Rejected

Interstitial Cystitis (IC) is a chronic and rare disease, more frequent in women. Symptoms of continuous pain can produce psychological disorders, such as anxiety and depression. The spread of COVID-19 pandemic added to distress experienced by patients with IC emotions, such as fear, sadness, boredom, frustration and anger.

P2X receptor is an ATP-gated ion channel, mainly localized on peripheral sensory neurons. Currently, several clinical trials are being conducted with P2X receptor antagonists for the treatment of chronic pain or cough. To identify a P2X lead compound, we reexamined the HTS evaluation compounds and selected dioxotriazine derivatives from which we identified a hit compound. As a result of the hit-to-lead SAR, we obtained lead compound 1 which had a moderate inhibitory effect on P2X receptors (IC, 128 nM). Further improvement of the potency and PK profiles of this lead compound finally led to the selected compound 74 (P2X IC, 16.1 nM; P2X IC, 2931 nM), which demonstrated a strong analgesic effect against allodynia on oral administration in the rat partial sciatic nerve ligation model of neuropathic pain (ED, 3.1 mg/kg).

Narcotics are the cornerstone of postoperative pain control, but the opioid epidemic and the negative physiological and psychological effects of narcotics implore physicians to utilize nonpharmacological methods of pain control.

To describe an approach that allows for a dedicated clinical assessment and accurate recognition of peripheral neuropathic pain in primary care and to provide an update on the available pharmacologic therapies MATERIALS AND METHODS: Medline was searched using the key word "neuropathic pain". Searches were refined for each pathophysiological mechanism, diagnosis and treatment by adding appropriate key words.

Individuals with sickle cell disease (SCD) are at risk for painful crises and long-term cardiopulmonary morbidity. Echocardiogram is recommended if signs or symptoms of cardiopulmonary disease develop in previously asymptomatic patients, or worsen in those with known disease. Second-generation echocardiogram contrast agents (ECAs) improve the diagnostic capacity of echocardiogram; however, these agents have risks in SCD populations that have yet to be investigated.

Transient Global Amnesia (TGA) is an enigmatic amnestic syndrome. We conducted a systematic review to investigate the relationship between the conventional cardiovascular risk factors and TGA. MEDLINE, CENTRAL, EMBASE and PsycINFO were comprehensively searched and 23 controlled observational studies were retrieved. The prevalence of hypertension, diabetes mellitus, dyslipidemia and smoking was lower among patients with TGA compared to Transient Ischemic Attack. Regarding the comparison of TGA with healthy individuals, there was strong evidence suggesting a protective effect of diabetes mellitus on TGA and weaker evidence for a protective effect of smoking. Hypertension was associated with TGA only in more severe stages, while dyslipidemia was not related. In view of these findings, a novel pathophysiological hypothesis is proposed, in which the functional interactions of Angiotensin-II type-1 and N-methyl-D-aspartate receptors are of pivotal importance. The whole body of clinical evidence (nature of precipitating events, associations with migraine, gender-based association patterns) was integrated.

Percutaneous iliosacral screw placement has become the technique of choice for treating injuries to the posterior pelvis. However, the technique requires an understanding of the anatomy surrounding the bone corridors to avoid complications and detect them early if they occur. We present the clinical case of a patient with a U-shaped fracture of the sacrum that evolves with gluteal pain and left foot equine paresis after percutaneous fixation with iliosacral screws. Angio-CT of the pelvis shows active arterial bleeding from the superior gluteal artery associated to extensive hematoma in the thickness of the gluteus medius muscle. Emergency embolization is performed by installing coil and gelatin. Successful control of bleeding is achieved. To avoid this complication, a complete imaging study is recommended in planning the surgery and to avoid multiple repositioning of the guide or screw. Arterial injury should be suspected in case of increasing pain despite analgesia, functional impairment or neurological deficit and the angiographic study and resolution by selective embolization of the bleeding vessels must be performed.