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Despite rapid advances in the field of chronic pain, it remains extremely challenging in the clinic. Pain treatment strategies have not improved for decades as opioids remain the main prescribed drugs for chronic pain management. However, long-term use of opioids often leads to detrimental side effects. Therefore, uncovering the mechanisms underlying the development and maintenance of chronic pain may aid the discovery of novel therapeutics to benefit patients with chronic pain. Substantial evidence indicates downregulation of α7 nicotinic acetylcholine receptors (α7 nAChR) in the sciatic nerve, dorsal root ganglia, and spinal cord dorsal horn in rodent models of chronic pain. Moreover, our recent study and results from other laboratories demonstrate that potentiation of α7 nAChR attenuates pain behaviors in various murine models of chronic pain. This review summarized and discussed the preclinical evidence demonstrating the therapeutic potential of α7 nAChR agonists and allosteric modulators in chronic pain. This evidence indicates that potentiation of α7 nAChR is beneficial in chronic pain, mostly by alleviating neuroinflammation. Overall, α7 nAChR-based therapy for chronic pain is an area with great promise, but more research regarding its detailed mechanisms is warranted.

Contrast medium (CM) administration during computed tomography (CT) enhances the accuracy in the detection and interpretation of abnormalities. Evidence from literature also validate the essence of CM in imaging studies. CT, by virtue of its ubiquity, ease of use, speed, and lower financial footprint, is usually the first investigation in cases of headache. Through a multicenter retrospective analysis, we compared findings of contrast-enhanced CT (CECT) to noncontrast-enhanced CT (NCECT) head examinations among patients presenting with headache.

Hypertension is one of the leading causes of morbidity and mortality in Saudi Arabia affecting 31.4% of the population. The Illness Perception Questionnaire-Revised (IPQ-R) is a validated and reliable tool for assessing the perception of hypertension among patients. This cross-sectional study aimed to translate the Revised Illness Perception Questionnaire (IPQ-R) into Arabic and validate it among Arabic patients with hypertension from the outpatient departments of the Prince Sattam University Hospital and King Khalid Hospital (KKH) in Al-Kharj City in the Kingdom of Saudi Arabia.

RRx-001 is a small molecule NLRP3 inflammasome inhibitor with anti-CD47 and antiangiogenic/vascular normalization properties in a Phase 3 clinical trial that has been designated as a drug-device combination by the FDA. In the Phase 1 first-in-man dose escalation clinical trial, where RRx-001 was given by direct intravenous (IV) infusion, the main adverse event was a sterile painful infusion phlebitis (IP). Less pain was experienced when RRx-001 was infused at a slower rate over multiple hours which was impractical on an outpatient basis. In Phase 2, for reasons of convenience and safety, RRx-001 was co-administered with an aliquot of autologous blood from an device called the eLOOP on the premise that RRx-001 binds to hemoglobin on red blood cells (RBCs), making it unavailable to directly interact with venous nociceptors. Phlebitis has the potential to progress to deep venous thrombosis or septic thrombophlebitis or post-thrombotic syndrome in hypercoagulable and immunosuppressed cancer patients. In this 13-week toxicology study of once weekly IV RRx-001 administration to Wistar Han rats followed by a recovery period of 28 days. The main observed toxicity was a significant inflammatory response in the vein wall, consistent with superficial venous thrombosis observed in man. Due to this development, direct IV infusion of RRx-001 is relatively contraindicated in favor of co-administration with autologous blood.

The chronic pain and functional limitations in osteoarthritis (OA) patients can increase risk of psychiatric disorders, e.g., major depression disorder (MDD), which may further aggravate the clinical symptoms of OA. Early detection of MDD is essential in the clinical practice of OA.

Locoregional interventional therapy including transcatheter arterial chemoembolization (TACE) and ablation are the current standard of treatment for early-to-mid-stage hepatocellular carcinoma (HCC). However, questions remain unanswered regarding the management of recurrence after locoregional treatment. PD-1 inhibitors can block inhibitory signals of T-cell activation and proliferation to reduce the recurrence. We conducted a single-arm phase 2 trial to evaluate the efficacy and safety of PD-1 inhibitors following locoregional interventional therapy in HCC patients with high recurrence risk guided by our novel scoring system.

We report a rare case of a patient with cystic fibrosis suffering from debilitating abdominal pain due to chronic pancreatitis. This 13-year-old patient was evaluated for surgical intervention to relieve pain from chronic pancreatitis and to improve quality of life. The patient carried two mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; the most common ΔF508 variant and a second variant, p.Glu1044Gly, which has not been previously described. The patient's condition did not improve despite medical management and multiple endoscopic interventions, and therefore total pancreatectomy with islet autotransplantation and a near-total duodenectomy was offered for definitive management. Patient-derived duodenal crypts were isolated and cultured from the resected duodenum, and duodenal organoids were generated to test CFTR function. Our studies demonstrate that this novel mutation (ΔF508/p.Glu1044Gly) caused severely impaired CFTR function . The Food and Drug Administration (FDA)-approved drug ivacaftor, a CFTR potentiator, was identified to robustly improve CFTR function in the context of this novel mutation. Herein, we describe a personalized medicine approach consisting of performing drug testing on individual patient derived organoids that has potential to guide management of patients with novel CFTR genetic mutations. Identified effective medical therapeutics using this approach may avoid irreversible surgical treatments such as total pancreatectomy with islet autotransplantation in the future.

Orofacial pain, in particular, chronic orofacial pain remains a great challenge in clinical practice. To better understand the underlying mechanism of disease, it is essential to apply a feasible and stable preclinical measurement of facial pain. Here, we introduced a novel electrical noxious stimulator in freely behavioral rodents and examined its validation in both naïve and chronic orofacial pain animals.

Pruritus of chronic spontaneous urticaria (CSU) is one of the most common and irritating sensations that severely affects the quality of life. However, the changes in the functional connectivity (FC) between thalamic subregions and other brain regions have not been fully elucidated. This study aimed to explore the potential changes in brain neural circuits by focusing on various subregions of the thalamus in patients with CSU pruritus to contribute to the understanding of chronic pruritus from the perspective of central mechanisms. A total of 56 patients with CSU and 30 healthy controls (HCs) completed the data analysis. Urticaria Activity Score 7 (UAS7), pruritus visual analog score (VAS-P), Dermatological Life Quality Index (DLQI), and immunoglobulin E (IgE) values were collected to assess clinical symptoms. Seed-based resting-state functional connectivity (rs-FC) analysis was used to assess relevant changes in the neural circuits of the brain. Compared to HCs, seeds within the caudal temporal thalamus (cTtha) on the right side of patients with CSU showed increased rs-FC with the cerebellum anterior lobe (CAL). Seeds within the lateral prefrontal thalamus (lPFtha) on the right side showed increased rs-FC with both CAL and pons, while those within the medial prefrontal thalamus (mPFtha) on the right side showed increased rs-FC with both CAL and the dorsal lateral prefrontal cortex (dlPFC) on the right side. Seeds within the posterior parietal thalamus (PPtha) on the right side showed increased rs-FC with the cerebellum posterior lobe (CPL) on the left side. The UAS7 values and IgE levels were positively correlated with the rs-FC of the right dlPFC. Our results suggest that patients with CSU may exhibit stronger rs-FC alterations between certain thalamic subregions and other brain regions. These changes affect areas of the brain involved in sensorimotor and scratching.

Cerebrovascular involvement of Kawasaki disease (KD) is poorly studied. White matter hyperintensities (WMH) indicate cerebral small vessel disease and increase the risk for stroke.