adams, Robert J; Barber, Tabitha D; Brandow, Amanda M; DeBaun, Michael R; Donahue, Manus J; Gupta, Kalpna; Hankins, Jane S; Kameka, Michelle; Kirkham, Fenella J; Luksenburg, Harvey; Miller, Shirley; Oneal, Patricia Ann; Rees, David C; Setse, Rosanna; Sheehan, Vivien A; Strouse, John; Stucky, Cheryl L; Werner, Ellen M; Wood, John C; Zempsky, William TTo address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points.Item Open Access General anesthetics activate a potent central pain-suppression circuit in the amygdala.(Nature neuroscience, 2020-05-18) Hua, Thuy; Chen, Bin; Lu, Dongye; Sakurai, Katsuyasu; Zhao, Shengli; Han, Bao-Xia; Kim, Jiwoo; Yin, Luping; Chen, Yong; Lu, Jinghao; Wang, FanGeneral anesthesia (GA) can produce analgesia (loss of pain) independent of inducing loss of consciousness, but the underlying mechanisms remain unclear. We hypothesized that GA suppresses pain in part by activating supraspinal analgesic circuits. We discovered a distinct population of GABAergic neurons activated by GA in the mouse central amygdala (CeAGA neurons). In vivo calcium imaging revealed that different GA drugs activate a shared ensemble of CeAGA neurons. CeAGA neurons also possess basal activity that mostly reflects animals' internal state rather than external stimuli. Optogenetic activation of CeAGA potently suppressed both pain-elicited reflexive and self-recuperating behaviors across sensory modalities and abolished neuropathic pain-induced mechanical (hyper-)sensitivity. Conversely, inhibition of CeAGA activity exacerbated pain, produced strong aversion and canceled the analgesic effect of low-dose ketamine. CeAGA neurons have widespread inhibitory projections to many affective pain-processing centers. Our study points to CeAGA as a potential powerful therapeutic target for alleviating chronic pain.