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Regulation of Pain and Itch by TRP Channels

Neuroscience Bulletin 2018年第1期34卷 120-142页

作者： Carlene Moore rupali gupta Sven-Eric Jordt Yong Chen Wolfgang B.Liedtke Department of Neurology Duke University Medical Center Department of Anesthesiology Duke University Medical Center

Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular sensors of chemical, thermal, and mechanical noxious stimuli to evoke the pain and itch sensations. Among them are the TRPA1 channel, members of the vanilloid subfamily （TRPV1, TRPV3, and TRPV4）, and finally members of the melastatin group （TRPM2, TRPM3, and TRPMS）. Given that pain and itch are pro-survival, evolutionarily-honed protective mechanisms, care has to be exercised when developing inhibitory/modulatory com- pounds targeting specific pain/itch-TRPs so that physio- logical protective mechanisms are not disabled to a degree that stimulus-mediated injury can occur. Such events have impeded the development of safe and effective TRPV1- modulating compounds and have diverted substantial resources. A beneficial outcome can be readily accom- plished via simple dosing strategies, and also by incorpo- rating medicinal chemistry design features during compound design and synthesis. Beyond clinical use, where compounds that target more than one channel might have a place and possibly have advantageous features, highly specific and high-potency compounds will be helpful in mechanistic discovery at the structure-function level.

关键词： TRP channels Pain Itch Nociceptors - Inflammation Lipids Temperature Hyperalgesia Nerve damage Neuropathic pain Mechanotransduction Allodynia

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Morbidly Adherent Placenta (MAP): Lessons learnt

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Open Journal of Obstetrics and Gynecology 2013年第1期3卷 217-221页

作者： Leena Wadhwa Sangeeta gupta Pratibha gupta Bhawna Satija rupali Khanna Department of Obstetrics & Gynecology ESI-PGIMSR Basaidarapur Delhi Department of Radiology ESI-PGIMSR Basaidarapur Delhi

Context: Once a rare occurrence, MAP is becoming an increasing threat to maternal lives. Aims: To summarize our experience in the management of patients with morbidly adherent placenta. Introduction: MAP is a potentially life threatening hemorrhagic condition responsible for 7% - 10% maternal mortality. Settings and Design: Tertiary care center. Methods and Material: Retrospective study in which data of twelve patients with clinical diagnosis of morbidly adherent placenta was reviewed from Jan 2009 till Sept 2012. Results: The incidence of placenta accreta was found to be increasing every year. Out of twelve cases with clinical diagnosis of MAP, placenta previa was present in 10/12 patients with MAP. All patients had history of previous section. Two patients with preoperative diagnosis of MAP on USG/MRI were found to be normal intra-operative and in one patient focal accreta was diagnosed intraoperatively. Nine patients of MAP underwent caesarean hysterectomy due to excessive bleeding during placental separation and were confirmed histo-pathologically (3 accreta vera, 3 increta and 3 percreta). Internal iliac artery ligation was done in 2 patients. Two patients with placenta percreta had bladder rupture which was repaired and these two patients subsequently expired. Conclusions: The incidence of placenta accreta is increasing due to higher cesarean section (C/S) rate. Key to successful outcome is awareness, anticipation, preoperative counseling, planning and multidisciplinary approach.

关键词： Placenta Accreta Morbidly Adherent Placenta Cesarean Section Hemorrhage Maternal Mortality

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