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Remifentanil-induced hyperalgesia (RIH) is a severe but common postoperative clinical problem with elusive underlying neural mechanisms. Here, we discovered that glutamatergic neurons in the thalamic ventral posterolateral nucleus (VPLGlu) exhibited significantly elevated burst firing accompanied by upregulation of Cav3.1 T-type calcium channel expression and function in RIH model mice. In addition, we identified a glutamatergic neuronal thalamocortical circuit in the VPL projecting to hindlimb primary somatosensory cortex glutamatergic neurons (S1HLGlu) that mediated RIH. In vivo calcium imaging and multi-tetrode recordings revealed heightened S1HLGlu neuronal activity during RIH. Moreover, preoperative suppression of Cav3.1-dependent burst firing in VPLGlu neurons or chemogenetic inhibition of VPLGlu neuronal terminals in the S1HL abolished the increased S1HLGlu neuronal excitability while alleviating RIH. Our findings suggest that remifentanil induces postoperative hyperalgesia by upregulating T-type calcium channel-dependent burst firing in VPLGlu neurons to activate S1HLGlu neurons, thus revealing an ion channel-mediated neural circuit basis for RIH that can guide analgesic development.

In parallel with the decline of renal excretory function, drug dosing of many drugs becomes more challenging. Finding the right dose is even more difficult if kidney replacement therapy is instituted. This is further aggravated by the fact that even for substances with a narrow therapeutic range, drug monitoring is only rarely offered, let alone advocated. This holds also true for gabapentin, an anticonvulsant drug that is increasingly prescribed for indications such as cancer-related pain, restless legs syndrome, migraine, or uremic pruritus. The drug is excreted unchanged in urine, so plasma clearance of gabapentin is directly proportional to creatinine clearance. Hence, renal impairment reduces gabapentin excretion and increases plasma gabapentin concentrations in a linear fashion. Therefore, the elimination half-life of gabapentin is between 5 and 9 h, in patients with normal renal function but increases to 132 h in patients on dialysis. Epidemiological data from the USRDS underline this problem. About 19% of the 140,899 adult USA patients enrolled in Medicare coverage received gabapentin in 2011. Its use was associated with an increased risk of altered mental status, fall, and fracture. We report 2 patients in which overdose of gabapentin occurred. In 1 patient, severe neurological symptoms prompted an extensive diagnostic work up, while the underlying cause of the clinical presentation was a supra-therapeutic drug level of gabapentin. Consequently, symptoms subsided with the discontinuation of the drug. Indication and drug dose of gabapentin in dialysis patients should be tightly controlled, and drug monitoring used to avoid unintended overdose.

Opioid-induced hyperalgesia (OIH) is a state of paradoxically enhanced pain transmission, termed nociceptive sensitization, described to occur in both humans and animals after repeated administration of opioid drugs, including rapidly acting remifentanil. However, molecular mechanisms of OIH remain understudied. In this issue of the JCI, Yan Jin and colleagues provided strong evidence that hyperexcitable thalamocortical networks drive remifentanil-induced hyperalgesia in a rodent model of postsurgical pain. Furthermore, the authors specifically identified an important role of the CaV3.1 isoform of low-voltage-activated or T-type calcium channels (T-channels) in this process. Further experiments are needed to determine whether thalamic T channels could serve as targets for the treatment of OIH.

 Duodenal polyps are rare in patients undergoing upper gastrointestinal endoscopy. The present study is an experience of the histopathological spectrum of the duodenal polyps and its correlation with the clinical and endoscopic findings in a tertiary care centre.

The vestibular/ocular motor screening (VOMS) is a clinically validated screening tool for concussion management. Multiple factors have been known to influence VOMS performance such as preexisting migraine and mood disorders. Poor sleep is an another important variable that warrants investigation as a modifier on the VOMS that may need to be considered during administration.

Introduction Subdural hematoma without subarachnoid hemorrhage secondary to intracranial aneurysm rupture is rare and may complicate patient management due to delay in diagnosis and subsequent treatment. Herein, we describe a case presenting with pure SDH secondary to the rupture of a posterior communicating artery infundibular dilatation (PcoA-ID). To the best of our knowledge, this is the first case of rupture of a PcoA-ID with SDH in the convexity and tentorium, which also tracked into the upper cervical spine along the subdural space. Additionally, we briefly discuss the previously published cases of pure SDH secondary to intracranial aneurysm rupture. Case Report A 44-year-old female presented with headache, dizziness, nausea and left-sided diplopia to an outside institution. Initial diagnostic work-up showed no intracranial hemorrhage, however, magnetic resonance angiography and subsequent digital subtraction angiography revealed left posterior communicating artery infundibular dilatation. Two days later, the patient presented with a loss of consciousness. Computed tomography was positive for bilateral hemispheric subdural hematoma with no evidence of subarachnoid hemorrhage. Digital subtraction angiography showed left posterior communicating artery infundibular dilatation and pseudoaneurysm originating from the inferior area of the infundibular dilatation, concerning recent rupture. Balloon assisted coil embolization was performed and the patient had a good outcome without any neurological deficit. Conclusion Subdural hematoma in a young adult without a history of trauma or coagulopathy warrants additional vascular imaging to search for underlying vascular lesions. It should also be kept in mind that infundibular dilatation may rupture and cause a pure subdural hematoma.

Osteoarthritis is the most common human joint disease in the world. It is also one of the most common skeletal muscle defects, destructive joint changes, and the leading cause of disability and reduced quality of life. Destructive changes in inflammatory joints are associated with a range of biochemical events, including the overproduction of inflammatory cytokines. Cytokines are protein compounds that play an essential role in causing and regulating inflammation. A balance between pro-inflammatory and anti-inflammatory cytokines is crucial in maintaining a stable body. In some inflammatory diseases, including osteoarthritis, the balance between these compounds is disturbed, and the balance shifts to pre-inflammatory cytokines. For this reason, researchers today are trying to find an effective way to reduce inflammation and treat osteoarthritis by using certain compounds. Current treatments for osteoarthritis, including nonsteroidal anti-inflammatory drugs, glucocorticoids, and hyaluronic acid, are mainly based on reducing pain and inflammation. However, they have limited effects in controlling symptoms and improving the patient's quality of life. Also, due to the high level of side effects, synthetic drugs have led to the identification of compounds of natural origin to give patients a chance to use painkillers and anti-inflammatory drugs with fewer side effects. This review study aimed to present the role of quercetin as a natural compound in reducing the expression of pro-inflammatory cytokines in osteoarthritis. This study also discusses the relationship between inflammation and cartilage destruction and other inflammation-related factors caused by cytokines.

New remedies are required for the treatment of diabetic neuropathic pain (DNP) due to insufficient efficacy of available therapies. Here, we used chemogenetic approaches combined with in vivo pharmacology to elucidate the role of basolateral amygdala (BLA) astrocytes in DNP pathogenesis and provide new insights into therapeutic strategies for DNP.

Middle meningeal artery (MMA) embolization is becoming increasingly studied as a safe, effective treatment for chronic subdural hematoma (cSDH) in adults. Among pediatric patients, however, MMA embolization for cSDH has been rarely described, and the potential benefit of this approach for pediatric patients remains unknown.

To develop a patient-centered text message-based platform that promotes self-management of symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS).